Macrophage Colony Stimulating Factor(M-CSF), also known as CSF-1, is a four-alpha -helical-bundle cytokine that is the primary regulator of macrophage survival, proliferation and differentiation [1-3]. M-CSF is also essential for the survival and proliferation of osteoclast progenitors [1, 4]. 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 [2, 3]. M-CSF increases during pregnancy to support implantation and growth of the decidua and placenta [5]. Sources of M-CSF include fibroblasts, activated macrophages, endometrial secretory epithelium, bone marrow stromal cells and activated endothelial cells [1-5]. The M-CSF receptor (c-fms) transduces its pleotropic effects and mediates its endocytosis. M-CSF mRNAs of various sizes occur [3-9]. Full length human M-CSF 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 chondroitin-sulfate 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 [8]. 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 [7]. Although forms may vary in activity and half-life, all contain the N-terminal 150 aa portion [10].
Reference
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