[Frontiers in Bioscience S3, 467-473, January 1, 2011]

Modulation of hematopoiesis through histamine receptor signaling

Elke Schneider, Anne-France Bertron and Michel Dy

Universite Paris Descartes, Faculte de Medecine,- CNRS UMR8147 Cytokines, Hematopoiesis and Immune Response, Hospital Necker - 161 rue de Sevres, Paris, France


1. Abstract
2. Introduction
3. Modulation of hematopoiesis by endogenous and exogenous histamine
4. Evidence for a functional H4 histamine receptor (H4R) in hematopoietic progenitor subsets
4.1. H4R mRNA and protein expression in murine and human hematopoietic progenitor cells
4.2. H4R-mediated blockade of growth factor-induced entry of hematopoietic progenitors into cell cycle
5. Histamine receptor signaling
5.1. cAMP/PKA-dependent cycle arrest in response to H4R activation
5.2. Cell cycle arrest through H4R-induced maintenance of p21Cip1/Waf1 expresssion
6. H4R-induced cycle arrest: a means of myeloprotection
6.1. H4R-mediated in vitro and in vivo protection of hematopoietic progenitor cells against the toxicity of anti-cancer drugs
6.2. Lack of H4R expression and function in common carcinoma cell lines.
7. Conclusions and perspectives
8. Acknowledgment
9. References


Histamine is one of the most versatile biogenic amines targeting a variety of cells through extra- and intracellular binding sites and specific receptors, which trigger different signal transduction pathways. It has been associated with cell growth ever since G. Kahlson demonstrated that its synthesis was increased in rapidly growing tissues of plants and animals. He proposed that the newly formed amine, as opposed to its stored counterpart, might play a major role in growth processes. Later on, a number of investigators provided evidence for the contribution of histamine to the expansion of normal and malignant cells, whether of hematopoietic origin or not. These studies have generated conflicting results, revealing growth-promoting as well as inhibitory effects, most likely because the final outcome of exposure to histamine depends on the signaling pathways triggered by distinct receptors and their differential distribution among the target population. The purpose of the present review is to outline our current understanding of the regulatory functions of histamine during growth and differentiation of hematopoietic progenitors, focusing on those mediated through its H4 receptor.