M-CSF

M-CSF, also known as CSF-1, is a four-α helical-bundle cytokine that is the primary regulator of macrophage survival, proliferation and differentiation. M-CSF is also essential for the survival and proliferation of osteoclast progenitors. M-CSF also primes and enhances macrophage killing of tumor cells and microorganisms, regulates the release of cytokines and other inflammatory modulators from macrophages, and stimulates pinocytosis. MCSF increases during pregnancy to support implantation and growth of the decidua and placenta. Sources of MCSF include fibroblasts, activated macrophages, endometrial secretory epithelium, bone marrow stromal cells, and activated endothelial cells. The M-CSF receptor (c-fms) transduces its pleotropic effects and mediates its endocytosis. M-CSF mRNAs of various sizes occur. Full length mouse MCSF transcripts encode a 520 amino acid (aa) type I transmembrane (TM) protein with a 462 aa extracellular region, a 21 aa TM domain, and a 37 aa cytoplasmic tail that forms a 140 kDa covalent dimer. Differential processing produces two proteolytically cleaved, secreted dimers. One is an Nand Oglycosylated 86 kDa dimer, while the other is modified by both glycosylation and chondroitinsulfate proteoglycan (PG) to generate a 200 kDa subunit. Although PGmodified M-CSF can circulate, it may be immobilized by attachment to type V collagen. Shorter transcripts encode M-CSF that lacks cleavage and PG sites and produces an N-glycosylated 68 kDa TM dimer and a slowly produced 44 kDa secreted dimer. Although forms may vary in activity and half-life, all contain the N-terminal 150 aa portion that is necessary and sufficient for interaction with the M-CSF receptor. The first 229 aa of mature mouse MCSF shares 87%, 83%, 82%, and 81% aa identity with corresponding regions of rat, dog, cow, and human MCSF, respectively. Human MCSF is active in the mouse, but mouse M-CSF is reported to be species-specific.