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Gene Review

Csf2  -  colony stimulating factor 2 (granulocyte...

Mus musculus

Synonyms: CSF, Colony-stimulating factor, Csfgm, GM-CSF, GMCSF, ...
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Disease relevance of Csf2

  • We also provide evidence to indicate that Nf1 gene loss induces myeloproliferative disease through a Ras-mediated hypersensitivity to granulocyte/macrophage-colony stimulating factor (GM-CSF) [1].
  • The effects of CSF in mice pretreated with LF were not mimicked by 0.1-100 ng E. coli lipopolysaccharide [2].
  • These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease [3].
  • We show GM-CSF to be the single most effective cytokine for enhancing both cellular and humoral immunity to two previously characterized HIV-1 MN vaccine constructs [4].
  • IFN-gamma, TNF-alpha, IL-1, and granulocyte-macrophage CSF (GM-CSF) play an important role in host resistance to infection with nontyphoid Salmonella [5].

Psychiatry related information on Csf2

  • Lymphocytes from spleens and draining lymph nodes of mice primed with Id-KLH plus GM-CSF, but not with Id-KLH alone, demonstrated significant proliferation to Id in vitro without any biased production of interferon gamma or interleukin 4 protein or mRNA [6].
  • These results demonstrate the feasibility of integrating GM-CSF vaccines in the postautologous BMT setting and suggest mechanisms that may contribute to the observed efficacy of immunization during the critical period of immune reconstitution [7].
  • We recently reported [Proc. Natl. Acad. Sci. USA 95 (1998) 3239] that in patients with severe depression there is a decrease in the CSF levels of 3alpha,5alpha-TH PROG, which is normalized by treatment with drugs (i.e. fluoxetine) that improve psychopathology [8].
  • The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders [9].
  • Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease [10].

High impact information on Csf2

  • Both CSF-1 and GM-CSF are responsible for transition of cells of the M phi lineage from bone marrow to blood, and from blood to tissues, and have a critical extramedullary role [11].
  • These data define a specific role for neurofibromin in negatively regulating GM-CSF signaling through Ras in haematopoietic cells and they suggest that hypersensitivity to GM-CSF may be a primary event in the development of JCML [12].
  • Single FDC-Pmix cells infected with retroviral vectors expressing GM-CSF are induced to differentiate into granulocytes and macrophages [13].
  • Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation [13].
  • Factor switching experiments have shown that both multi-CSF and GM-CSF act dominantly and in a factor concentration dependent manner to suppress c-fms expression [14].

Chemical compound and disease context of Csf2

  • The mice receiving the AAV/IL-10 virus had significantly lower levels of atherogenesis (Sudan IV-staining and histology) than the untreated or the AAV/GM-CSF-treated animals, dropping from 53% to 17% (p < 0.05) [15].
  • These results indicate that the combination use of IL-3 and GM-CSF in vivo is only a partially effective growth factor/cytokine treatment to ameliorate the hematopoietic toxicity associated with the use of the anti-viral drug zidovudine [16].
  • In this study, we show that, in contrast to the response to the commonly used i.p. irritant, thioglycolate medium, an Ag-specific methylated BSA-induced peritonitis in GM-CSF(-/-) mice was severely compromised [17].
  • Finally, to test the in vivo relevance of our findings, we showed that GM-CSF restored the survival of dexamethasone- or cyclosporine A-immunosuppressed mice from an otherwise lethal infection with Salmonella typhimurium [18].
  • To understand the mechanism involved in the exacerbation of psoriasis by lithium salts, the IL-1, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in murine skin injected with TNF in combination with LiCl were studied [19].

Biological context of Csf2


Anatomical context of Csf2


Associations of Csf2 with chemical compounds

  • In contrast to mitogen-activated Rel-/- T cells, lipopolysaccharide-stimulated Rel-/- macrophages produce higher than normal levels of GM-CSF [28].
  • In contrast, injection of a polyethylene glycol-modified form of granulocyte/macrophage colony-stimulating factor (GM-CSF) into mice only expands the myeloid-related DC subset [29].
  • The cell permeable antioxidant pyrrolidine dithiocarbamate (PDTC) decreased the intracellular levels of ROS and inhibited tyrosine phosphorylation induced by GM-CSF in MO7e cells, suggesting that ROS generation plays an important role in GM-CSF signaling [30].
  • In summary, mature hematopoietic cells with a null mutation of the betac receptor were unable to perform GM-CSF-mediated hematopoietic cell functions including glucose transport, but responded normally to a range of other ligands [31].
  • The induction of IL-5 mRNA by phorbol 12-myristate 13-acetate (PMA) stimulation was found to be cyclosporin A-resistant, in contrast to the induction of IL-2 and GM-CSF mRNAs [32].

Physical interactions of Csf2


Enzymatic interactions of Csf2


Regulatory relationships of Csf2

  • Human JMML and murine Nf1-deficient cells are hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) in methylcellulose cultures [39].
  • The work provides evidence that IL-18 is expressed by osteoblasts and inhibits OCL formation via GM-CSF production and not via IFN-gamma production [40].
  • These results have led us to propose a model for HGF synergy whereby one mechanism of action the investigated synergistic cytokines might be the ability to induce increased expression of CSF receptors [41].
  • In the present study, we show that IL-4 inhibits the production of GM-CSF in the IL-1 alpha-stimulated murine B-cell line M12.4 [42].
  • To determine the mechanism(s) by which interleukin-1 (IL-1) promotes granulopoiesis in vivo, we examined the effect of in vivo administration of IL-1 alpha on colony-stimulating factor (CSF) receptor expression on bone marrow cells (BMCs) and whether this directly correlated with progenitor cell responsiveness [43].

Other interactions of Csf2

  • The initial proliferation of these cells can also be stimulated by two other glycoproteins, granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF), although continued proliferation and differentiation requires the subsequent presence of multi-CSF [25].
  • The transcription of other cytokines including IL-13, GM-CSF, and TNF alpha was also affected, though to a lesser degree [44].
  • Neither IL-2, IL-4, GM-CSF, nor endotoxin had any significant mast cell chemotactic activity [45].
  • However examination of the subchromosomal region containing all three loci by pulsed field gel analysis showed that SPARC is at least 400-500 kb distant from the region containing the two CSF genes [46].
  • Expression of the GM-CSF gene in EL-4 cells was detected independent of CsA, whereas CsA inhibited the expression of the IL-2 gene [47].

Analytical, diagnostic and therapeutic context of Csf2


  1. Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Largaespada, D.A., Brannan, C.I., Jenkins, N.A., Copeland, N.G. Nat. Genet. (1996) [Pubmed]
  2. Comparative effects in vivo of recombinant murine interleukin 3, natural murine colony-stimulating factor-1, and recombinant murine granulocyte-macrophage colony-stimulating factor on myelopoiesis in mice. Broxmeyer, H.E., Williams, D.E., Cooper, S., Shadduck, R.K., Gillis, S., Waheed, A., Urdal, D.L., Bicknell, D.C. J. Clin. Invest. (1987) [Pubmed]
  3. Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis. Seymour, J.F., Begley, C.G., Dirksen, U., Presneill, J.J., Nicola, N.A., Moore, P.E., Schoch, O.D., van Asperen, P., Roth, B., Burdach, S., Dunn, A.R. Blood (1998) [Pubmed]
  4. Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs: granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes. Ahlers, J.D., Dunlop, N., Alling, D.W., Nara, P.L., Berzofsky, J.A. J. Immunol. (1997) [Pubmed]
  5. Genetically resistant (Ityr) and susceptible (Itys) congenic mouse strains show similar cytokine responses following infection with Salmonella dublin. Eckmann, L., Fierer, J., Kagnoff, M.F. J. Immunol. (1996) [Pubmed]
  6. Vaccination with syngeneic, lymphoma-derived immunoglobulin idiotype combined with granulocyte/macrophage colony-stimulating factor primes mice for a protective T-cell response. Kwak, L.W., Young, H.A., Pennington, R.W., Weeks, S.D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing tumor vaccines. Borrello, I., Sotomayor, E.M., Rattis, F.M., Cooke, S.K., Gu, L., Levitsky, H.I. Blood (2000) [Pubmed]
  8. The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders. Guidotti, A., Dong, E., Matsumoto, K., Pinna, G., Rasmusson, A.M., Costa, E. Brain Res. Brain Res. Rev. (2001) [Pubmed]
  9. Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies. Minghetti, L., Greco, A., Cardone, F., Puopolo, M., Ladogana, A., Almonti, S., Cunningham, C., Perry, V.H., Pocchiari, M., Levi, G. J. Neuropathol. Exp. Neurol. (2000) [Pubmed]
  10. Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease. DeMattos, R.B., Bales, K.R., Parsadanian, M., O'Dell, M.A., Foss, E.M., Paul, S.M., Holtzman, D.M. J. Neurochem. (2002) [Pubmed]
  11. Cytokine regulation of the macrophage (M phi) system studied using the colony stimulating factor-1-deficient op/op mouse. Wiktor-Jedrzejczak, W., Gordon, S. Physiol. Rev. (1996) [Pubmed]
  12. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Bollag, G., Clapp, D.W., Shih, S., Adler, F., Zhang, Y.Y., Thompson, P., Lange, B.J., Freedman, M.H., McCormick, F., Jacks, T., Shannon, K. Nat. Genet. (1996) [Pubmed]
  13. Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation. Just, U., Stocking, C., Spooncer, E., Dexter, T.M., Ostertag, W. Cell (1991) [Pubmed]
  14. Expression of the M-CSF receptor is controlled posttranscriptionally by the dominant actions of GM-CSF or multi-CSF. Gliniak, B.C., Rohrschneider, L.R. Cell (1990) [Pubmed]
  15. Inhibition of atherogenesis in LDLR knockout mice by systemic delivery of adeno-associated virus type 2-hIL-10. Liu, Y., Li, D., Chen, J., Xie, J., Bandyopadhyay, S., Zhang, D., Nemarkommula, A.R., Liu, H., Mehta, J.L., Hermonat, P.L. Atherosclerosis (2006) [Pubmed]
  16. Effect of combination interleukin-3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) on hematopoiesis administered to retrovirus-infected immunodeficient mice receiving dose-escalation zidovudine (AZT). Gallicchio, V.S., Hughes, N.K., Tse, K.F., Ling, J., Gaines, H., Bowen, T.E., Uluitu, M. Int. J. Immunopharmacol. (1995) [Pubmed]
  17. Stimulus-dependent requirement for granulocyte-macrophage colony-stimulating factor in inflammation. Cook, A.D., Braine, E.L., Hamilton, J.A. J. Immunol. (2004) [Pubmed]
  18. GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro. Xu, J., Lucas, R., Schuchmann, M., Kühnle, S., Meergans, T., Barreiros, A.P., Lohse, A.W., Otto, G., Wendel, A. J. Immunol. (2003) [Pubmed]
  19. Synergistic induction of interleukin-6 by tumor necrosis factor and lithium chloride in mice: possible role in the triggering and exacerbation of psoriasis by lithium treatment. Beyaert, R., Schulze-Osthoff, K., Van Roy, F., Fiers, W. Eur. J. Immunol. (1992) [Pubmed]
  20. Identification of 40 genes on a 1-Mb contig around the IL-4 cytokine family gene cluster on mouse chromosome 11. Wenderfer, S.E., Slack, J.P., McCluskey, T.S., Monaco, J.J. Genomics (2000) [Pubmed]
  21. Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Schmitt, R.M., Bruyns, E., Snodgrass, H.R. Genes Dev. (1991) [Pubmed]
  22. Antiapoptotic activity of Stat5 required during terminal stages of myeloid differentiation. Kieslinger, M., Woldman, I., Moriggl, R., Hofmann, J., Marine, J.C., Ihle, J.N., Beug, H., Decker, T. Genes Dev. (2000) [Pubmed]
  23. Regulation of MHC class II gene expression in macrophages by hematopoietic colony-stimulating factors (CSF). Induction by granulocyte/macrophage CSF and inhibition by CSF-1. Willman, C.L., Stewart, C.C., Miller, V., Yi, T.L., Tomasi, T.B. J. Exp. Med. (1989) [Pubmed]
  24. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. Yamamoto, M., Yamazaki, S., Uematsu, S., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Kuwata, H., Takeuchi, O., Takeshige, K., Saitoh, T., Yamaoka, S., Yamamoto, N., Yamamoto, S., Muta, T., Takeda, K., Akira, S. Nature (2004) [Pubmed]
  25. Stimulation of multipotential, erythroid and other murine haematopoietic progenitor cells by adherent cell lines in the absence of detectable multi-CSF (IL-3). Li, C.L., Johnson, G.R. Nature (1985) [Pubmed]
  26. The pathobiology of bronchial asthma. Arm, J.P., Lee, T.H. Adv. Immunol. (1992) [Pubmed]
  27. Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines. Zhang, Y.Y., Vik, T.A., Ryder, J.W., Srour, E.F., Jacks, T., Shannon, K., Clapp, D.W. J. Exp. Med. (1998) [Pubmed]
  28. Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor. Gerondakis, S., Strasser, A., Metcalf, D., Grigoriadis, G., Scheerlinck, J.Y., Grumont, R.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  29. Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Pulendran, B., Smith, J.L., Caspary, G., Brasel, K., Pettit, D., Maraskovsky, E., Maliszewski, C.R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  30. Hematopoietic growth factors signal through the formation of reactive oxygen species. Sattler, M., Winkler, T., Verma, S., Byrne, C.H., Shrikhande, G., Salgia, R., Griffin, J.D. Blood (1999) [Pubmed]
  31. Functional analysis of mature hematopoietic cells from mice lacking the betac chain of the granulocyte-macrophage colony-stimulating factor receptor. Scott, C.L., Hughes, D.A., Cary, D., Nicola, N.A., Begley, C.G., Robb, L. Blood (1998) [Pubmed]
  32. Mechanisms regulating the mRNA levels of interleukin-5 and two other coordinately expressed lymphokines in the murine T lymphoma EL4.23. Naora, H., Young, I.G. Blood (1994) [Pubmed]
  33. Granulocyte-macrophage colony-stimulating factor induces a unique set of STAT factors in murine dendritic cells. Welte, T., Koch, F., Schuler, G., Lechner, J., Doppler, W., Heufler, C. Eur. J. Immunol. (1997) [Pubmed]
  34. Cytoplasmic domains of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor beta chain (hbetac) responsible for human GM-CSF-induced myeloid cell differentiation. Matsuguchi, T., Lilly, M.B., Kraft, A.S. J. Biol. Chem. (1998) [Pubmed]
  35. Enhanced signaling through the IL-2 receptor in CD8+ T cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+ T cells rather than promotion of cell death. Cheng, L.E., Ohlén, C., Nelson, B.H., Greenberg, P.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  36. Granulocyte macrophage colony stimulating factor (GM-CSF) activity is regulated by a GM-CSF binding molecule in Wallerian degeneration following injury to peripheral nerve axons. Mirski, R., Reichert, F., Klar, A., Rotshenker, S. J. Neuroimmunol. (2003) [Pubmed]
  37. Deacetylase activity is required for STAT5-dependent GM-CSF functional activity in macrophages and differentiation to dendritic cells. Sebastián, C., Serra, M., Yeramian, A., Serrat, N., Lloberas, J., Celada, A. J. Immunol. (2008) [Pubmed]
  38. Macrophages from motheaten and viable motheaten mutant mice show increased proliferative responses to GM-CSF: detection of potential HCP substrates in GM-CSF signal transduction. Jiao, H., Yang, W., Berrada, K., Tabrizi, M., Shultz, L., Yi, T. Exp. Hematol. (1997) [Pubmed]
  39. Nf1 and Gmcsf interact in myeloid leukemogenesis. Birnbaum, R.A., O'Marcaigh, A., Wardak, Z., Zhang, Y.Y., Dranoff, G., Jacks, T., Clapp, D.W., Shannon, K.M. Mol. Cell (2000) [Pubmed]
  40. Interleukin-18 (interferon-gamma-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-gamma to inhibit osteoclast formation. Udagawa, N., Horwood, N.J., Elliott, J., Mackay, A., Owens, J., Okamura, H., Kurimoto, M., Chambers, T.J., Martin, T.J., Gillespie, M.T. J. Exp. Med. (1997) [Pubmed]
  41. Induction of colony-stimulating factor receptor expression on hematopoietic progenitor cells: proposed mechanism for growth factor synergism. Jacobsen, S.E., Ruscetti, F.W., Dubois, C.M., Wine, J., Keller, J.R. Blood (1992) [Pubmed]
  42. Interleukin-4 inhibits interleukin-1 alpha-induced granulocyte-macrophage colony-stimulating factor gene expression in a murine B-lymphocyte cell line via downregulation of RNA precursor. Akahane, K., Pluznik, D.H. Blood (1992) [Pubmed]
  43. In vivo effect of interleukin-1 alpha on hematopoiesis: role of colony-stimulating factor receptor modulation. Hestdal, K., Jacobsen, S.E., Ruscetti, F.W., Dubois, C.M., Longo, D.L., Chizzonite, R., Oppenheim, J.J., Keller, J.R. Blood (1992) [Pubmed]
  44. Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Hodge, M.R., Ranger, A.M., Charles de la Brousse, F., Hoey, T., Grusby, M.J., Glimcher, L.H. Immunity (1996) [Pubmed]
  45. Stimulation of mast cell chemotaxis by interleukin 3. Matsuura, N., Zetter, B.R. J. Exp. Med. (1989) [Pubmed]
  46. Close genetic and physical linkage between the murine haemopoietic growth factor genes GM-CSF and Multi-CSF (IL3). Barlow, D.P., Bućan, M., Lehrach, H., Hogan, B.L., Gough, N.M. EMBO J. (1987) [Pubmed]
  47. Differential regulation of colony-stimulating factors and interleukin 2 production by cyclosporin A. Bickel, M., Tsuda, H., Amstad, P., Evequoz, V., Mergenhagen, S.E., Wahl, S.M., Pluznik, D.H. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  48. Granulocyte macrophage colony stimulating factor produced in lesioned peripheral nerves induces the up-regulation of cell surface expression of MAC-2 by macrophages and Schwann cells. Saada, A., Reichert, F., Rotshenker, S. J. Cell Biol. (1996) [Pubmed]
  49. Gene immunotherapy in murine acute myeloid leukemia: granulocyte-macrophage colony-stimulating factor tumor cell vaccines elicit more potent antitumor immunity compared with B7 family and other cytokine vaccines. Dunussi-Joannopoulos, K., Dranoff, G., Weinstein, H.J., Ferrara, J.L., Bierer, B.E., Croop, J.M. Blood (1998) [Pubmed]
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