[Frontiers in Bioscience S3, 1390-1406, June 1, 2011]
Origin, maturation and recruitment of mast cell precursors
Maria Celia Jamur1, Constance Oliver1
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TABLE OF CONTENTS
1. ABSTRACT
Mast cells have gained increased recognition as immunomodulators playing a role in a variety of physiological and pathological processes. They were first described in 1879, but their origin remained controversial for almost a century. Today, it is known that mast cells are present in the bone marrow as committed mast cell precursors. They leave the bone marrow as progenitors and complete their maturation at peripheral sites. Investigations on the maturation of bone marrow derived mast cells focused on bone marrow cultured in the presence of interleukin-3 (IL-3) and stem cell factor (SCF). SCF is essential for mast cell survival and mice that lack either SCF or the receptor for SCF are mast cell deficient. It is the microenvironment surrounding the mast cell that determines its mature phenotype. SCF, IL-3 and IL-9 have been identified among the most important cytokines for regulation of mast cell growth and differentiation. Several factors have been identified as chemoattractants for mast cells, but their exact mechanism of action remains unclear. Mast cell recruitment is most likely a combination of the direct effect of mast cell mediators on the mast cell progenitor as well as the indirect effect of these mediators on other cell types.
2. INTRODUCTION
Mast cells (Figure 1) have long been known to play a pivotal role in inflammatory and allergic reactions (1-3). Recently they have gained increased recognition as immunomodulators playing a role in a wide variety of physiological processes (4-8). Mast cells respond to stimuli of innate and adaptive immunity with the immediate and delayed release of inflammatory mediators. Due to their ability to instantly release a wide variety of mediators, mast cells are essential for optimal responses during inflammatory processes (9, 10). Mast cells also direct the development of Th2 responses to allergens, especially when exposure occurs simultaneously with exposure to pathogens and their products (11-13). In addition to allergy and inflammation, mast cells have been shown to be involved in a number of normal and pathological conditions including wound healing, tissue remodeling, cancer, diseases of the nervous and cardiovascular systems, and autoimmune diseases (5, 6, 9, 14-17). Mast cells are located in connective tissue at the interface between the host and the environment and under normal conditions their numbers remain relatively constant. Mast cell numbers increase during hypersensitity reactions, infections, and in response to various disease processes (7). During recruitment, mast cells are thought to leave the bone marrow as progenitors and migrate to peripheral sites where they complete their maturation (1, 18). It is the microenvironment surrounding the mast cells that determines their mature phenotype. Two types of mature mast cells, mucosal mast cells (MMC) and connective tissue type mast cells (CTMC), have been described for rodents and humans (19-22). The specific homing mechanism that leads to mast cell recruitment is poorly understood and much still remains to be learned about mast cell development and recruitment.
3. ORIGIN OF MAST CELL COMMITTED PRECURSORS
Although mast cells were first described by Paul Erlich in 1879 (23), their origin remained controversial for almost a century. Several possible candidates for mast cell precursors were suggested, among them mesenchymal cells, lympohocytes, macrophages, mononuclear phagocytes and myeloid cells (24, 25). Because of their association with connective tissue, it was initially suggested that mast cells were derived from primitive mesenchyme (26, 27). Other studies have suggested that mast cells could be derived from lymphocytes (28). In the gut, a novel type of granulated lymphocyte was described that was thought to have the ability to differentiate into mast cells (29). The presence of both macrophages and mast cells was noted in soft agar cultures of rat peripheral blood suggesting that mast cells and macrophages may have a common precursor (30). Other in vitro studies using rat peritoneal exudates also suggested that mononuclear phagocytes give rise to mast cells (31-33).
The pioneering work of Kitamura et al. (34) in 1977 was the first to demonstrate that tissue mast cells are derived from bone marrow precursors. Normal C57Bl (+/+) mice and Beige (C57Bl BgJ/BgJ) mice which have large, easily distinguished, abnormal mast cell granules (35) were used in this study. When bone marrow from Beige mice was grafted into irradiated normal C57Bl mice, it took approximately 40 days for the donor mast cells to appear in the tissue of the host animal. This suggested that the mast cells found in the host tissues are derived from precursors from the donor bone marrow. This hypothesis was further strengthened by subsequent experiments using W/WV mice (36). Russell (37) extensively reviewed the available literature on both W*/W* and Sl*/Sl* mutant mice and concluded that the W locus encodes a receptor expressed by the affected cells in the W*/W mice. Examination of various tissues revealed that the W/Wv mice were deficient in mast cells and that this mast cell deficiency could be corrected by bone marrow transplantation from wild type mice. On closer examination of the mast cell distribution in the transplanted W/WV, it appeared that, especially in the skin and mesentery, the mast cells may be developing in clusters. In order to test the possibility that these mast cell groups were clonal in nature, W/Wv mice were injected with a mixture of bone marrow cells from Beige and normal C57Bl mice. When the resulting clusters of mast cells were examined over 95% of the clusters consisted of either Beige-type mast cells or normal-type mast cells. These results indicated that the mast cell clusters were clonal in nature being derived from a single bone marrow derived mast cell precursor (38). Additional studies demonstrated that in comparison to the bone marrow, the thymus, lymph node, and Peyer's patch have less than 0.1% of the number of mast cell precursors. Furthermore, T lymphocytes and the thymus are not essential for precursor differentiation into mature mast cells (39).
Other investigations examined the maturation and function of tissue resident mast cell precursors using various in vitro methods. Early studies focused on mast cells derived from rat and mouse thymus (40-43) and mouse lymph nodes (44). Mast cell suspensions were prepared from the thymus or lymph nodes, plated onto embryonic fibroblast feeder layers and cultured in medium supplemented with horse serum. Under these conditions it was possible to establish long-term cultures of clonally derived mast cells that contained metachromatic granules and bound IgE. When lymph nodes were obtained from mice that had been immunized with horse serum and then cultured on embryonic skin-derived feeder layers in the presence of horse serum, the differentiation of the mast cells was more complete (45). Moreover, two types of mast cell clones could be identified in these cultures, one originating from the lymphoid tissue and the other from the embryonic skin monolayer (24). The mast cells originating from precursors in the lymph node and thoracic duct cell suspensions have the characteristics of MMC (46). While the mast cells arising from embryonic skin fibroblast monolayers have the characteristics of CTMC. These studies demonstrated that mast cell progenitors (MCp) for both MMC and CTMC exist in the peripheral tissues could develop into mature mast cells in vitro.
In the course of investigating the development of mature mast cells from rat peritoneal exudates, it was reported that spleen and bone marrow also contain MCp that are capable of maturing into mast cells in vitro (32), thus confirming the in vivo results of Kitamura (34, 39, 47) showing that the bone marrow is the major source of MCp. With the ability to culture bone marrow derived mast cells the search for the mast cell committed precursor (MCcp) accelerated (25). The capacity to successfully culture bone marrow derived mast cells independent of feeder layers, depended upon the addition of factors to the media that specifically simulated growth and differentiation of mast cells. In 1981, several groups described media supplements that supported growth of pure mast cell populations. Cloned Ly1+2- inducer T cells produced a factor that selectively supports the growth and differentiation of mouse mast cells from hematopoetic tissue (48). Addition of WEHI-3 conditioned medium to mouse bone marrow cultures permitted the establishment of non-adherent mast cell lines (49). Growth of mouse bone marrow cells with conditioned medium from pokeweed mitogen- or Concanavalin A-stimulated splenocytes also yielded a pure population of mast cells (50-53). These cells were termed P cells because of their persistent growth in liquid culture (51). The cells that arose with culture in conditioned medium from Concanavalin A-stimulated splenocytes were characterized and considered to be mucosal mast cells (MMC) (54).
Attention then turned to identifying the exact nature of the growth factor(s) that were responsible for mast cell survival and differentiation in mouse bone marrow cultures (Figure 2.). Initial attempts to characterize these factors identified a mast cell growth factor (MCGF) in conditioned medium from Concanavalin A-stimulated splenocytes (55). While this factor was distinct from T cell growth factor its relationship to granulocyte colony-stimulating factor (G-CSF) remained unclear. Further characterization revealed that MCGF was a separate and distinct growth factor from G-CSF (56). P cell stimulating factor (PSF) was also isolated from T lymphocytes and PSF and MCGF were found to share many similar properties. MCGF was purified from Concanavalin A-stimulated splenocytes and termed interleukin-3 (IL-3) (57). Since the WEHI-3 cell line was found to constitutively produce IL-3 at levels that were 100 times those seen with Concanavalin A-stimulated splenocytes (58), WEHI-3 conditioned medium was used to purify IL-3 to homogeneity (59). The purified IL-3 gave the same dose-response curve as WEHI-3 growth factor, MCGF and P cell stimulating factor (60), indicating that IL-3 was responsible for the biological activities of the other factors. Murine IL-3 was subsequently cloned (61). In cultures of murine bone marrow IL-3 supports the growth of almost all hematopoetic lineages (62-64). Although IL-3 would support the growth of MMC in vitro another factor, IL-4, was necessary to support the growth of CTMC (65, 66). The other growth factor that is essential for maintaining mast cell colonies in vitro is stem cell factor (SCF) (67). Russell (37) also examined the data available for the Sl*/Sl* mutant mice and concluded that that the Sl locus encodes for the ligand and that the receptor is encoded by the W locus. SCF or c-kit ligand binds to the c-kit receptor on mast cells and other hematopoetic cells (68-76) and induces mast cell proliferation in vitro (77-80). In primates injection of SCF resulted in the expansion in the number of mast cells at many sites. When administration of SCF was stopped, the number of mast cells returned to normal. Again, indicating a critical role for SCF in regulation of the mast cell population in vivo (81).
3.1. Mouse bone marrow derived mast cell committed precursor
The identification of IL-3 as a growth factor for mast cells stimulated the search for a MCcp. In liquid cultures of mouse bone marrow supplemented with IL-3, after 7 days mast cells and granulocytes were the predominant cell types (82). In another set of experiments, at one week approximately one third of the cells now have receptors for IgE (63, 64) and by 3 weeks all of the cells in the culture had IgE receptors. By electron microscopy the cells had a typical mast cell morphology (64). In vitro velocity sedimentation and buoyant density studies further suggested that the mast cell precursors are low density cells (82). Flow cytometry investigation of surface markers showed that there were transient subpopulations of Thy1.2 positive cells that also expressed IgE receptors, CR3 receptors or neither receptor. The data from this study suggested a differentiation pathway in which the Thy 1.2 positive precursor cells give rise to granulocytes and mast cells (83). In mouse IL-3 dependent bone marrow cultures, transcripts for high-affinity receptor for immunoglobulin E (FcεRI) subunits as well as the membrane receptors are present by 1 week of culture (84). These cells do not have granules, and have few morphological characteristics of mature mast cells. With time in culture, there is an increase in the number of FcεRI positive mast cells, and an increase in the expression of FcεRI subunits, as well as an increase in histamine content. Agarose cultures at one week showed that the majority of the cells were MCp (25). It was further noted that various cytokines could influence mast cell maturation. When BMMC were cultured in the presence of rIL-3 with or without SCF, the cells did not stain with safranin and produced virtually no 35S-labeled heparin proteoglycans. They did, however, contain higher levels of mouse MC protease (MMCP)-5 mRNA and mast cell carboxypeptidaseA (MC-CPA) mRNA than MNCP-6 mRNA. In contrast BMMC cultured in the presence of rSCF alone or in a sequential culture, first with rSCF followed by IL-3 expressed high levels of MMCP-4 and MMCP-6 mRNA as well as transcripts that encoded MMCP-5 and MC-CPA (85). Additional studies with BMMC showed that IL-10 could modify the expression of MMCP-2 (86) and that IL-4 synergistically enhanced the growth of mast cells when IL-3 was present (87, 88). Taken together, these results demonstrated that the MMC phenotype is not fixed, but is dynamic and appears to be regulated by the cytokines present in the various microenvironments surrounding mast cells.
Although these in vitro studies pointed to the existence of a MCcp in the bone marrow, it remained difficult to identify. A MCp was identified in fetal mouse blood at only 15 days of gestation (89). This promastocyte was Thy-1lo, c-kithi, FcεRIneg, contained cytoplasmic granules, and expressed mRNA for MC-CPA, MCP-2 and MCP-4. Using sequential immuno-isolation with two mast cell specific antibodies (mAb AA4 and mAb BGD6), Jamur et al. (90) were successful in purifying a MCcp from the bone marrow of Balb/c mice (Figure 3). These undifferentiated cells were small with a large nucleus, little cytoplasm and no cytoplasmic granules. The cells were CD34+, CD13+, and c-kit+. The MCcp were negative for Sca-1, Ly-6G/Ly-6C, CD11b (Mac-1), Thy-1, CD40, CD45R/B220 and FcεRI. However, they did contain message for the α and β subunits of FcεRI, mouse-MCP-5, mouse-MCP-7 and mouse-CPA. When the MCcp were cultured in the presence of SCF and IL-3 they gave rise only to mast cells. Moreover, these cells had the ability to reconstitute the mast cell population in lethally irradiated mice. This and additional studies have shown that mAb BGD6 is a lineage marker for mast cells (18, 91). Using FACS analysis Chen et al. (92) identified a MCcp in adult C57BL/6 mouse bone marrow that was Lin-, c-Kit+, Sca-1-, Ly6c-, FcεRIα-, CD27-, β7+ and T1/ST2+. These cells gave rise only to mast cells in culture and could reconstitute mast cells in C57BL/6-KitW-sh/KitW-sh c-kit mutant mast cell-deficient mice. These authors further suggested that the MCcp is derived directly from multipotential progenitors in the bone marrow. The MCcp isolated from mice (90, 92) has many of the same characteristics as the MCcp previously described in human bone marrow (93).
3.2. Human Bone marrow derived mast cell committed precursor
The identification of a MCcp from human bone marrow was stimulated by the finding that mouse bone marrow cultured in the presence of IL-3 gave rise to mast cells (60). However, in initial attempts to culture human bone marrow in liquid cultures with IL-3, the bone marrow gave rise to basophils (94). By modifying the culture conditions, it proved possible to culture mast cells from human bone marrow on the interface between soft agar and liquid medium supplemented with human rIL-3 (95, 96). Further studies showed that when bone-marrow derived CD34+ cells were cultured in liquid culture in serum free medium in the presence of rhIL-3, rhIL-6 and rhSCF they gave rise to mast cells, thus indicating that the bone-marrow derived mast cell precursor is CD34+/c-kit+ (97). It was also observed that CD13 is expressed on the surface of rodent mast cells (98), on cultured human mast cells from liver (99) as well as being expressed at several different stages of myeloid differentiation (100). When FACS sorted CD34+/c-kit+/CD13+ cells were cultured in the presence of various cytokines only mast cells and monocytes grew from this population, indicating that the human MCcp was included in a population of cells that was CD34+/c-kit+/ CD13+(93). The human MCcp was similar to the MCcp identified in murine bone marrow (90, 92). The cells were lymphoid-like, had a large nucleus, little cytoplasm, no cytoplasmic granules and were FcεRI negative.
4. MAST CELL MATURATION
4.1. Maturation of mast cells at peripheral sites
Identification of mast cells in the early stages of maturation, especially in vivo, has been limited (101), and the process of mast cell differentiation and maturation is still poorly understood (102, 103). The majority of the studies to date on mast cell maturation have been done with experimental animal models (104-106), or in young animals (107, 108). The majority of in vivo studies on mast cell maturation have relied on the presence of granules or granule content to identify the stage of mast cell maturation (101). However, cytoplasmic granules are not present in sufficient quantity in the very immature mast cells to permit their use as an identifying characteristic. A number of previous investigations have attempted to use antibodies to identify immature mast cells, but their usefulness has been limited due to the fact that these antibodies were not mast cell-specific and recognized other cell types in the preparation. Another limitation of the use of antibodies to detect granule contents in immature mast cells is that the immature cells do not yet express the full complement of granule components (103). By immunoelectron microscopy, using antibodies that mark the mast cell surface (109), it was possible to characterize a very immature mast cell containing only one or two small cytoplasmic granules that is positive for both FcεRI and binds IgE (110). It is likely that these very immature cells represent MCp. These MCp appeared to have the same morphological characteristics as small lymphocyte-like cells previously reported to be MCp (110-113).
4.2. Maturation of bone marrow derived mast cells
The initial differentiation of MCcp is presumed to occur in the bone marrow. However, few studies have examined the maturation of mast cells in the bone marrow. Initial investigations focused on the culture of mouse or human bone marrow in the presence of growth factors, especially IL-3 and SCF. Using bone marrow cultures enriched for hematopeotic progenitors cultured in the presence of IL-3 and SCF, it was demonstrated that the expression of FcεRI on the mast cell surface occurs at about 3 days in culture and is correlated with the initiation of secretory granule formation (112, 114). When murine bone marrow cells were cultured in the presence of IL-3 for 1 week, the cells contained few, if any, granules, but they did contain transcripts for FcεRI subunits and the majority of the cells bound IgE. However, only 25% of the cells could be recognized as mast cells. The expression of transcripts and the number of receptor-positive cells continued to increase with time in culture. This was accompanied by a progressively larger number of cells that were granulated and by week 3 ~90% of the cells could be recognized morphologically as mast cells (25, 84).
Using the mast cell specific mAb AA4 as well as panel of other antibodies it has been shown that mast cells can completely differentiate in the bone marrow into connective tissue-type mast cells (Figure 4) (115). The stages of maturation of the bone marrow-derived mast cells agree with those described for other granulocytes in the bone marrow (116-119). In addition to the MCcp, three distinct stage of mast cell maturation, very immature, immature, and mature, were seen in the bone marrow. The very immature mast cells contained few granules and would not be recognized as mast cells without the use of specific cell surface markers. Pure populations of mast cells were also isolated from the bone marrow using mAb AA4-conjugated magnetic beads. The same three stages of maturation that were seen in the unfractionated bone marrow could be identified in the isolated mast cell population. All of the cells were α subunit-FcεRI+, c-kit+ and bound IgE, thus confirming their identity as mast cells. By flow cytometry, mast cells represent approximately 2.4% of the cells in the bone marrow. Staining with toluidine blue and berberine sulfate, as well as RT-PCR indicated that the mast cells are connective tissue-type mast cells. Therefore, all of the factors necessary for mast cell maturation are present in the bone marrow. These studies have indicated that mast cell maturation in the bone marrow occurs with the same sequence as that seen at peripheral sites, such as the peritoneal cavity (105, 106).
4.3. Major factors affecting mast cell proliferation and maturation
The microenvironment surrounding a mast cell determines its mature phenotype (62, 120). In many of the early studies, the cultures were mixed consisting mainly of mast cells and macrophages. Thus, contradictory findings for a given cytokine may result from the fact that in response to the cytokine, macrophages were producing other factors that act on mast cells. In the microenvironment, SCF, IL-3, and IL-9 have been identified among the most important cytokines for regulation of mast cell growth and differentiation (121-124). The most critical requirement for mast cell growth and maturation is the ligand SCF secreted by fibroblasts, stromal cells and endothelial cells, and its receptor c-kit (CD117) on the mast cell itself (125). This was clearly shown in SCF deficient mice such as WCBF1-KitSl/KitSl-d (Sl/Sld) (126, 127) and in c-kit deficient mice such as WBB6F1-kitW/KitWv (W/Wv) (36, 69, 75). As demonstrated by many studies (see section 3), SCF is also required for survival of mast cells in vitro. Other cytokines and growth factors in combination with SCF can also modulate mast cell maturation. IL-3 has been shown to play a key role in the survival and development of mast cells from mouse bone marrow (128-130) and either SCF or IL-3 alone can support diffentiation of mast cells from unfractionated mouse bone marrow (60, 85). In cultures of human mast cells IL-3 as well as IL-4 also promotes mast cell survival (131, 132). In murine bone marrow cultures IL-4 in the presence of SCF induced the differentiation of CTMC (133). IL-4 also acts synergistically with IL-3 to promote murine mast cell growth and survival (128, 129). However, culture of mouse bone marrow derived and peritoneal mast cells in the presence of IL-3, IL-4 and IL-10 leads to apoptosis (134). In isolated human intestinal mast cells IL-4 in combination with SCF promoted mast cell proliferation and induced the expression of Th2-type cytokines (IL-3, IL-5 and IL-13) (135). IL-4 attenuated the number of mast cells, especially the population that expressed only tryptase in cultures of human fetal liver-derived mast cells (136). IL-5 has also been shown to influence human mast cell proliferation and maturation (93, 132). IL-6 has been shown to stimulate development of splenic mast cells (137). IL-6 in combination with SCF and IL-10 was also able to induce the development of a MCp from bone marrow (138). In cultures of human mast cells, depending on the subset of mast cells, IL-4 inhibits mast cell growth and differentiation (136, 139, 140) and may lead to apoptosis (141). IL-6 has also been shown to prolong survival and to stimulate mast cell growth in the presence of SCF (93, 131, 132, 142-145) and can protect mast cells from apoptosis induced by IL-4 (141). In contrast, in cultures of CD34+ SCF derived mast cells from human cord blood IL-6 inhibited mast cell growth and the reduced the expression of c-kit (146). However, in another study, human mast cells derived from cord blood proliferated and matured in the presence of SCF, IL-6 and IL-10 (132). In vitro IL-9 can also act as a potent mast cell growth factor in murine and human systems, alone or in synergy with IL-3 (147, 148). IL-9 transgenic mice that over express IL-9 displayed an infiltration of both MMC and CTMC in the gut, trachea and kidney (122). IL-10 is another co-factor that in combination with SCF stimulates mast cell proliferation (129, 149, 150). However, IL-10 also inhibits IL-6 production (151), and reduces the surface expression of FcεRI (150, 152). On the other hand, cultures of total murine bone marrow with SCF, IL-3 and IL-10 leads to mast cell apoptosis (153). Limited studies have been done on the effect of IL-13 on mast cells. When IL-13 is added to human lung mast cells cultured in the presence of SCF, IL-6 and IL-10, mast cell proliferation and FcεRI expression increased (154). In murine mast cells IL-13 in the presence of IL-4 can also stimulate mast cells proliferation (124). IL-15 (155, 156) and IL-16 (157) both increase the proliferation of mast cells in conjunction with other cytokines.
In addition to the cytokines cited above various other factors can affect mast cell growth and differentiation. Using both in vitro and in vivo systems, nerve growth factor (NGF) has been shown to induce murine mast cell development, survival and function (158-160). In vitro in the presence of NGF, murine mast cells up regulate mast cell specific characteristics such as FcεRI, histamine and tryptase (161). NGF also induces the differentiation of CTMC in the presence of IL-3 (162). In murine peritoneal mast cells NGF prevents apoptosis of the mast cells (163) and NGF in combination with SCF prevents apoptosis in human cord blood derived mast cells (164). Tumor necrosis factor-α (TNF-α) is important for mast cell survival and differentiation both in vitro and in vivo (137, 165). Transforming growth factor-β (TGF-β) has both stimulatory and inhibitory effects on mast cells. It inhibits proliferation and induces apoptosis in both human and murine mast cells (166-174) while under other conditions it can have a stimulatory effect, promoting murine MMC development (175, 176) and the transcription of mast cell proteases (177, 178). Activin A, a member of the TGF-β superfamily, in a dose dependent fashion stimulated the differentiation of MCp into mature mast cells (179). Thrombopoeitin (TPO) also has differential effects in human and murine mast cells. The effect on human mast cells is to induce mast cell development (180, 181), while TPO inhibits differentiation in murine mast cells (182, 183). Further studies have shown that TPO is important in selectively increasing dermal mast cells as compared to mucosal mast cells (184). Other cytokines such as interferon-γ (IFN-γ) (132, 185, 186), granulocyte-macrophage-colony stimulating factor (GM-CSF) (144, 187) and retinoic acid (188-190) all inhibit mast cell proliferation.
5. MAST CELL RECRUITMENT
There are two distinct steps in mast cell recruitment that must be considered. First is the recruitment of MCp/MCcp from the bone marrow into the circulation and second is the exit of mast cells from the circulation into peripheral tissues where they mature (Figure 5). Because of the lack of markers that could distinguish between the MCp and the MCcp it was unclear which cell was actually recruited to peripheral sites. Recently, using mast cell specific markers that distinguish between the MCp and MCcp, it was demonstrated that it is the MCp and not the MCcp that is present in the circulation and is responsible for repopulation of peripheral sites (18). Using osmotic lysis of peritoneal mast cells by distilled water (104, 106), twenty-four hours after intraperitoneal injection of distilled water no mast cells were present in the peritoneal lavage and only a few mast cells could be seen in the mesentery, near adipose tissue. At 12 hours after i.p. injection of distilled water MCp could be isolated from the blood, and by 48 hours could be identified in mesenteric blood vessels. During this time the percentage of MCcp increased in the bone marrow. During infection with the intestinal nematode Trichinella spiralis there is a loss of MCp that are c-kit+/β7+ from the bone marrow that correlates with their appearance in the blood and their appearance 3 days after infection in the gut (191). Additionally, at least a portion of the repopulation of the mesentery and peritoneal cavity can be attributed to mitosis of MCp(18).
In order to repopulate peripheral sites, MCps must leave the bone marrow. Although the exact mechanism(s) by which this occurs remain to be elucidated, the initial steps appear to be recruitment of MCp by adhesion to the microvascular endothelium and transport via the circulatory system (18) to peripheral sites. Rodent mast cells express α4, β1 and β7 integrins (192). The importance of β7 integrin for mast cell recruitment to the small intestine during helminth infection was demonstrated using knockout mice for β7 integrin (193). The homing of MCp to the small intestine proved to be dependent upon the interaction of α4β7 integrin with the mucosal addressin cellular adhesion molecule-1(MAdCAM-1) (194). This homing of MCp to the small intestine relied on the presence of CXC chemokine receptor 2 (CXCR2) and on vascular cell adhesion molecule-1 (VCAM-1). Mice deficient in the chemokine receptor CXCR2 also have reduced numbers of intestinal MCp, suggesting that chemokines, such as CXCL1 (KC) and CXCL2 (MIP-2), are involved in MCp trafficking (195, 196). In the lung, VCAM-1 interactions with both α4β1 and α4β7 integrins are essential for MCp recruitment and expansion during antigen-induced pulmonary inflammation (197) CXCR2 appears to regulate endothelial VCAM-1 expression, MCp migration, as well as the level of intraepithelial MCp in the lungs of aerosolized, antigen challenged mice (198). Mac-1(CD11b/CD18, CR3) a β2 integrin has also been shown to be required for normal levels of mast cells in the peritoneal cavity, peritoneal wall, and certain areas of the skin (199).
Although several factors have been identified as chemoattractants for mast cells their exact mechanism of action remains unclear (6). Mast cell recruitment to peripheral sites is most likely a combination of the direct effect of the release of mast cell mediators on the MCp itself as well as the indirect effect of these mediators on the activation of other cell types. These other cells can then also release mediators that have chemoattractant activity for mast cells (6, 200-203). One of the most potent chemoattractants for mast cells is TGF-β1 (204-207). TGF-β1 is stored in mast cell granules in an inactive form and upon release it is activated by cleavage with chymase 1 which is also stored in mast cell granules (208). Another member of the TGF-β superfamily, Actinvin A, also induces migration of MCp (179). Leukotriene B4 obtained from activated mast cells also induces pronounced mast cell chemotaxis (209, 210) in immature, but not mature mast cells. Other eicosanoids, such as prostaglandin E2 may also be involved in mast cell migration, but are effective at a different stage of maturation (211). SCF which is critical to mast cell survival (see section 3) is also known to be an important chemotactic factor for mast cells, especially for MCp (125, 212-215) and its action is potentiated by IL-3. IL-3 alone is also a chemoattractant for mast cells (215, 216).The CC chemokine Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) has also been well characterized as a mast cell chemotatic factor that has pathological implications especially in asthma (205, 217-221). Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-lα (MIP-l) and platelet factor-4 (PF-4) were also shown to be chemotactic for mast cells (221). While RANTES and MCP-1 had potent chemotactic activity on both IgE activated and unactived cells, PF-4 and MIP-1α were chemotactic for IgE activated cells. Tumor necrosis factor (TNF) is another potent chemotactic factor for mast cells (218). In rat peritoneal mast cells the response was biphasic. At lower concentrations, there was significant mast cell migration, but at higher concentrations, migration was inhibited. NGF has been shown to induce chemotactic movement of peritoneal mast cells in a dose dependent manner (222). Chemokine receptors also play a role in mast cell migration. The presence of CXCR2 on the surface of human mast cells is necessary for the mast cell migratory response to IL-8 (223). CXCR3 has also been shown to be important for the migration of lung mast cells in response to chemokines secreted by airway smooth muscle cells in asthmatic patients (224). The anaphylatoxins C3a and C5a are also capable of inducing mast cell migration (225). Serum amyloid A (SAA), an acute-phase protein, has been shown to induce mast cell migraton through a pertussis toxin-sensitive signal transduction pathway (226). Canine mast cells can be activated by C Reative Protein (CRP) in a G-protein mediated activation (227). The human cathelicidin-derived antibacterial peptide, LL-37 has been shown to induce mast cell chemotaxis through specific receptors coupled to the G protein-phospholipase C (PLC) signalling pathway (228). The same group also demonstrated that human β-definsin-2 (hBD-2) also induced mast cell migration by binding to specific receptor(s) that are coupled to G protein-phospholipase signaling (229). Laminin, a component of the extracellular matrix, has also been shown to have chemotactic properties for mast cells. The chemotaxis of mast cells for laminin increases when the cells are activated via FcεRI (230).
6. CONCLUSIONS
While mast cells were first described over a century ago, they remained an enigma until recently. Today, they have taken center stage as an immunomodulator and are assuming an increasingly important role in many disease processes. It is now known that MCcp originate directly from multipotential progenitors in the bone marrow. It is the MCp not the MCcp that leaves the bone marrow to repopulate peripheral sites. The microenvironment at the peripheral site determines the phenotype of the mature mast cell. Many of the factors required for mast cell development, maturation and recruitment have been identified, at least in vitro. In vivo, the interaction of mast cells with other cells makes these processes much more complicated. Additional research is needed to characterize mast cell physiology both in vitro and especially in vivo. A greater understanding of the maturation, recruitment and function of mast cells will lead to the development of new therapeutic strategies for controlling mast cell function.
7. REFERENCES
1. J Hallgren, MF Gurish: Pathways of murine mast cell development and trafficking: tracking the roots and routes of the mast cell. Imunnological Reviews 217, 8-18 (2007) 51. J Schrader: In in vitro production and cloning of the P cell, a bone marrow-derived null cell that expresses H-2 and Ia-antigens, has mast cell-like granules, and is regulated by a factor released by activated T cells. J Immunol 126, 452-458 (1981) 101. AM Dvorak: Basophil and mast cell degranulation and recovery. Plenum Press (1991) 151. JS Marshall, I Leal-Berumen, L Nielsen, M Glibetic, M Jordana: Interleukin (IL)-10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells. J Clin Invest 97, 1122-1128 (1996) 201. P Martin, SJ Leibovich: Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 15, 599-607 (2005) Key Words: Send correspondence to: Maria Celia Jamur, Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade de Medicina de Ribeirao Preto, FMRP-USP, Av. Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brasil, Tel: 55-16-3602-3217, Fax: 55-16-3633-1786, E-mail:mjamur@fmrp.usp.br
doi:10.1111/j.1600-065X.2007.00502.x
PMid:17498048
2. C Liu, Z Liu, Z Li, Y Wu: Molecular regulation of mast cell development and maturation. Molecular Biology Reports 37, 1993-2001 (2010)
doi:10.1007/s11033-009-9650-z
PMid:19644767
3. M Castells: Mast cell mediators in allergic inflammation and mastocytosis. Immunol Allergy Clin N Am 26, 465-485 (2006)
doi:10.1016/j.iac.2006.05.005
PMid:16931289
4. M Maurer, T Theoharides, RD Granstein, SC Bischoff, J Bienenstock, B Henz, P Kovanen, AM Piliponsky, N Kambe, H Vliagoftis, F Levi-Schaffer, M Metz, Y Miyachi, D Befus, P Forsythe, Y Kitamura, S Galli: What is the physiological function of mast cells? Experimental Dermatology 12, 886-886 (2003)
doi:10.1111/j.0906-6705.2003.0109a.x
PMid:14719507
5. G Krishnaswamy, J Kelley, D Johnson, G Youngberg, W Stone, SK Huang, J Bieber, DS Chi: The human mast cell: functions in physiology and disease. Front Biosci 6 D1109 - D1127 (2001)
doi:10.2741/krishnas
PMid:11532608
6. KN Rao, MA Brown: Mast Cells. Multifaceted immune cells with diverse roles in health and disease. Ann. N.Y. Acad. Sci. 1143, 83-104 (2008)
doi:10.1196/annals.1443.023
PMid:19076346
7. KD Stone, C Prussin, DD Metcalfe: IgE, mast cells, basophils, and eosinophils. Journal of Allergy and Clinical Immunology 125(2, Supplement 2), S73-S80 (2010)
doi:10.1016/j.jaci.2009.11.017
PMid:20176269
8. TC Moon, CD St Laurent, KE Morris, C Marcet, T Yoshimura, Y Sekar, AD Befus: Advances in mast cell biology: new understanding of heterogeneity and function. Mucosal Immunol 3, 111-128 (2009)
doi:10.1038/mi.2009.136
PMid:20043008
9. SN Abraham, AL St. John: Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 10, 440-452 (2010)
doi:10.1038/nri2782
PMid:20498670
10. NN Trivedi, GH Caughey: Mast Cell Peptidases: Chameleons of innate immunity and host defense. Am. J. Respir. Cell Mol. Biol 42, 257-267 (2010)
doi:10.1165/rcmb.2009-0324RT
PMid:19933375
11. AM Hofman, SN Abraham: New roles for mast cells in modulating allergic reactions and immunity against pathogens. Curr Opin Immunol 21, 679-686 (2009)
doi:10.1016/j.coi.2009.09.007
PMid:19828301 PMCid:2787974
12. H Ali: Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a. Immunology Letters 128, 36-45 (2010)
doi:10.1016/j.imlet.2009.10.007
PMid:19895849
13. NA Barrett, K. F. Austen: Innate Cells and T Helper 2 Cell Immunity in Airway Inflammation. Immunity 31, 425-437 (2009)
doi:10.1016/j.immuni.2009.08.014
PMid:19766085
14. S Maltby, K Khazaie and K. M. McNagny: Mast cells in tumor growth: Angiogenesis, tissue remodelling and immune-modulation. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1796, 19-26 (2009
15. BM Henz: Exploring the mast cell enigma: a personal reflection of what remains to be done. Exp Dermatol 17, 91-99 (2008)
doi:10.1111/j.1600-0625.2007.00658.x
PMid:18205712
16. G Pejler, E Ronnberg, I Waern, S. Wernersson: Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 115, 4981-4990 (2010)
doi:10.1182/blood-2010-01-257287
PMid:20233968
17. PJ Lindsberg, D Stribian, ML Karjalainen-Lindsberg: Mast cells as early responders in the regulation of acute blood-brain barrier changes after cerebral ischemia and hemorrhage. J Cereb Blood Flow Metab 30, 689-702 (2010)
doi:10.1038/jcbfm.2009.282
18. MC Jamur, A Moreno, L Mello, D Souza Junior, M Campos, M Pastor, A Grodzki, D Silva, C Oliver: Mast cell repopulation of the peritoneal cavity: contribution of mast cell progenitors versus bone marrow derived committed mast cell precursors. BMC Immunology 11, 32 (2010)
doi:10.1186/1471-2172-11-32
PMid:20576124 PMCid:2912243
19. L Enerbäch: Mast cells in rat gastrointerstinal mucosa 1. Effects of fixation. Acta Path et Microbiol Scandinav 66, 289 (1966)
20. L Enerbäch: Mast cells in rat gastrointestinal mucosa 2. Dye-binding and metachromatic properties. Acta Path et Microbiol Scandinav 66, 303-312 (1966)
21. L Enerbäch: Mast cells in rat gastrointestinal mucosa 3. Reactivity towards compound 48/80. Acta Path et Microbiol Scandinav 66, 313-322 (1966)
22. L Enerbäch: Mast cells in rat gastrointestinal mucosa 4. Monoamine storing capacity. Acta Path et Microbiol Scandinav 67, 365-379 (1966)
23. P Ehrlich: Beiträge zurkenntniss der granulirten bindergewebezellen und der eosinophilen leukocythen. Arch. Anat. Physiol. Physiol Abt 3, 166-169 (1879)
24. H Ginsburg, D Ben-Shahar, E Ben-David: Mast cell growth on fibroblast monolayers:two-cell entities. Immunology 45, 371-380 (1982)
PMid:7061102 PMCid:1555274
25. M Rottem, AS Dirshenbaum, DD Metcalfe: Early development of mast cells. Int Arch Allergy Appl Immunol 94, 104-109 (1991)
doi:10.1159/000235339
26. JW Combs: Maturation of mast cells. J Cell Biol 48, 676-684 (1966)
doi:10.1083/jcb.48.3.676
PMid:5545334 PMCid:2108100
27. LC Yong: The mast cell: origin, morphology, distribution, and function. Exp Toxicol Pathol 49, 409-24 (1997)
PMid:9495641
28. FM Burnet: The probable relationship of some or all mast cells to the T-cell system. Cell Immunol 30, 358-360 (1977)
doi:10.1016/0008-8749(77)90079-X
29. D Guy-Grand, C Griscelli, P. Vassalli: The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. The Journal of Experimental Medicine 148, 1661-1677 (1978)
doi:10.1084/jem.148.6.1661
PMid:31410
30. D Zucker-Franklin, G Grusky, N Hirayama, E Schnipper: The presence of mast cell precursors in rat peripheral blood. Blood 58, 544-551 (1981)
PMid:7259836
31. BM Czarnetzki, R Sonak, E Macher: Comparison of eosinophil chemotactic factor (ECF) in basophils and mast cells. Monogr Allergy 14, 281-284 (1979)
PMid:503080
32. BM Czarnetzki, W Sterry, H Bazin, KJ Kalveram: Evidence that tissue mast cells derive from mononuclear phagocytes. International Archives of Allergy and Immunology 67, 44-48 (1982)
doi:10.1159/000232986
33. W Sterry, BM Czarnetzki: In vitro differentiation of rat peritoneal macrophages into mast cells: An enzyme cytochemical study. Annals of Hematology 44, 211-220 (1982)
34. Y Kitamura, M Shimada, K Hatamaka, Y Miyano: Development of mast cells from grafted bone marrow cells in irradiated mice. Nature 268, 442-443 (1977)
doi:10.1038/268442a0
PMid:331117
35. E Chi, D Lagunoff: Abnormal mast cell granules in the beige (Chediak-Higashi syndrome) mouse. J Histochem Cytochem 23, 117-122 (1975)
PMid:46876
36. Y Kitamura, S Go, K Hatanaka: Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 52, 447-452 (1978)
PMid:352443
37. ES Russell. Hereditary anemias of the mouse: A review for geneticists. In: Advances in Genetics. Ed: EW Caspari Academic Press (1979)
PMid:390999
38. Y Kitamura, H Matsuda,K Hatanaka: Clonal nature of mast-cell clusters formed in W/Wv mice after bone marrow transplantation. Nature 281, 154-155 (1979)
doi:10.1038/281154a0
PMid:381943
39. Y Kitamura, M Shimada, S Go, H Matsuda, K Hatanaka, M. Seki: Distribution of mast-cell precursors in hematopoietic and lymphopoietic tissues of mice. J Exp Med 150, 482-490 (1979)
doi:10.1084/jem.150.3.482
PMid:383876
40. H Ginsburg: The in vitro differentiation and culture of normal mast cells from the mouse thymus. Ann N Y Acad Sci 103, 20-39 (1963)
doi:10.1111/j.1749-6632.1963.tb53690.x
41. H Ginsburg, L Sachs: Formation of pure suspensions of mast cells in tissue culture by differentiation of lymphoid cells from the mouse thymus. J Natl Cancer Inst 28, 1-39 (1963)
42. T Ishizaka, T Adachi, T-H Chang, K Ishizaka: development of mast cells in vitro: II. Biologic function of cultured mast cells. J Immunol 118, 211-217 (1977)
PMid:63515
43. T Ishizaka, H Okudaira, LE Mauser, K Ishizaka: Development of rat mast cells in vitro: I. differentiation of mast cells from thymus cells. J Immunol 116, 747-754 (1976)
PMid:1254953
44. H Ginsburg, D Lagunoff: The in vitro differentiation of mast cells. Cultures of cells from immunized mouse lymph nodes and thoracic duct lymph on fibroblast monolayers. J Cell Biol 35, 685-697 (1967)
doi:10.1083/jcb.35.3.685
PMid:4863559 PMCid:2107161
45. H Ginsburg: Differntiation and activity of mast cells followin immunization in cultures of lymph-node cells. Immunology 35, 485-502 (1978)
PMid:700779 PMCid:1457637
46. G Mayrhofer, R Fisher: Mast cells in severely T-cell depleted rats and the response to infestation with Nippostrongylus brasiliensis. Immunology 37, 145-155 (1979)
PMid:313898 PMCid:1457312
47. Y Kitamura, S Go, K Hatanaka: Decrease of mast cell in W/Wv mice and their increase by bone marrow transplantation. Blood 52, 447-452 (1978)
PMid:352443
48. G Nabel, SJ Galli, AM Dvorak, H Dvorak, H Cantor: Inducer T lymphocytes synthesize a factor that stimulate proliferation of cloned mast cells. Nature 291, 332-334 (1981)
doi:10.1038/291332a0
PMid:6972009
49. K Nagao, K Yokoro, S Aaronsaon: Continuous lines of basophil/mast cells derived from normal mouse bone marrow. Science 212, 333-335 (1981)
doi:10.1126/science.7209531
PMid:7209531
50. E Razin, C Cordon-Cardo, RA Good: Growth of a pure population of mouse mast cells in vitro with conditioned medium derived from concanavalin A-stimulated splenocytes. PNAS (USA) 78, 2559-2561 (1981)
doi:10.1073/pnas.78.4.2559
PMid:6969751
52. G Tertian, Y Yung, D Guy-Grand, M Moore: Long-term in vitro culture of murine mast cells. I. Description of a growth factor-dependent culture technique. J Immunol 127, 788-794 (1981)
PMid:7019332
53. S Hasthorpe: A hemopoietic cell line dependent upon a factor in pokeweed mitogen-stimulated spleen cell conditioning medium. J Cell Physiol 105, 379-384 (1980)
doi:10.1002/jcp.1041050221
PMid:7462332
54. B Sredni, M Friedman, C Bland, D Metcalfe: Ultrastructural, biochemical, and functional characteristics of histamine-containing cells cloned from mouse bone marrow: tentative identification as mucosal mast cells. J Immunol 131, 915-922 (1983)
PMid:6575098
55. Y Yung, R Eger, G Tertian, M Moore: Long-term in vitro culture of murine mast cells. II. Purification of a mast cell growth factor and its dissociation from TCGF. J Immunol 127, 794-799 (1981)
PMid:6788848
56. Y Yung, M Moore: Long-term in vitro culture of murine mast cells. III. Discrimination of mast cells growth factor and granulocyte-CSF. J Immunol 129, 1256-1261 (1982)
PMid:6809816
57. J Ihle, L Pepersack, L Rebar: Regulation of T cell differentiation: in vitro induction of 20 alpha- hydroxysteroid dehydrogenase in splenic lymphocytes from athymic mice by a unique lymphokine. J Immunol 126, 2184-2189 (1981)
PMid:6971890
58. J Lee, A Hapel, J Ihle: Constitutive production of a unique lymphokine (IL 3) by the WEHI-3 cell line. J Immunol, 128, 2393-2398 (1982)
PMid:6122701
59. J Ihle, J Keller, L Henderson, F Klein, E Palaszynski: Procedures for the purification of interleukin 3 to homogeneity. J Immunol 129, 2431-2436 (1982)
PMid:6815268
60. J Ihle, J Keller, S Oroszlan, L Henderson, T Copeland, F Fitch, M Prystowsky, E Goldwasser, J Schrader, E Palaszynski, M Dy, B Lebel: Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell- stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. J Immunol 131, 282-287 (1983)
PMid:6190911
61. MC Fung, A J Hapel, S Ymer, DR Cohen, AR Johnson, HD Campbell, RM Young: Molecular cloning of cDNA for murine interleukin-3. Nature 307, 233-237 (1984)
doi:10.1038/307233a0
PMid:6420702
62. D Metcalf: The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood 67, 257-267 (1986)
PMid:3002522
63. M Prystowsky, G Otten, M Naujokas, J Vardiman, J Ihle, E Goldwasser, F Fitch: Multiple hemopoietic lineages are found after stimulation of mouse bone marrow precursor cells with interleukin 3. Am J Pathol 117, 171-179 (1984)
PMid:6437231 PMCid:1900437
64. E Razin, J Ihle, D Seldin, J Mencia-Huerta, H Katz, P LeBlanc, A Hein, J Caulfield, K Austen, R. Stevens: Interleukin 3: A differentiation and growth factor for the mouse mast cell that contains chondroitin sulfate E proteoglycan. J Immunol,132, 1479-1486 (1984)
PMid:6198393
65. Y Hamaguchi, Y Kanakura, J Fujita, S Takeda, T Nakano, S Tarui, T Honjo, Y Kitamura: Interleukin 4 as an essential factor for in vitro clonal growth of murine connective tissue-type mast cells. The Journal of Experimental Medicine 165, 268-273 (1987)
doi:10.1084/jem.165.1.268
PMid:3491870
66. T Nakahata, T Kobyashi, A Ishiguro: Extensive proliferation of mature connective tissue type mast cells in vitro. Nature 324, 65-67 (1986)
doi:10.1038/324065a0
PMid:3491321
67. SJ Galli, M Tsai, BK Wershil: The c-kit receptor, stem cell factor and mast cells. What each is teaching us about the others. Am J Pathology 142, 965-974 (1993)
PMid:7682764 PMCid:1886888
68. DM Anderson, SD Lyman, A Baird, JM Wignall, J Eisenman, C Rauch, C J March, HS Boswell, SD Gimpel, D Cosman, DE Williams: Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell 63, 235-243 (1990)
PMid:1699134
69. NG. Copeland, DJ Gilbert, BC Cho, PJ Donovan, N A Jenkins, DCosman, DAnderson, SD Lyman, DE Williams: Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell 63, 175-183 (1990)
PMid:1281684
70. JG Flanagan, P Leder: The kit ligand: A cell surface molecule altered in steel mutant fibroblasts. Cell 63, 185-194 (1990)
71. E Huang, K Nocka, DR Beier, T-Y Chu, J Buck, H-W Lahm, D Wellner, P Leder, P Besmer: The hematopoietic growth factor KL is encoded by the SI locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 63, 225-233 (1990)
PMid:1698611 PMCid:552065
72. FH Martin, SV Suggs, KE Langley, HS Lu, J Ting, KH Okino, CF Morris, I K McNiece, FW Jacobsen, EA Mendlaz, NC Birkett, KA Smith, MJ Johnson, VP Parker, JC Flores, AC Patel, EF Fisher, HO Erjavec, CJ Herrera, J Wypych, RK Sachdev, JA Pope, I Leslie, D Wen, C-H Lin, RL Cupples, KM Zsebo: Primary structure and functional expression of rat and human stem cell factor DNAs. Cell 63, 203-211 (1990)
PMid:7508684 PMCid:1887147
73. H Matsui, KM Zsebo, BLM Hogan: Embryonic expression of a hematopoietic growth factor encoded by the Sl locus and the ligand for c-kit. Nature 347, 667-669 (1990)
doi:10.1038/347667a0
PMid:7678600 PMCid:330008
74. DE Williams, J Eisenman, A Baird, C Rauch, K Van Ness, CJ March, LS Park, U Martin, DY Mochizukl, HSBoswell, GS Burgess, D Cosman, SD Lyman: Identification of a ligand for the c-kit proto-oncogene. Cell 63, 167-174 (1990)
75. KM Zsebo, DA Williams, EN. Geissler, VC Broudy, FH Martin, HL Atkins, R-Y Hsu, NC Birkett, KH Okino, DC Murdock, FW Jacobsen, KE Langley, KA Smith, T Takeish, BM Cattanach, SJ Galli, SV Suggs: Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 63, 213-224 (1990)
PMid:3259238
76. KM Zsebo, J Wypych, IK. McNiece, HS Lu, KA Smith, SB Karkare, RK Sachdev, VN Yuschenkoff, NC Birkett, LR Williams, VN Satyagal, W Tung, RA Bosselman, EA Mendiaz, KE Langley: Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver-conditioned medium. Cell 63, 195-201 (1990)
PMid:2138633 PMCid:296556
77. AA Irani, G Nilsson, U Miettinen, S Craig, L Ashman, T Ishizaka, K Zsebo, L Schwartz: Recombinant human stem cell factor stimulates differentiation of mast cells from dispersed human fetal liver cells. Blood 80, 3009-3021 (1992)
PMid:1372640
78. AA Irani, S Craig, G Nilsson, T Ishizaka, LB Schwartz: Characterization of human mast cells developed in vitro from fetal liver cells cocultured with murine 3T3 fibroblasts. Immunol 77, 136-143 (1992)
PMid:8376776
79. K Nocka, J Buck, J Levi, P Besmer: Candidate ligand for the c-kit trans-membrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. EMBO J 9, 3287-3294 (1990)
80. A Iemura, M Tsai, A Ando, BK Wershil, SJ Galli: The c-kit ligand, stem cell factor, promotes mast cell survival by supressing apoptosis. Am. J. Pathol 144, 321-328 (1994)
81. SJ Galli, A Iemura, DS Garlick, C Gamba-Vitalo, KM Zsebo, RG Andrews: Reversible expansion of primate mast cell populations in vivo by stem cell factor. J Clin Invest 91, 148-152 (1993)
doi:10.1172/JCI116164
PMid:8629001
82. YP Yung, MAS Moore, Mast-cell growth factor:Its role in mast cell differentiation, proliferation, and maturation. In: Contemporary Topics in Molecular Immunology Eds: RP Inmann, S Gillis. Plenum Press (1984)
PMid:15718418
83. JG Bender, DE Van Epps and CC Stewart: Characterization of granulocytes and mast cells in cultures of mouse bone marrow stimulated with interleukin-3. J Cellular Physiol 135, 71-78 (1988)
doi:10.1002/jcp.1041350110
PMid:18295888
84. HL Thompson, DD Metcalfe, J.-P. Kinet: Early expression of high-affinity receptor for immunoglobulin E (Fc epsilon RI) during differentiation of mouse mast cells and human basophils. J Clin Invest 85, 1227-1233 (1990)
doi:10.1172/JCI114557
PMid:16006518 PMCid:1183570
85. MF Gurish, N Ghildyal, HP McNeil, KF Austen, S Gillis, RL Stevens: Differential expression of secretory granule proteases in mouse mast cells exposed to interleukin 3 and c-kit ligand. J Exp Med, 175, 1003-1012 (1992)
doi:10.1084/jem.175.4.1003
PMid:10498605
86. N Ghildyal, D Friend, C Nicodemus, K Austen, R Stevens: Reversible expression of mouse mast cell protease 2 mRNA and protein in cultured mast cells exposed to IL-10. J Immunol 151, 3206-3214 (1993)
87. TR Mosmann, MW Bond, RL Coffman, J Ohara, WE Paul: T-cell and mast cell lines respond to B-cell stimulatory factor 1. PNAS (USA) 83(15), 5654-5658 (1986)
doi:10.1073/pnas.83.15.5654
PMid:2647850
88. CA Smith, DM Rennick: Characterization of a murine lymphokine distinct from interleukin 2 and interleukin 3 (IL-3) possessing a T-cell growth factor activity and a mast-cell growth factor activity that synergizes with IL-3. PNAS(USA) 83(6), 1857-1861 (1986)
doi:10.1073/pnas.83.6.1857
89. H-R Rodewald, M Dessing, AM Dvorak, SJ Galli: Identification of a committed precursor for the mast cell lineage. Science 271, 818-822 (1996)
doi:10.1126/science.271.5250.818
PMid:1704394
90. MC Jamur, ACG Grodzki, E Berestein, MM Hamaway, RP Siraganian, C Oliver: Identification and characterization of undifferentiated mast cells in mouse bone marrow. Blood 105, 4282-4289 (2005)
doi:10.1182/blood-2004-02-0756
PMid:8805662
91. MF Guiraldelli, EH Berenstein, ACG Grodzki, RP Siraganian, MC Jamur, C Oliver: The low affinity IgG receptor Fc(gamma)RIIB contributes to the binding of the mast cell specific antibody, mAb BGD6. Molecular Immunology 45, 2411-2418 (2008)
doi:10.1016/j.molimm.2007.07.041
PMid:7688344 PMCid:1421867
92. C-C Chen, MA Grimbaldeston, M Tsai, IL Weissman, SJ Galli: Identification of mast cell progenitors in adult mice. PNAS(USA) 102, 11408-11413 (2005)
doi:10.1073/pnas.0504197102
PMid:1692538
93. AS Kirshenbaum, JP Goff, T Semere, B Foster, LM Scott, DD Metcalfe: Demonstration that human mast cells arise from a progenitor cell population that is CD34+, c-kit+, and expresses aminopeptidase N (CD13). Blood 94, 2333-2342 (1999)
PMid:1698558
94. H Saito, K Hatake, AM Dvorak, KM Leiferman, AD Donnenberg, N Arai, K Ishizaka, T Ishizaka: Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins. PNAS(USA) 85(7), 2288-2292 (1988)
doi:10.1073/pnas.85.7.2288
PMid:1698554
95. A Kirshenbaum, J Goff, S Dreskin, A Irani, L Schwartz and D Metcalfe: IL-3-dependent growth of basophil-like cells and mastlike cells from human bone marrow. J Immunol 142, 2424-2429 (1989)
PMid:1698555
96. AS Kirshenbaum, JP Goff and DD Metcalfe: Human macrophages cultured on agar but not agarose resemble mast cells. Immunol 68, 120-125 (1989)
PMid:1698557
97. AS Kirshenbaum, SW Kessler, JPGoff, DD Metcalfe: Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells. J. Immunol 146(5), 1410-1414 (1991)
PMid:2208279
98. H Chen, C Kinzer, W Paul: p161, a murine membrane protein expressed on mast cells and some macrophages, is mouse CD13/aminopeptidase N. J Immunol 157, 2593-2600 (1996)
PMid:1698553
99. G Nilsson, K Forsberg, MP Bodger, LK Ashman, KM Zsebo, T Ishizaka, AM Irani, LB Schwartz: Phenotypic characterization of stem cell factor-dependent human fowetal liver-derived mast cells. Immunology 79, 325-330 (1993)
PMid:1698556
100. CI Civin: Human monomyeloid cell membrane antigens. Exp Hematol 18, 461-467 (1990)
PMid:2208278
102. M Castells: Update on mast cells and mast cell precursors and hypersensitivity responses. Allergy and Asthma Proc 18, 287-292 (1997)
doi:10.2500/108854197778590506
PMid:9337422
103. M Castells: Mast cells:Molecular and cell biology. Internet J Asthma Allergy Immunol 1 (1999)
104. DW Fawcett: An experimental study of mast cell degranulation and regeneration. Anat Rec 121, 29-43 (1955)
doi:10.1002/ar.1091210104
PMid:14350265
105. MC Jamur, I Vugman, AR Hand: Ultrastructural and cytochemical studies of acid phosphatase and trimetaphosphatase in rat peritoneal mast cells developing in vivo. Cell Tissue Res, 244, 557-563 (1986)
doi:10.1007/BF00212533
106. VO Mendonca, I Vugman, MC Jamur: Maturation of adult rat peritoneal and mesenteric mast cells. A morphological and histofluorescence study. Cell Tissue Res 243, 635-639 (1986)
doi:10.1007/BF00218072
107. LC Yong, SG Watkins, JE Boland: The mast cell: III. Distribution and maturation in various organs of the young rat. Pathology 11, 427-45 (1979)
doi:10.3109/00313027909059020
PMid:523184
108. LC Yong: The mast cell: IV. An ultrastructural and autoradiographic study of the distribution and maturation of peritoneal mast cells in the rat. Pathology 13, 497-515 (1981)
doi:10.3109/00313028109059067
PMid:7197771
109. CD Faraco, I Vugman, RP Siraganian, MC Jamur, C Oliver: Immunocytochemical identification of immature rat peritoneal mast cells using a monoclonal antibody specific for rat mast cells. Acta Histochem 99, 23-27 (1997)
PMid:9150793
110. XJ Chen, L Enerback: Application of an immunocolloid gold technique for the ultrastructural demonstration of IgE-receptor complexes on rat mast cells. APMIS 102, 729-735 (1994)
doi:10.1111/j.1699-0463.1994.tb05227.x
PMid:7826601
111. RI Ashman, DL Jarboe, DH Conrad, TF Huff: The mast cell-committed progenitor: In vitro generation of committed progenitors from bone marrow. J Immunol 146, 211-216 (1991)
PMid:1898599
112. TF Huff, CS Lantz, J Ryan, JA Leftwich: Mast cell-committed progenitors. In: Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function. Eds Y Kitamura, Y Yamamoto, SJ Galli, MW Greaves. Raven Press (1995)
113. HL Thompson, PD Burnbelo, DD Metcalfe: Regulation of adhesion of mouse bone marrow-derived mast cells to laminin. J. Immunology 145, 3425-3431 (1990)
PMid:2146320
114. C Lantz, TF Huff: Murine KIT+ lineage bone marrow progenitors express FceRII, but do not express FCeRI until mast cell granule formation. J Immunol 154, 355 (1995)
PMid:7527815
115. MC Jamur, AC Grodzki, AN Moreno, LFC Mello, VP Davila, RP Siraganian, C Oliver: Identification and isolation of rat bone marrow-derived mast cells using the mast cell-specific monoclonal antibody AA4. J Histochem Cytochem 49, 219-228 (2001)
PMid:11156690
116. DF Bainton, MG Farquhar: Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. J Cell Biol 39, 299-317 (1968)
doi:10.1083/jcb.39.2.299
PMid:5692583 PMCid:2107532
117. DF Bainton, MG Farquhar: Segregation and packaging of granule enzymes in eosinophilic leukocytes. J Cell Biol 45, 54-73 (1970)
doi:10.1083/jcb.45.1.54
PMid:5459000 PMCid:2108001
118. BA Nichols, DF Bainton: Differentiation of human monocytes in bone marrow and blood. Sequential formation of two granule populations. Lab. Invest., 29, 27-40 (1973)
PMid:4728355
119. BA Nichols, DF Bainton, MGFarquhar: Differentiation of monocytes. J Cell Biol 50, 498-515 (1971)
doi:10.1083/jcb.50.2.498
PMid:4107019 PMCid:2108281
120. KF Austen, JA Boyce: Mast cell lineage development and phenotypic regulation. Leuk Res 25, 511-518 (2001)
doi:10.1016/S0145-2126(01)00030-3
121. SJ Galli, J Kalesnikoff, MA Grimbaldeston, AM Piliponsky, CMM Williams, M Tsai: Mast cells as "tunable" effector and immunoregulatory cells: Recent advances. Annu Rev Immunol 23, 749-786 (2005)
doi:10.1146/annurev.immunol.21.120601.141025
PMid:15771585
122. C Godfraind, J Louahed, H Faulkner, A Vink, G Warnier, R Grencis, J-C Renauld: Intraepithelial Infiltration by mast cells with both connective tissue-type and mucosal-type characteristics in gut, trachea, and kidneys of IL-9 transgenic mice. J Immunol 160, 3989-3996 (1998)
PMid:9558107
123. E Crivellato, CA Beltrami, F Mallardi, D Ribatti: The mast cell: an active participant or an innocent bystander? Histol Histopathol 19, 259-270 (2004)
PMid:14702194
124. Z-Q Hu, W-H Zhao and T Shimamura: Regulation of mast cell development by inflammatory factors. Curr Med Chem 14, 3044-3050 (2007)
doi:10.2174/092986707782793998
PMid:18220740
125. O Kassel, C da Silv, N Frossard: The Stem Cell Factor, its Properties and Potential Role in the Airways. Pulmonary Pharmacol Therapeut 14, 277-288 (2001)
doi:10.1006/pupt.2001.0304
126. B Chabot, DA Stephenson, VM Chapman, P Besmer, A Bernstein: The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 335, 88-89 (1988)
doi:10.1038/335088a0
PMid:2457811
127. Y Kitamura, S Go: Decreased production of mast cells in S1/S1d anemic mice. Blood 53, 492-497 (1979)
PMid:367470
128. K Tsuji, T Nakahata, M Takagi, T Kobayashi, A Ishiguro, T Kikuchi, K Naganuma, K Koike, A Miyajima, K Arai: Effects of interleukin-3 and interleukin-4 on the development of "connective tissue-type" mast cells: interleukin-3 supports their survival and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3. Blood 75, 421-427 (1990)
PMid:2295001
129. D Rennick, B Hunte, G Holland, L Thompson-Snipes: Cofactors are essential for stem cell factor-dependent growth and maturation of mast cell progenitors: comparative effects of interleukin-3 (IL-3), IL-4, IL-10, and fibroblasts. Blood 85, 57-65 (1995)
PMid:7528573
130. Y Mekori, C Oh, D Metcalfe: IL-3-dependent murine mast cells undergo apoptosis on removal of IL-3. Prevention of apoptosis by c-kit ligand. J Immunol 151(7), 3775-3784 (1993)
PMid:7690814
131. M Yanagida, H Fukamachi, K Ohgami, T Kuwaki, H Ishii, H Uzumaki, K Amano, T Tokiwa, H Mitsui, H Saito: Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and IL-6 on the survival of cultured human mast cells. Blood 86(10), 3705-3714 (1995)
PMid:7579337
132. H Ochi, W M Hirani, Q Yuan, DS Friend, KF Austen, JA Boyce: T Helper Cell Type 2 Cytokine-Mediated Comitogenic Responses and Ccr3 Expression during Differentiation of Human Mast Cells in vitro. J Exp Med 190, 267-280 (1999)
doi:10.1084/jem.190.2.267
PMid:10432289 PMCid:2195573
133. K Karimi, FA Redegeld, B Heijdra, FP Nijkamp: Stem cell factor and Interleukin-4 induce murine bone marrow cells to develop into mast cells with connective tissue type characteristics in vitro. Exp Hematol 27(4), 654-662 (1999)
doi:10.1016/S0301-472X(98)00083-6
134. CF Yeatman, SM Jacobs-Helber, P Mirmonsef, SR Gillespie, LA Bouton, H A Collins, ST Sawyer, CP Shelburne and JJ Ryan: Combined Stimulation with the T Helper Cell Type 2 Cytokines Interleukin (Il)-4 and IL-10 Induces Mouse Mast Cell Apoptosis. J Exp Med 192, 1093-1104 (2000)
doi:10.1084/jem.192.8.1093
PMid:11034599 PMCid:2195863
135. A Lorentz, S Bischoff: Regulation of human intestinal mast cells by stem cell factor and IL-4. Immunol Rev, 179, 57-60 (2001)
doi:10.1034/j.1600-065X.2001.790106.x
PMid:11292028
136. H Xia, Z Du, S Craig, G Klisch, N Noben-Trauth, J Kochan, T Huff, A Irani, L Schwartz: Effect of recombinant human IL-4 on tryptase, chymase, and Fc epsilon receptor type I expression in recombinant human stem cell factor- dependent fetal liver-derived human mast cells. J Immunol 159, 2911-2921 (1997)
PMid:9300715
137. Z-Q Hu, K Kobayashi, N Zenda, T Shimamura: Tumor Necrosis Factor-alpha and Interleukin-6-Triggered Mast Cell Development From Mouse Spleen Cells. Bloo, 89, 526-533 (1997)
138. Q Yuan, MF Gurish, DS Friend, KF Austen, JA Boyce: Generation of a Novel Stem Cell Factor-Dependent Mast Cell Progenitor. J Immunol 161, 5143-5146 (1998)
PMid:9820483
139. G Nilsson, U Miettinen, T Ishizaka, L Ashman, A Irani, L Schwartz: Interleukin-4 inhibits the expression of Kit and tryptase during stem cell factor-dependent development of human mast cells from fetal liver cells. Blood 84, 1519-1527 (1994)
PMid:7520776
140. C Sillaber, WR Sperr, H Agis, E Spanblöchl, K Lechner, P. Valent: Inhibition of Stem Cell Factor Dependent Formation of Human Mast Cells by lnterleukin-3 and lnterleukin-4. Internat Archives Allergy and Immunol 105, 264-268 (1994)
doi:10.1159/000236767
PMid:7522690
141. CA Oskeritzian, Z Wang, JP Kochan, M Grimes, Z Du, H-W Chang, S Grant, LB Schwartz: Recombinant Human (rh)IL-4-Mediated Apoptosis and Recombinant Human IL-6-Mediated Protection of Recombinant Human Stem Cell Factor-Dependent Human Mast Cells Derived from Cord Blood Mononuclear Cell Progenitors. J Immunol 163, 5105-5115 (1999)
PMid:10528217
142. T Nakahata, H Toru: Cytokines Regulate Development of Human Mast Cells from Hematopoietic Progenitors. Internatl J Hematol 75, 350-356 (2002)
doi:10.1007/BF02982123
PMid:12041663
143. E Gyotoku, E Morita, Y Kameyoshi, T Hiragun, S Yamamoto, M Hide: The IL-6 family cytokines, interleukin-6, interleukin-11, oncostatin M, and leukemia inhibitory factor, enchance mast cell growth through fibroblast-dependent pathway in mice. Ach Dermatol Res 293, 508-514 (2001)
doi:10.1007/PL00007465
PMid:11820727
144. H Saito, M Ebisawa, H Tachimoto, M Shichijo, K Fukagawa K Matsumoto, Y Iikura, T Awaji, G Tsujimoto, M Yanagida, H Uzumaki, G Takahashi, K Tsuji, T Nakahata: Selective growth of human mast cells induced by Steel factor, IL-6, and prostaglandin E2 from cord blood mononuclear cells. J Immunol 157, 343-350 (1996)
PMid:8683136
145. S J Galli: Biology of disease. New insigts into "the riddle of the mast cells". Microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab. Invest. 62, 5-33 (1990)
PMid:2404155
146. T Kinoshita, N Sawai, E Hidaka, T Yamashita, K Koike: Interleukin-6 Directly Modulates Stem Cell Factor-Dependent Development of Human Mast Cells Derived From CD34+ Cord Blood Cells. Blood 94, 496-508 (1999)
PMid:10397717
147. L Hültner, C Druez, JMoeller, C. Uyttenhove, E Schmitt, E Rüde, P. Dörmer, J. van Snick: Mast cell growth-enhancing activity (MEA) is structurally related and functionally identical to the novel mouse T cell growth factor P40/TCGFIII (interleukin 9). Europ J Immunol 20, 1413-1416 (1990)
148. S Matsuzawa, K Sakashita, T Kinoshita, S Ito, T Yamashita,K. Koike: IL-9 Enhances the Growth of Human Mast Cell Progenitors Under Stimulation with Stem Cell Factor. J Immunol 170, 3461-3467 (2003)
PMid:12646606
149. L Thompson-Snipes, V Dahr, MW Bond, TR Mosmann, KW Moore, DM Rennick: Interleukin 10: a novel stimulatiory factor for mast cells and their progenitors. J Exp Med 173, 507-510 (1991)
doi:10.1084/jem.173.2.507
PMid:1899106
150. SK Norton, B Barnstein, J Brenzovich, DP Bailey, M Kashyap, K Speiran, J Ford, D Conrad, S Watowich, MR Moralle, C L Kepley, PJ Murray, JJ Ryan: IL-10 Suppresses Mast Cell IgE Receptor Expression and Signaling In vitro and In vivo. J Immunol 180, 2848-2854 (2008)
doi:10.1172/JCI118506
PMid:8613537 PMCid:507161
152. SR Gillespie, RR DeMartino, J Zhu, HJ Chong, C Ramirez, CP Shelburne, LA Bouton, DP Bailey, A Gharse, P Mirmonsef, S Odom, G Gomez, J Rivera, K Fischer-Stenger, JJ Ryan: IL-10 Inhibits Fc{epsilon}RI Expression in Mouse Mast Cells. J Immunol 172, 3181-3188 (2004)
PMid:14978125
153. DP Bailey, M Kashyap, LA Bouton, PJ Murra, JJ Ryan: Interleukin-10 induces apoptosis in developing mast cells and macrophages. J Leukoc Biol 80, 581-589 (2006)
doi:10.1189/jlb.0405201
PMid:16829633
154. D Kaur, F Hollins, L Woodman, W Yang, P Monk, R May, P Bradding, CE Brightling: Mast cells express IL-13Rα1: IL-13 promotes human lung mast cell proliferation and FcɛRI expression. Allergy 61, 1047-1053 (2006)
doi:10.1111/j.1398-9995.2006.01139.x
PMid:16918506
155. A Masuda, T Matsuguchi, K Yamaki, T Hayakawa, M Kubo, WJ LaRochelle, Y Yoshikai: Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of Interleukin-4 in mouse mast cells. J Biol Chem 275, 29331-29337 (2000)
doi:10.1074/jbc.M910290199
PMid:10882748
156. A Masuda, T Matsuguchi, K Yamaki, T Hayakawa, Y Yoshikai: Interleukin-15 prevents mouse mast cell apoptosis through STAT6-mediated Bcl-xL expression. J Biol Chem 276, 26107-26113 (2001)
doi:10.1074/jbc.M011475200
PMid:11369758
157. JC Qi, RL Stevens, R Wadley, A Collins, M Cooley, HM Naif, N Nasr, A Cunningham, G Katsoulotos, Y Wanigasek, B Roufogalis, SA Krilis: IL-16 regulation of human mast cells/basophils and their susceptibility to HIV-1. J Immunol 168, 4127-4134 (2002)
PMid:11937573
158. K Horigome, ED Bullock, EM Johnson: Effects of nerve growth factor on rat peritoneal mast cells. Survival promotion and immediate-early gene induction. J Biol Chem 269, 2695-2702 (1994)
PMid:8300599
159. ED Bullock, EM Johnson: Nerve growth factor induces the expression of certain cytokine genes and bcl-2 in mast cells. J Biol Chem 271, 27500-27508 (1996)
doi:10.1074/jbc.271.44.27500
PMid:8910334
160. A Richard, SR McCol, G. Pelletier: Interleukin-4 and nerve growth factor can act as cofactors for interleukin-3-induced histamine production in human umbilical cord blood cells in serum-free culture. British J of Haematol 81, 6-11 (1992)
doi:10.1111/j.1365-2141.1992.tb08162.x
PMid:1520626
161. P Welker, J Grabbe, A Grützkau, BM Henz: Effects of nerve growth factor (NGF) and other firbrblast-derived growth factors on immature human mast cells (HMC-1). Immunology 94, 310-317 (1998)
PMid:9771435 PMCid:1364247
162. H Matsuda, Y Kannan, H Ushio: Nerve growth factor induces development of connective tissue-type mast cells in vitro from murine bone marrow cells. J Exp. Med 174, 7-14 (1991)
doi:10.1084/jem.174.1.7
PMid:1711569
163. K Kawamoto, T Okada, Y Kannan, H Ushio, M Matsumoto, H Matsuda: Nerve growth factor prevents apoptosis of rat peritoneal mast cells through the trk proto-oncogene receptor. Blood 86, 4638-4644 (1995)
PMid:8541555
164. N Kanbe, M Kurosawa, Y Miyachi, M Kanbe, H Saitoh, H Matsuda: Nerve growth factor prevents apoptosis of cord blood-derived human cultured mast cells synergistically with stem cell factor. Clin Exp Allergy 30, 1113-1120 (2000)
doi:10.1046/j.1365-2222.2000.00866.x
165. HV Wright, D Bailey, M Kashyap, CL Kepley, MS Drutskaya, SA Nedospasov, JJ Ryan: IL-3-mediated TNF production is necessary for mast cell development. J Immunol 176, 2114-2121 (2006)
PMid:16455967
166. FNorozian, M. Kashyap, CD Ramirez, N Patel, CL Kepley, BO Barnstein, JJ Ryan: TGF(beta)1 induces mast cell apoptosis. Exp Hematol 34, 579-587 (2006)
PMid:16647563
167. T Gebhardt, A Lorentz, F Detmer, C Trautwein, H Bektas, MP Manns, SC Bischoff: Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor β1. Gut 54, 928-934 (2005)
PMid:18981148 PMCid:2645416
68. W Zhao, G Gomez, S-H Yu, JJ Ryan, LB Schwartz: TGF-{beta}1 attenuates mediator release and de novo kit expression by human skin mast cells through a smad-dependent pathway. J Immunol 181, 7263-7272 (2008)
PMid:2527268
169. D Broide, S Wasserman, J Alvaro-Gracia, N Zvaifler, G Firestein: Transforming growth factor-beta 1 selectively inhibits IL-3-dependent mast cell proliferation without affecting mast cell function or differentiation. J Immunol 143, 1591-1597 (1989)
PMid:16263412
170. M Kashyap, DP Bailey, G Gomez, J Rivera, TF Huff, JJ Ryan: TGF-(beta)1 inhibits late-stage mast cell maturation. Exp Hematol 33(11), 1281-1291 (2005)
doi:10.1016/j.exphem.2005.07.001
PMid:7519644
171. Y Mekori, D Metcalfe: Transforming growth factor-beta prevents stem cell factor-mediated rescue of mast cells from apoptosis after IL-3 deprivation. J Immunol 153, 2194-2203 (1994)
PMid:7514900
172. C Dubois, F Ruscetti, J Stankova, J. Keller: Transforming growth factor-beta regulates c-kit message stability and cell-surface protein expression in hematopoietic progenitors. Blood, 83, 3138-3145 (1994)
PMid:7539249
173. N Toyota, Y Hashimoto, S Matsuo, H Iizuka: Transforming growth factor beta 1 inhibits IL-3- and IL-4-dependent mouse connective tissue-type mast cell proliferation. Arch Dermatol Re, 287, 198-201 (1995)
doi:10.1007/BF01262332
PMid:16839529
174. M Funaba, K Nakaya, T Ikeda, M Murakami, K Tsuchida, H. Sugino: Requirement of Smad3 for mast cell growth. Cell Immunol 240, 47-52 (2006)
doi:10.1016/j.cellimm.2006.06.002
PMid:10233900
175. HRP Miller, SH Wright, PA Knight, EM Thornton: A novel function for transforming growth factor-{beta}1: upregulation of the expression and the IgE-independent extracellular release of a mucosal mast cell granule-specific {beta}-chymase, mouse mast cell protease-1. Blood 93, 3473-3486 (1999)
176. SH Wright, J Brown, PA Knight, EM Thornton, PJ Kilshaw, HRP Miller: Transforming growth factor-bβ1 mediates coexpression of the integrin subunit aαE and the chymase mouse mast cell protease-1 during the early differentiation of bone marrow-derived mucosal mast cell homologues. Clin Exp Allergy 32, 315-324 (2002)
doi:10.1046/j.1365-2222.2002.01233.x
177. M Funaba, T Ikeda, M Murakami, K Ogawa, Y Nishino, K Tsuchida, H Sugino, M Abe: Transcriptional regulation of mouse mast cell protease-7 by TGF-(beta). Biochim Biophys Acta (BBA) - Gene Structure and Expression, 1759, 166-170 (2006)
PMid:15451032
178. M Funaba, T Ikeda, M Murakami, K Ogawa, M. Abe: Up-regulation of mouse mast cell protease-6 gene by transforming growth factor-(beta) and activin in mast cell progenitors. Cell Signalling 17, 121-128 (2005)
doi:10.1016/j.cellsig.2004.06.005
PMid:12773512
179. M Funaba, T Ikeda, K Ogawa, M Murakami, M Abe: Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration. J Leukoc Biol 73, 793-801 (2003)
doi:10.1189/jlb.0103012
PMid:10339477
180. N. Sawai, K. Koike, H. H. Mwamtemi, T. Kinoshita, Y. Kurokawa, K. Sakashita, T. Higuchi, K. Takeuchi, M. Shiohara, T. Kamijo, S. Ito, T. Kato, H. Miyazaki, T. Yamashita and A. Komiyama: Thrombopoietin Augments Stem Cell Factor-Dependent Growth of Human Mast Cells From Bone Marrow Multipotential Hematopoietic Progenitors. Blood 93(11), 3703-3712 (1999)
PMid:15781331
181. AS Kirshenbaum, C Akin, JP Goff, DD Metcalfe: Thrombopoietin alone or in the presence of stem cell factor supports the growth of KIT(CD117)low/ MPL(CD110)+ human mast cells from hematopoietic progenitor cells. Exp Hematol 33, 413-421 (2005)
doi:10.1016/j.exphem.2004.12.005
PMid:18276801 PMCid:2741730
182. F Martelli, B Ghinassi, R Lorenzini, AM Vannucchi, RA Rana, M Nishikawa, S Partamian, G Migliaccio, AR Migliaccio: Thrombopoietin inhibits murine mast cell differentiation. Stem Cells 26(4), 912-919 (2008)
doi:10.1634/stemcells.2007-0777
PMid:17468237
183. AR Migliaccio, RA Rana, AM Vannucchi, FA Manzoli: role of thrombopoietin in mast cell differentiation. Ann NY Acad Sci 1106, 152-174 (2007)
doi:10.1196/annals.1392.024
PMid:19025339
184. B Ghinassi, M Zingariello, F Martelli, R Lorenzini, AM Vannucchi, RA Rana, M Nishikawa, G Migliaccio, J Mascarenhas, A R Migliaccio: Increased differentiation of dermal mast cells in mice lacking the Mpl gene. Stem Cells Develop 18, 1081-1092 (2009)
doi:10.1089/scd.2008.0323
PMid:9502621
185. AS Kirshenbaum, AS Worobec, TA Davis, JP Goff, T Semere, DD Metcalf: Inhibition of human mast cell growth and differentiation by interferon gamma-1b. Exp Hematol 26, 245-251 (1998)
PMid:2118156
186. M Takagi, K Koike, T Nakahata: Antiproliferative effect of IFN-gamma on proliferation of mouse connective tissue-type mast cells. J Immunol 145, 1880-1884 (1990)
PMid:2471732
187. R Bressler, H Thompson, J Keffer, D Metcalfe: Inhibition of the growth of IL-3-dependent mast cells from murine bone marrow by recombinant granulocyte macrophage-colony-stimulating factor. J Immunol 143, 135-139 (1989)
PMid:10779427
188. T Kinoshita, K Koike, HH Mwamtemi, S Ito, S Ishida, Y Nakazawa, Y Kurokawa, K Sakashita, T Higuchi, K Takeuchi, N Sawai, M Shiohara, T Kamijo, S Kawa, T Yamashita, A Komiyama: Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors. Blood,95, 2821-2828 (2000)
PMid:16953078
189. E Ohashi, N Miyajima, T Nakagawa, T Takahashi, H Kagechika, M Mochizuki, R Nishimura, N Sasaki: retinoids induce growth inhibition and apoptosis in mast cell tumor cell lines. J Vet Med Sci 68, 797-802 (2006)
doi:10.1292/jvms.68.797
PMid:12542529
190. M Hjertson, PK Kivinen, L Dimberg, K Nilsson, I T Harvima, G Nilsson: Retinoic acid inhibits in vitro development of mast cells but has no marked effect on mature human skin tryptase- and chymase-positive mast cells. J Investig Dermatol 120, 239-245 (2003)
doi:10.1046/j.1523-1747.2003.12030.x
PMid:14604954
191. JL Pennock, RK Grencis: In vivo exit of c-kit+/CD49dhi/{beta}7+ mucosal mast cell precursors from the bone marrow following infection with the intestinal nematode Trichinella spiralis. Blood 103, 2655-2660 (2004)
doi:10.1182/blood-2003-09-3146
PMid:1381390
192. M Gurish, A Bell, T Smith, L Ducharme, R Wang, J Weis: Expression of murine beta 7, alpha 4, and beta 1 integrin genes by rodent mast cells. J Immunol 149, 1964-1972 (1992)
193. D Artis, N Humphreys, C Potten, N Wagner, W Müller, J McDermott, R Grencis, K Else: β7 integrin-deficient mice: delayed leukocyte recruitment and attenuated protective immunity in the small intestine during enteric helminth infection. Europ J Immunol 30, 1656-1664 (2000)
doi:10.1002/1521-4141(200006)30:6<1656::AID-IMMU1656>3.0.CO;2-Z
PMid:11696590 PMCid:2195984
194. MF Gurish, H Tao, JP Abonia, A Arya, DS Friend, CM Parker, KF Austen: Intestinal mast cell progenitors require cd49dβ7 (α4β7 integrin) for tissue-specific homing. J Exp Med 194, 1243-1252 (2001)
doi:10.1084/jem.194.9.1243
PMid:15705791 PMCid:1895025
195. JP Abonia, KF Austen, BJ Rollins, SK. Joshi, RA Flavell, WA Kuziel, PA Koni, MF Gurish: Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2. Blood 105, 4308-4313 (2005)
doi:10.1182/blood-2004-09-3578
PMid:20427772
196. SJ Collington, J Hallgren, JE Pease, TG Jones, BJ Rollins, J Westwick, KF Austen, TJ Williams, MF Gurish, CL Weller: The role of the CCL2/CCR2 axis in mouse mast cell migration in vitro and in vivo. J Immunol 184, 6114-6123 (2010)
doi:10.4049/jimmunol.0904177
PMid:16670268 PMCid:1895513
197. JP Abonia, J Hallgren, T Jones, T Shi, Y Xu, P Koni, RA Flavell, JA Boyce, KF Austen, MF Gurish: Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung. Blood 108, 1588-1594 (2006)
doi:10.1182/blood-2005-12-012781
PMid:18077323 PMCid:2154456
198. J Hallgren, TG Jones, JP Abonia, W Xing, A Humbles, KF Austen, MF Gurish: Pulmonary CXCR2 regulates VCAM-1 and antigen-induced recruitment of mast cell progenitors. PNAS(USA) 104, 20478-20483 (2007)
doi:10.1073/pnas.0709651104
PMid:9862668
199. AR Rosenkranz, A Coxon, M Maurer, MF Gurish, KF Austen, DS Friend, SJ Galli, TN Mayadas: Cutting Edge: Impaired mast cell development and innate immunity in Mac-1 (CD11b/CD18, CR3)-deficient mice. J Immunol 161, 6463-6467 (1998)
PMid:11874475
200. M Artuc, UM Steckelings, BM Henz: Mast cell-fibroblast interactions: human mast cells as source and inducers of fibroblast and epithelial growth factors. J Invest Dermatol 118, 391-395 (2002)
doi:10.1046/j.0022-202x.2001.01705.x
PMid:15951536 PMCid:1774631
doi:10.1016/j.tcb.2005.09.002
PMid:16202600
202. I Puxeddu, AM Piliponsky, I Bachelet, F Levi-Schaffer: Mast cells in allergy and beyond. Internat J Biochem Cell Biol 35, 1601-1607 (2003)
doi:10.1016/S1357-2725(03)00208-5
203. B Shakoory, SM Fitzgerald, SA Lee, DS Chi, G Krishnaswamy: The role of human mast cell-derived cytokines in eosinophil biology. Jf Interferon Cytokine Res 24(5), 271-281 (2004)
doi:10.1089/107999004323065057
204. BL Gruber, MJ Marchese, RR Kew: Transforming growth factor-beta 1 mediates mast cell chemotaxis. J Immunol 152, 5860-5867 (1994)
PMid:7515916
205. A Pietrzak, A Misiak-Tloczek, E Brzezinska-Blaszczyk: Interleukin (IL)-10 inhibits RANTES-, tumour necrosis factor (TNF)- and nerve growth factor (NGF)-induced mast cell migratory response but is not a mast cell chemoattractant. Immunology Letters, 123, 46-51 (2009)
doi:10.1016/j.imlet.2009.02.003
PMid:19428551
206. N. Olsson, E. Piek, P. ten Dijke and G. Nilsson: Human mast cell migration in response to members of the transforming growth factor-beta family. J Leukoc Biol 67, 350-356 (2000)
PMid:10733095
207. N Olsson, E Piek, M Sundström, PT Dijke, G Nilsson: Transforming growth factor-(beta)-mediated mast cell migration depends on mitogen-activated protein kinase activity. Cell Signalling 13, 483-490 (2001)
doi:10.1016/S0898-6568(01)00176-0
208. KA Lindstedt, Y Wang, N Shiota, J Saarinen, M Hytiainen, JO Kokkonen, J Kenski-oja, PT Kovanen: Activation of paracrine TGF-Β1 signaling upon stimulation and degranulation of rat serosal mast cells: a novel function for chymase. FASEB J, 15, 1377-1388 (2001)
doi:10.1096/fj.00-0273com
PMid:11387235
209. CL Weller, SJ Collington, JK Brown, HRP Miller, A Al-Kashi, P Clark, PJ Jose, A Hartnell, TJ Williams: Leukotriene B4, an activation product of mast cells, is a chemoattractant for their progenitors. J Exp Med 201, 1961-1971 (2005)
doi:10.1084/jem.20042407
PMid:15955837 PMCid:2212026
210. H Ohnishi, N Miyahara, EW Gelfand: The role of leukotrieneB4 in allergic diseases. Allerg Intl 57, 291-298 (2008)
doi:10.2332/allergolint.08-RAI-0019
PMid:18797182
211. CL Weller, SJ Collington, A Hartnell, DM Conroy, T Kaise, JE Barker, MS Wilson, GW Taylor, PJ Jose, TJ Williams: Chemotactic action of prostaglandin E2 on mouse mast cells acting via the PGE2 receptor 3. PNAS(USA) 104, 11712-11717 (2007)
doi:10.1073/pnas.0701700104
PMid:17606905 PMCid:1913869
212. G Nilsson, J Butterfield, K Nilsson, A Siegbahn: Stem cell factor is a chemotactic factor for human mast cells. J Immunol 153, 3717-3723 (1994)
PMid:7523504
213. P Valent: The riddle of the mast cell: kit(CD117)-ligand as the missing link? Immunol Today 15, 111-114 (1994)
doi:10.1016/0167-5699(94)90153-8
214. S Galli, M Tsai, B Wershil: The c-kit receptor, stem cell factor, and mast cells. What each is teaching us about the others. Am J Pathol 142, 965-974 (1993)
PMid:7682764 PMCid:1886888
215. C Meininger, H Yano, R Rottapel, A Bernstein, K Zsebo, B Zetter: The c-kit receptor ligand functions as a mast cell chemoattractant. Blood 79(4), 958-963 (1992)
PMid:1371080
216. N Matsuura, BR Zetter: Stimulation of mast cell chemotaxis by interleukin 3. J Exp Med 170, 1421-1426 (1989)
doi:10.1084/jem.170.4.1421
PMid:2794861
217. S Mattoli, V Ackerman, E Vittori, M Marini: Mast cell chemotactic activity of RANTES. Biochem Biophys Res Com 209, 316-321 (1995)
doi:10.1006/bbrc.1995.1505
PMid:7537040
218. E Brzezińska-Błaszczyk, A Pietrzak, AH Misiak-Tłoczek: Tumor Necrosis Factor (TNF) is a potent rat mast cell chemoattractant. J Interferon Cytokine Res 27, 911-920 (2007)
doi:10.1089/jir.2006.0158
219. P Conti, M Reale, RC Barbacane, R Letourneau, TC Theoharides: Intramuscular injection of hrRANTES causes mast cell recruitment and increased transcription of histidine decarboxylase in mice: lack of effects in genetically mast cell-deficient W/WV mice. FASEB J 12, 1693-1700 (1998)
PMid:9837859
220. P Conti, M Reale, RC Barbacane, M Felaco, A Grilli, TC Theoharides: Mast cell recruitment after subcutaneous injection of RANTES in the sole of the rat paw. British J Haematol 103, 798-803 (1998)
doi:10.1046/j.1365-2141.1998.01060.x
PMid:9858235
221. D Taub, J Dastych, N Inamura, J Upton, D Kelvin, D Metcalfe, J Oppenheim: Bone marrow-derived murine mast cells migrate, but do not degranulate, in response to chemokines. J Immunol 154, 2393-2402 (1995)
PMid:7532669
222. J Sawada, A Itakura, A Tanaka, T Furusaka, H Matsuda: Nerve growth factor functions as a chemoattractant for mast cells through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Blood 95, 2052-2058 (2000)
PMid:10706874
223. G Nilsson, JA Mikovits, DD Metcalfe, DD Taub: Mast cell migratory response to interleukin-8 is mediated through interaction with chemokine receptor CXCR2/Interleukin-8RB. Blood 93, 2791-2797 (1999)
PMid:10216072
224. CE Brightling, A J Ammit, D Kaur, JL Black, AJ Wardlaw, JM Hughes, P Bradding: The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med 171, 1103-1108 (2005)
doi:10.1164/rccm.200409-1220OC
PMid:15879427
225. K Hartmann, BM Henz, S Kruger-Krasagakes, J Kohl, R Burger, S Guhl, I Haase, U Lippert, T Zuberbier: C3a and C5a stimulate chemotaxis of human mast cells. Blood 89, 2863-2870 (1997)
PMid:9108406
226. N Olsson, A Siegbahn, G Nilsson: Serum amyloid a induces chemotaxis of human mast cells by activating a pertussis toxin-sensitive signal transduction pathway. BiochemBiophys Res Com 254, 143-146 (1999)
doi:10.1006/bbrc.1998.9911
PMid:9920747
227. T Fujimoto, Y Sato, N Sasaki, R Teshima, K Hanaoka, S Kitani: The canine mast cell activation via CRP. Biochem Biophys Research Com 301, 212-217 (2003)
doi:10.1016/S0006-291X(02)03009-7
228. F Niyonsaba, K Iwabuchi, A Someya, M Hirata, H Matsuda, H Ogawa, I Nagaoka: A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106(1), 20-26 (2002)
doi:10.1046/j.1365-2567.2002.01398.x
PMid:11972628 PMCid:1782699
229. F Niyonsaba, K Iwabuchi, H Matsuda, H Ogawa, I Nagaoka: Epithelial cell-derived human β-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Internat Immunol 14, 421-426 (2002)
doi:10.1093/intimm/14.4.421
PMid:11934878
230. H Thompson, P Burbelo, Y Yamada, H Kleinman, D Metcalfe: Mast cells chemotax to laminin with enhancement after IgE-mediated activation. J Immunol 143, 4188-4192 (1989)
PMid:2592771