M-CSF-γ (human, recombinant)

Macrophage colony-stimulating factor (M-CSF) is a glycoprotein encoded by the CSF1 gene in humans that promotes the differentiation, proliferation, and function of mononuclear phagocytes, including macrophages, osteoclasts, and dendritic cells.^1,2 Alternative splicing of CSF1 pre-mRNA produces one full-length long isoform (M-CSF-β), an intermediate-length isoform (M-CSF-γ), and a short-length isoform (M-CSF-α) that share sequence homology in the 150-amino acid receptor binding region that is required for the biological activity of M-CSF.^3,4 M-CSF exists as a disulfide-linked homodimer where each monomer contains four α-helices, an antiparallel β-sheet, and numerous glycosylation sites.¹ M-CSF is constitutively produced by many cell types, including stromal cells, osteoclasts, fibroblasts, and macrophages, and is localized to the cell surface where it can be proteolytically cleaved to yield a secreted form.^5,6 Binding of M-CSF to the M-CSF receptor, which is expressed by monocytes, macrophages, osteoclasts, and dendritic cells, promotes cell differentiation, proliferation, and survival of mononuclear phagocytes and regulates bone resorption by osteoclasts.^5,7 Mice homozygous for Csf1^op, an inactivating mutation, exhibit defects in fertility and neural development and develop osteopetrosis, a condition characterized by increased bone density.⁸ Neutralization of M-CSF with a monoclonal antibody decreases joint swelling and distortion in a mouse model of collagen-induced arthritis.⁹ Serum M-CSF levels are increased in patients with colorectal, pancreatic, prostate, or head and neck cancer.⁵ M-CSF has been used to generate bone marrow-derived macrophages with an anti-inflammatory phenotype in vitro.² Cayman's M-CSF-γ (human, recombinant) protein can be used for cell-based assay applications. This protein consist of 158 amino acids, has a calculated molecular weight of 18.4 kDa, and a predicted N-terminus of Glu37 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the molecular mass of the protein is approximately 23 kDa due to apparent post-translational modifications.

WARNING This product is not for human or veterinary use.

1. Stanley, E.R., Berg, K.L., Einstein, D.B., et al. Biology and action of colony-stimulating factor-1. Mol. Reprod. Dev. 46(1), 4-10 (1997).

2. Ushach, I., and Zlotnik, A. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J. Leukoc. Biol. 100(3), 481-489 (2016).

3. Cerretti, D.P., Wignall, J., Anderson, D., et al. Human macrophage-colony stimulating factor: Alternative RNA and protein processing from a single gene. Mol. Immunol. 25(8), 761-770 (1988).

4. Fitzgerald, K.A., Callard, R.E., O'Neill, L.A.J., et al. M-CSF. The Cytokine Factsbook and Webfacts 367-372 (2001).

5. Chockalingam, S., and Ghosh, S.S. Macrophage colony-stimulating factor and cancer: A review. Tumour Biol. 35(11), 10635-10644 (2014).

6. Hamilton, J.A. Colony-stimulating factors in inflammation and autoimmunity. Nat. Rev. Immunol. 8(7), 533-544 (2008).

7. Stanley, E.R., and Chitu, V. CSF-1 receptor signaling in myeloid cells. Cold Spring Harb. Mol. Case Stud. 6(6), a021857 (2014).

8. Dai, X.-M., Ryan, G.R., Hapel, A.J., et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood 99(1), 111-120 (2002).

9. Campbell, I.K., Rich, M.J., Bischof, R.J., et al. The colony-stimulating factors and collagen-induced arthritis: Exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF. J. Leukoc. Biol. 68(1), 144-150 (2000).