The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the placenta.[5]
Structure
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.[5]
Four transcript variants encoding three different isoforms (a proteoglycan, glycoprotein and cell surface protein)[6] have been found for this gene.[5]
Function
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.[7] M-CSF affects macrophages and monocytes in several ways, including stimulating increased phagocytic and chemotactic activity, and increased tumour cell cytotoxicity.[8]
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.[9]
M-CSF released by osteoblasts (as a result of endocrine stimulation by parathyroid hormone) exerts paracrine effects on osteoclasts.[10] 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 trophoblastic 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.[11]
Clinical significance
Locally produced M-CSF in the vessel wall contributes to the development and progression of atherosclerosis.[12]
M-CSF has been described to play a role in renal pathology including acute kidney injury and chronic kidney failure.[13][14] The chronic activation of monocytes can lead to multiple metabolic, hematologic and immunologic abnormalities in patients with chronic kidney failure.[13] In the context of acute kidney injury, M-CSF has been implicated in promoting repair following injury,[15] but also been described in an opposing role, driving proliferation of a pro-inflammatory macrophage phenotype.[16]
^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. PMID14709771. S2CID30541196.
Stanley ER, Berg KL, Einstein DB, Lee PS, Yeung YG (1995). "The biology and action of colony stimulating factor-1". Stem Cells. 12 (Suppl 1): 15–24, discussion 25. PMID7696959.
Alterman RL, Stanley ER (1994). "Colony stimulating factor-1 expression in human glioma". Molecular and Chemical Neuropathology. 21 (2–3): 177–88. doi:10.1007/BF02815350. PMID8086034. S2CID12846642.
Sweet MJ, Hume DA (2004). "CSF-1 as a regulator of macrophage activation and immune responses". Archivum Immunologiae et Therapiae Experimentalis. 51 (3): 169–77. PMID12894871.
Saltman DL, Dolganov GM, Hinton LM, Lovett M (February 1992). "Reassignment of the human macrophage colony stimulating factor gene to chromosome 1p13-21". Biochemical and Biophysical Research Communications. 182 (3): 1139–43. doi:10.1016/0006-291X(92)91850-P. PMID1540160.
Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER (July 1985). "The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1". Cell. 41 (3): 665–76. doi:10.1016/S0092-8674(85)80047-7. PMID2408759. S2CID32037918.
Cerretti DP, Wignall J, Anderson D, Tushinski RJ, Gallis BM, Stya M, Gillis S, Urdal DL, Cosman D (August 1988). "Human macrophage-colony stimulating factor: alternative RNA and protein processing from a single gene". Molecular Immunology. 25 (8): 761–70. doi:10.1016/0161-5890(88)90112-5. PMID2460758.
Takahashi M, Hirato T, Takano M, Nishida T, Nagamura K, Kamogashira T, Nakai S, Hirai Y (June 1989). "Amino-terminal region of human macrophage colony-stimulating factor (M-CSF) is sufficient for its in vitro biological activity: molecular cloning and expression of carboxyl-terminal deletion mutants of human M-CSF". Biochemical and Biophysical Research Communications. 161 (2): 892–901. doi:10.1016/0006-291X(89)92683-1. PMID2660794.
Kawasaki ES, Ladner MB, Wang AM, Van Arsdell J, Warren MK, Coyne MY, Schweickart VL, Lee MT, Wilson KJ, Boosman A (October 1985). "Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1)". Science. 230 (4723): 291–6. Bibcode:1985Sci...230..291K. doi:10.1126/science.2996129. PMID2996129.
Takahashi M, Hong YM, Yasuda S, Takano M, Kawai K, Nakai S, Hirai Y (May 1988). "Macrophage colony-stimulating factor is produced by human T lymphoblastoid cell line, CEM-ON: identification by amino-terminal amino acid sequence analysis". Biochemical and Biophysical Research Communications. 152 (3): 1401–9. doi:10.1016/S0006-291X(88)80441-8. PMID3259875.
