|Cell Proliferation Induced by M‑CSF and Neutralization by Mouse M‑CSF Antibody. Recombinant Mouse M‑CSF (Catalog # 416-ML) stimulates proliferation in the M‑NFS‑60 mouse myelogenous leukemia lymphoblast cell line in a dose-dependent manner (orange line). Proliferation elicited by Recombinant Mouse M‑CSF (10 ng/mL) is neutralized (green line) by increasing concentrations of Goat Anti-Mouse M‑CSF Polyclonal Antibody (Catalog # AB-416-NA). The ND50 is typically 0.2‑0.6 µg/mL.|
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 mouse M-CSF 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 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 that is necessary and sufficient for interaction with the M-CSF receptor (10, 11). The first 229 aa of mature mouse M-CSF shares 87%, 83%, 82% and 81% aa identity with corresponding regions of rat, dog, cow and human M-CSF, respectively (12, 13). Human M‑CSF is active in the mouse, but mouse M-CSF is reported to be species-specific.
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