M-CSF

M-CSF, also known as CSF1, is a four-α-helicalbundle 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 M-CSF include fibroblasts, activated macrophages, endometrial secretory epithelium, bone marrow stromal cells and activated endothelial cells. The MCSF receptor (cfms) transduces its pleotropic effects and mediates its endocytosis. M-CSF mRNAs of various sizes occur. Full length human MCSF transcripts encode a 522 amino acid (aa) type I transmembrane (TM) protein with a 464 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 N-and O-glycosylated 86 kDa dimer, while the other is modified by both glycosylation and chondroitinsulfate proteoglycan (PG) to generate a 200 kDa subunit. Although PG-modified 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 halflife, all contain the N-terminal 150 aa portion that is necessary and sufficient for interaction with the M-CSF receptor. The first 223 aa of mature human M-CSF shares 88%, 86%, 81% and 74% aa identity with corresponding regions of dog, cow, mouse and rat M-CSF, respectively. Human M-CSF is active in the mouse, but mouse M-CSF is reported to be species-specific.