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Gene Review

CSF1  -  colony stimulating factor 1 (macrophage)

Homo sapiens

Synonyms: CSF-1, Lanimostim, M-CSF, MCSF, MGC31930, ...
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Disease relevance of CSF1


Psychiatry related information on CSF1


High impact information on CSF1

  • We now report that E5 can cooperate with human EGF receptors and with human CSF-1 receptors to induce cellular transformation of NIH 3T3 cells [9].
  • Similarities in chromosomal localization, organization, and encoded amino acid sequences suggest that the genes encoding the CSF-1 and PDGF receptors arose through duplication [10].
  • Like the v-fms oncogene product, receptors bearing the activating mutation retained high-affinity binding sites for CSF-1 but were retarded in transport to the cell surface and were phosphorylated on tyrosine in the absence of ligand [11].
  • Although the activating mutation does not affect the CSF-1 binding site in the receptor extracellular domain, it must induce a conformational change that mimics the effect of ligand binding, resulting in CSF-1-independent signals for cell growth [11].
  • We show that the human c-fms gene stimulates growth of mouse NIH 3T3 cells in agar in response to human recombinant CSF-1, indicating that receptor transduction is sufficient to induce a CSF-1 responsive phenotype [12].

Chemical compound and disease context of CSF1

  • Furthermore, the increase in PC turnover induced by CSF-1 was sensitive to pertussis toxin [13].
  • Co-expression of M-CSF transcripts and protein, FMS (M-CSF receptor) transcripts and protein, and steroid receptor content in adenocarcinomas of the ovary [14].
  • These data indicate that M-CSF does not act as a regulator of bone turnover, but GM-CSF may cause bone resorption by stimulating the synthesis of PGE2 in bone [15].
  • Furthermore, the product of the proto-oncogene fms (c-fms) may be related or identical to the receptor for macrophage colony-stimulating factor (CSF-1). v-fms is the transforming gene of the McDonough strain of feline sarcoma virus (SM-FeSV) and belongs to the family of src-related oncogenes which have tyrosine-specific kinase activity [16].
  • Pretreatment of THP-1 cells with pertussis toxin inhibited the increase in PKC activity but not the induction of TNF transcripts by M-CSF [17].

Biological context of CSF1

  • We confirm that translocations involving 1p13 are present in a majority of cases of TGCT and PVNS and show that CSF1 is the gene at the chromosome 1p13 breakpoint [18].
  • Formation of sequences by both BRG1 and the Z-DNA is required for effective chromatin remodeling of the CSF1 promoter [19].
  • Dosage analysis at the CSF1 and CSF1R loci in a new case of partial trisomy 5q [20].
  • The biologically active form of M-CSF is a disulfide-linked dimer that activates an intrinsic tyrosine kinase activity on the M-CSF receptor by inducing dimerization of the receptor molecules [21].
  • Because CSF-1 regulates the survival, proliferation and chemotaxis of macrophages and supports their activation, this factor is involved in the pathogenesis of several diseases [22].

Anatomical context of CSF1


Associations of CSF1 with chemical compounds

  • Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml [25].
  • CSF-1 was synthesized as an integral transmembrane glycoprotein that was rapidly dimerized through disulfide bonds [26].
  • The comparative stability of M-CSF mRNA from cord versus adult MNCs was next determined by actinomycin D decay studies [27].
  • These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation [28].
  • There was a significant increase in the induction of M-CSF mRNA by CHX treatment in both cord and adult MNCs [27].
  • Activation of WASP in response to treatment with CSF-1 was also shown to be phosphatidylinositol 3-kinase-dependent [29].

Physical interactions of CSF1

  • The reduction in CSF-1-binding activity was reversed by prolonged incubation at 37 degrees C even in the presence of TNF [30].
  • Furthermore, gel-shift analysis of APL cells showed elevated levels of PU.1 binding activity to the M-CSF receptor promoter, particularly after ATRA stimulation [31].
  • CONCLUSIONS: MM and M-CSF-induced VSMC killing requires MM binding to VSMC mediated by Mac-1 and ICAM-1, and Fas-FasL interaction [32].

Enzymatic interactions of CSF1


Co-localisations of CSF1

  • CD68+ monocytes and M-CSF+ fibroblast-like synoviocytes were colocalized in regions adjacent to the destroyed bone of RA patients [36].

Regulatory relationships of CSF1

  • The present studies demonstrate that the granulocyte-macrophage colony-stimulating factor (GM-CSF) also induces CSF-1 transcripts in monocytes [37].
  • NIH 3T3 cells cotransfected with the human c-fms proto-oncogene together with a 1.6-kilobase cDNA clone encoding a 256-amino-acid precursor of the human mononuclear phagocyte colony-stimulating factor CSF-1 (M-CSF) undergo transformation by an autocrine mechanism [26].
  • The ligand for flt-3 (FLT3L) exhibits striking structural homology with stem cell factor (SCF) and monocyte colony-stimulating factor (M-CSF) and also acts in synergy with a range of other hematopoietic growth factors (HGF) [38].
  • Network formation by these HUVECs after treatment with supernatants from monocytes stimulated with M-CSF were inhibited by anti-VEGF, but not by the isogenic control, Abs [39].
  • We have previously shown that a low concentration of CSF-1 (1 U/ml) can trigger human immature monocytic progenitor proliferation in the presence of low concentrations of IL3 (1.7 U/ml) [40].

Other interactions of CSF1

  • Accumulation of CSF-1 mRNA is observed only in NK cells stimulated with both CD16 ligands and rIL-2, whereas accumulation of IL-3 mRNA is observed only in NK cells stimulated with PDBu/A23187 [24].
  • The effects of CSF-1 are mediated through binding to specific, high-affinity surface receptors encoded by the c-fms gene [3].
  • Terminal granulocytic or monocytic differentiation was observed when AML-193 cells were treated with RA and G-CSF, or D3 and M-CSF, respectively, as evaluated by cell morphology, analysis of surface antigens, and phagocytic functions [41].
  • When the addition of IL-6 to M-CSF-supplemented cultures was delayed for more than one day after the beginning of culture, enhancement of macrophage colony formation was lost [42].
  • (5) When cultured in the presence of M-CSF and IL-4, UG3 cells differentiate into osteoclast-like multinucleated giant cells capable of bone resorption and display tartrate-resistant acid phosphatase (TRAP) activity [43].

Analytical, diagnostic and therapeutic context of CSF1

  • The structure of a recombinant human M-CSF dimer, determined at 2.5 angstroms by x-ray crystallography, contains two bundles of four alpha helices laid end-to-end, with an interchain disulfide bond [21].
  • CSF-1 and c-fms gene expression was investigated in fresh human acute myeloblastic leukemic cells by Northern blot hybridization using cDNA probes [3].
  • In response to both adhesion and recombinant human GM-CSF (rhGM-CSF) stimulation for 120 hours, radioimmunoassays and bioassays showed that cord MNCs produced twofold to threefold less M-CSF protein compared with adult MNCs [27].
  • Although M-CSF has been used for myelosuppression due to chemotherapy in patients with solid tumors, the effect of exogenous M-CSF on tumor angiogenesis has not been studied [44].
  • RT-PCR analysis of cytokine and growth factor mRNA in MSCs and MDSCs revealed a very similar pattern of mRNAs including IL-6, -7, -8, -11, -12, -14, and -15, M-CSF, Flt-3 ligand, and SCF [45].


  1. Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Koyanagi, Y., O'Brien, W.A., Zhao, J.Q., Golde, D.W., Gasson, J.C., Chen, I.S. Science (1988) [Pubmed]
  2. Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. Firestein, G.S., Xu, W.D., Townsend, K., Broide, D., Alvaro-Gracia, J., Glasebrook, A., Zvaifler, N.J. J. Exp. Med. (1988) [Pubmed]
  3. Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells. Rambaldi, A., Wakamiya, N., Vellenga, E., Horiguchi, J., Warren, M.K., Kufe, D., Griffin, J.D. J. Clin. Invest. (1988) [Pubmed]
  4. Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders. Pettenati, M.J., Le Beau, M.M., Lemons, R.S., Shima, E.A., Kawasaki, E.S., Larson, R.A., Sherr, C.J., Diaz, M.O., Rowley, J.D. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  5. Genetic association study on colony-stimulating factor 1 in Alzheimer's disease. Wollmer, M.A., Nitsch, R.M., Hock, C., Papassotiropoulos, A. Neuro-degenerative diseases (2006) [Pubmed]
  6. Colony-stimulating factor-1 expression in the human fetus and newborn. Roth, P., Stanley, E.R. J. Leukoc. Biol. (1995) [Pubmed]
  7. Immunohistochemical detection of cells positive for colony-stimulating factor 1 in lymph nodes from reactive lymphadenitis, and Hodgkin's disease. Moreau, A., Praloran, V., Berrada, L., Coupey, L., Gaillard, F. Leukemia (1992) [Pubmed]
  8. Low serum M-CSF levels are associated with unexplained recurrent abortion. Katano, K., Matsumoto, Y., Ogasawara, M., Aoyama, T., Ozaki, Y., Kajiura, S., Aoki, K. Am. J. Reprod. Immunol. (1997) [Pubmed]
  9. The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF-1 receptors. Martin, P., Vass, W.C., Schiller, J.T., Lowy, D.R., Velu, T.J. Cell (1989) [Pubmed]
  10. Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes. Roberts, W.M., Look, A.T., Roussel, M.F., Sherr, C.J. Cell (1988) [Pubmed]
  11. A point mutation in the extracellular domain of the human CSF-1 receptor (c-fms proto-oncogene product) activates its transforming potential. Roussel, M.F., Downing, J.R., Rettenmier, C.W., Sherr, C.J. Cell (1988) [Pubmed]
  12. Transforming potential of the c-fms proto-oncogene (CSF-1 receptor). Roussel, M.F., Dull, T.J., Rettenmier, C.W., Ralph, P., Ullrich, A., Sherr, C.J. Nature (1987) [Pubmed]
  13. Colony-stimulating factor 1 activates protein kinase C in human monocytes. Imamura, K., Dianoux, A., Nakamura, T., Kufe, D. EMBO J. (1990) [Pubmed]
  14. Co-expression of M-CSF transcripts and protein, FMS (M-CSF receptor) transcripts and protein, and steroid receptor content in adenocarcinomas of the ovary. Kommoss, F., Wölfle, J., Bauknecht, T., Pfisterer, J., Kiechle-Schwarz, M., Pfleiderer, A., Sauerbrei, W., Kiehl, R., Kacinski, B.M. J. Pathol. (1994) [Pubmed]
  15. Differential activity of granulocyte-macrophage and macrophage colony stimulating factors on bone resorption in fetal rat long bone organ cultures. Bertolini, D.R., Strassmann, G. Cytokine (1991) [Pubmed]
  16. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Coussens, L., Van Beveren, C., Smith, D., Chen, E., Mitchell, R.L., Isacke, C.M., Verma, I.M., Ullrich, A. Nature (1986) [Pubmed]
  17. Functional expression of the macrophage colony-stimulating factor receptor in human THP-1 monocytic leukemia cells. Datta, R., Imamura, K., Goldman, S.J., Dianoux, A.C., Kufe, D.W., Sherman, M.L. Blood (1992) [Pubmed]
  18. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. West, R.B., Rubin, B.P., Miller, M.A., Subramanian, S., Kaygusuz, G., Montgomery, K., Zhu, S., Marinelli, R.J., De Luca, A., Downs-Kelly, E., Goldblum, J.R., Corless, C.L., Brown, P.O., Gilks, C.B., Nielsen, T.O., Huntsman, D., van de Rijn, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  19. Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling. Liu, H., Mulholland, N., Fu, H., Zhao, K. Mol. Cell. Biol. (2006) [Pubmed]
  20. Dosage analysis at the CSF1 and CSF1R loci in a new case of partial trisomy 5q. Genuardi, M., Flamia, R., Palka, G., Parruti, G., Neri, G. Clin. Genet. (1992) [Pubmed]
  21. Three-dimensional structure of dimeric human recombinant macrophage colony-stimulating factor. Pandit, J., Bohm, A., Jancarik, J., Halenbeck, R., Koths, K., Kim, S.H. Science (1992) [Pubmed]
  22. CSF-1 regulation of the wandering macrophage: complexity in action. Pixley, F.J., Stanley, E.R. Trends Cell Biol. (2004) [Pubmed]
  23. Reassignment of the human ARH9 RAS-related gene to chromosome 1p13-p21. Morris, S.W., Valentine, M.B., Kirstein, M.N., Huebner, K. Genomics (1993) [Pubmed]
  24. Production of hematopoietic colony-stimulating factors by human natural killer cells. Cuturi, M.C., Anegón, I., Sherman, F., Loudon, R., Clark, S.C., Perussia, B., Trinchieri, G. J. Exp. Med. (1989) [Pubmed]
  25. Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. Mustafa, M.M., Lebel, M.H., Ramilo, O., Olsen, K.D., Reisch, J.S., Beutler, B., McCracken, G.H. J. Pediatr. (1989) [Pubmed]
  26. Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes. Rettenmier, C.W., Roussel, M.F., Ashmun, R.A., Ralph, P., Price, K., Sherr, C.J. Mol. Cell. Biol. (1987) [Pubmed]
  27. Decreased macrophage colony-stimulating factor mRNA expression from activated cord versus adult mononuclear cells: altered posttranscriptional stability. Suen, Y., Lee, S.M., Schreurs, J., Knoppel, E., Cairo, M.S. Blood (1994) [Pubmed]
  28. Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor-mediated agonists. Yuo, A., Kitagawa, S., Motoyoshi, K., Azuma, E., Saito, M., Takaku, F. Blood (1992) [Pubmed]
  29. The mechanism of CSF-1-induced Wiskott-Aldrich syndrome protein activation in vivo: a role for phosphatidylinositol 3-kinase and Cdc42. Cammer, M., Gevrey, J.C., Lorenz, M., Dovas, A., Condeelis, J., Cox, D. J. Biol. Chem. (2009) [Pubmed]
  30. Modulation of colony-stimulating factor-1 receptors on macrophages by tumor necrosis factor. Shieh, J.H., Peterson, R.H., Warren, D.J., Moore, M.A. J. Immunol. (1989) [Pubmed]
  31. C-fms expression correlates with monocytic differentiation in PML-RAR alpha+ acute promyelocytic leukemia. Riccioni, R., Saulle, E., Militi, S., Sposi, N.M., Gualtiero, M., Mauro, N., Mancini, M., Diverio, D., Lo Coco, F., Peschle, C., Testa, U. Leukemia (2003) [Pubmed]
  32. Mac-1 and Fas activities are concurrently required for execution of smooth muscle cell death by M-CSF-stimulated macrophages. Vasudevan, S.S., Lopes, N.H., Seshiah, P.N., Wang, T., Marsh, C.B., Kereiakes, D.J., Dong, C., Goldschmidt-Clermont, P.J. Cardiovasc. Res. (2003) [Pubmed]
  33. C-fms protein expression by B-cells, with particular reference to the hairy cells of hairy-cell leukaemia. Till, K.J., Lopez, A., Slupsky, J., Cawley, J.C. Br. J. Haematol. (1993) [Pubmed]
  34. CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2. Husson, H., Mograbi, B., Schmid-Antomarchi, H., Fischer, S., Rossi, B. Oncogene (1997) [Pubmed]
  35. Nitric oxide inhibits macrophage-colony stimulating factor gene transcription in vascular endothelial cells. Peng, H.B., Rajavashisth, T.B., Libby, P., Liao, J.K. J. Biol. Chem. (1995) [Pubmed]
  36. Nurse-like cells from patients with rheumatoid arthritis support the survival of osteoclast precursors via macrophage colony-stimulating factor production. Tsuboi, H., Udagawa, N., Hashimoto, J., Yoshikawa, H., Takahashi, N., Ochi, T. Arthritis Rheum. (2005) [Pubmed]
  37. Expression of the macrophage-specific colony-stimulating factor in human monocytes treated with granulocyte-macrophage colony-stimulating factor. Horiguchi, J., Warren, M.K., Kufe, D. Blood (1987) [Pubmed]
  38. Increased recruitment of hematopoietic progenitor cells underlies the ex vivo expansion potential of FLT3 ligand. Haylock, D.N., Horsfall, M.J., Dowse, T.L., Ramshaw, H.S., Niutta, S., Protopsaltis, S., Peng, L., Burrell, C., Rappold, I., Buhring, H.J., Simmons, P.J. Blood (1997) [Pubmed]
  39. M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes. Eubank, T.D., Galloway, M., Montague, C.M., Waldman, W.J., Marsh, C.B. J. Immunol. (2003) [Pubmed]
  40. IL-3, GM-CSF and CSF-1 modulate c-fms mRNA more rapidly in human early monocytic progenitors than in mature or transformed monocytic cells. Panterne, B., Hatzfeld, A., Sansilvestri, P., Cardoso, A., Monier, M.N., Batard, P., Hatzfeld, J. J. Cell. Sci. (1996) [Pubmed]
  41. Two-step differentiation of AML-193 leukemic line: terminal maturation is induced by positive interaction of retinoic acid with granulocyte colony-stimulating factor (CSF) and vitamin D3 with monocyte CSF. Valtieri, M., Boccoli, G., Testa, U., Barletta, C., Peschle, C. Blood (1991) [Pubmed]
  42. Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells. Bot, F.J., van Eijk, L., Broeders, L., Aarden, L.A., Löwenberg, B. Blood (1989) [Pubmed]
  43. A new cytokine-dependent monoblastic cell line with t(9;11)(p22;q23) differentiates to macrophages with macrophage colony-stimulating factor (M-CSF) and to osteoclast-like cells with M-CSF and interleukin-4. Ikeda, T., Sasaki, K., Ikeda, K., Yamaoka, G., Kawanishi, K., Kawachi, Y., Uchida, T., Takahara, J., Irino, S. Blood (1998) [Pubmed]
  44. Macrophage colony-stimulating factor induces vascular endothelial growth factor production in skeletal muscle and promotes tumor angiogenesis. Okazaki, T., Ebihara, S., Takahashi, H., Asada, M., Kanda, A., Sasaki, H. J. Immunol. (2005) [Pubmed]
  45. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. Majumdar, M.K., Thiede, M.A., Mosca, J.D., Moorman, M., Gerson, S.L. J. Cell. Physiol. (1998) [Pubmed]
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