Survival of monocytes and macrophages and their role in health and disease
Melissa Hunter1, Yijie Wang1, Tim Eubank1, Christopher Baran1, Patrick Nana-Sinkam1, Clay Marsh1
1
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine and the Center for Critical Care Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. Cytokines and non-cytokines that activate monocyte/macrophage survival
- 3.1. GM-CSF and IL-3 as monocyte survival factors
- 3.2. ROS/LPS
- 3.3. Expression and function of the M-CSF receptor
- 4. Signaling pathways activated by M-CSF to regulate cell survival
- 4.1. Role of Akt in monocyte/macrophage survival
- 4.2. Role of MAPK family members in monocyte/macrophage survival
- 4.3. Other signaling pathways activated by M-CSF
- 5. Transcription factors downstream of M-CSF activation
- 5.1. Role of NF-k
B in monocyte/macrophage survival
- 5.2. Ets transcription factors
- 6. Phosphatases that regulate monocyte/macrophage survival
- 6.1. SHIP1
- 6.2. SHIP2
- 6.3. PTEN
- 6.4. SHP-1
- 7. Murine models of disease related to mononuclear phagocyte biology
- 7.1. Murine models deficient in macrophages
- 7.1.1. M-CSF-/- and M-CSF receptor null models
- 7.1.2. PU.1 deficient mice
- 7.2. Models of enhanced macrophage trafficking
- 7.2.1. SHIP deficient mouse models
- 7.2.2. Myr-Akt1 mouse model
- 7.3. Murine models of human disease
- 7.3.1. Pulmonary fibrosis
- 7.3.2. Atherosclerosis
- 7.3.3. Breast cancer
- 8. Aberrant M-CSF expression and/or receptor activation in human disease and its influence on cell survival
- 8.1. Idiopathic pulmonary fibrosis
- 8.2. Lung cancer
- 8.3. Breast cancer
- 8.4. Coronary heart disease
- 8.5. M-CSFR mutation in megakaryocytic leukemia
- 9. Discussion
- 10. Acknowledgments
- 11. References
1. ABSTRACT
Macrophages are versatile cells involved in health and disease. These cells act as scavengers to rid the body of apoptotic and senescent cells and debris through their phagocytic function. Although this is a primary function of these cells, macrophages play vital roles in inflammation and repair of damaged tissue. Macrophages secrete a large number of cytokines, chemokines and growth factors that recruit and activate a variety of cell types to inflamed tissue compartments. These cells are also critical in cell-mediated immunity and in the resolution of inflammation. Since macrophages, and their precursors, blood monocytes, are important in regulating and resolving inflammation, prolonged cellular survival in tissue compartments could be detrimental. Thus, factors that regulate the fate of monocyte and macrophage survival are important in cellular homeostasis. In this article, we will explore stimuli and the intracellular pathways important in regulating macrophage survival and implication in human disease.
