Macrophage colony-stimulating factor

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RefSeq (mRNA)



RefSeq (protein)



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M-CSF is a cytokine, being a smaller protein involved in cell signaling. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors.[1]

Four transcript variants encoding three different isoforms (a proteoglycan, glycoprotein and cell surface protein)[2] have been found for this gene.[1]


M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the proliferation, differentiation, and survival of monocytes, macrophages, and bone marrow progenitor cells.[3] M-CSF affects macrophages and monocytes in several ways, including stimulating increased phagocytic and chemotactic activity, and increased tumour cell cytotoxicity.[4] The role of M-CSF is not only restricted to the monocyte/macrophage cell lineage. By interacting with its membrane receptor (CSF1R or M-CSF-R encoded by the c-fms proto-oncogene), M-CSF also modulates the proliferation of earlier hematopoietic progenitors and influence numerous physiological processes involved in immunology, metabolism, fertility and pregnancy.[5]

M-CSF released by osteoblasts (as a result of endocrine stimulation by parathyroid hormone) exerts paracrine effects on osteoclasts.[6] M-CSF binds to receptors on osteoclasts inducing differentiation, and ultimately leading to increased plasma calcium levels—through the resorption (breakdown) of bone[citation needed]. Additionally, high levels of CSF-1 expression are observed in the endometrial epithelium of the pregnant uterus as well as high levels of its receptor CSF1R in the placental trophoblast. Studies have shown that activation of trophoblasitc CSF1R by local high levels of CSF-1 is essential for normal embryonic implantation and placental development. More recently, it was discovered that CSF-1 and its receptor CSF1R are implicated in the mammary gland during normal development and neoplastic growth.[7]

Clinical significance

Locally produced M-CSF in the vessel wall contributes to the development and progression of atherosclerosis.[8]

M-CSF has been described to play a role in renal pathology including acute kidney injury and chronic renal failure.[9][10] The chronic activation of monocytes can lead to multiple metabolic, hematologic and immunologic abnormalities in patients with chronic renal failure.[9] In the context of acute kidney injury, M-CSF has been implicated in promoting repair following injury,[11] but also been described in an opposing role, driving proliferation of a pro-inflammatory macrophage phenotype.[12]

As a drug target

PD-0360324 and MCS110 are CSF1 inhibitors in clinical trials for some cancers.[13] See also CSF1R inhibitors.


Macrophage colony-stimulating factor has been shown to interact with PIK3R2.[14]


  1. 1.0 1.1 1.2 "Entrez Gene: CSF1 colony stimulating factor 1 (macrophage)".
  2. Jang MH, Herber DM, Jiang X, Nandi S, Dai XM, Zeller G, Stanley ER, Kelley VR (September 2006). "Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation". Journal of Immunology. 177 (6): 4055–63. doi:10.4049/jimmunol.177.6.4055. PMID 16951369.
  3. Stanley ER, Berg KL, Einstein DB, Lee PS, Pixley FJ, Wang Y, Yeung YG (January 1997). "Biology and action of colony--stimulating factor-1". Molecular Reproduction and Development. 46 (1): 4–10. doi:10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V. PMID 8981357.
  4. Nemunaitis J (April 1993). "Macrophage function activating cytokines: potential clinical application". Critical Reviews in Oncology/Hematology. 14 (2): 153–71. doi:10.1016/1040-8428(93)90022-V. PMID 8357512.
  5. Fixe P, Praloran V (June 1997). "Macrophage colony-stimulating-factor (M-CSF or CSF-1) and its receptor: structure-function relationships". European Cytokine Network. 8 (2): 125–36. PMID 9262961.
  6. "Paracrine and endocrine actions of bone—the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts". Retrieved 12 July 2018.
  7. Sapi E (January 2004). "The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update". Experimental Biology and Medicine. 229 (1): 1–11. doi:10.1177/153537020422900101. PMID 14709771.
  8. Rajavashisth T, Qiao JH, Tripathi S, Tripathi J, Mishra N, Hua M, Wang XP, Loussararian A, Clinton S, Libby P, Lusis A (June 1998). "Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice". The Journal of Clinical Investigation. 101 (12): 2702–10. doi:10.1172/JCI119891. PMC 508861. PMID 9637704.
  9. 9.0 9.1 Le Meur Y, Fixe P, Aldigier JC, Leroux-Robert C, Praloran V (September 1996). "Macrophage colony stimulating factor involvement in uremic patients". Kidney International. 50 (3): 1007–12. doi:10.1038/ki.1996.402. PMID 8872977.
  10. "Acute kidney injury: CSF-1 signalling is involved in repair following AKI". Nature Reviews Nephrology. 9 (1): 2–2. 2013-01-01. doi:10.1038/nrneph.2012.253. ISSN 1759-5061.
  11. Zhang MZ, Yao B, Yang S, Jiang L, Wang S, Fan X, Yin H, Wong K, Miyazawa T, Chen J, Chang I, Singh A, Harris RC (December 2012). "CSF-1 signaling mediates recovery from acute kidney injury". The Journal of Clinical Investigation. 122 (12): 4519–32. doi:10.1172/JCI60363. PMC 3533529. PMID 23143303.
  12. Cao Q, Wang Y, Zheng D, Sun Y, Wang C, Wang XM, Lee VW, Wang Y, Zheng G, Tan TK, Wang YM, Alexander SI, Harris DC (April 2014). "Failed renoprotection by alternatively activated bone marrow macrophages is due to a proliferation-dependent phenotype switch in vivo". Kidney International. 85 (4): 794–806. doi:10.1038/ki.2013.341. PMID 24048378.
  13. Interest Builds in CSF1R for Targeting Tumor Microenvironment
  14. Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD (December 1992). "Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system". The Biochemical Journal. 288 (2): 395–405. doi:10.1042/bj2880395. PMC 1132024. PMID 1334406.

Further reading

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