The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CSF3  -  colony stimulating factor 3 (granulocyte)

Homo sapiens

Synonyms: C17orf33, CSF3OS, G-CSF, GCSF, Granulocyte colony-stimulating factor, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CSF3


Psychiatry related information on CSF3


High impact information on CSF3

  • In myeloid leukemia and myelodysplastic syndromes, CSF treatment, particularly G-CSF, has proved effective for certain patients in improving neutrophil, platelet, and occasionally red cell production while reducing blast cells [12].
  • BACKGROUND: In recipients of allogeneic hematopoietic-cell transplants, peripheral-blood cells mobilized with the use of filgrastim (recombinant granulocyte colony-stimulating factor) engraft more rapidly than bone marrow [13].
  • METHODS: We performed a randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor (G-CSF) in afebrile outpatients with severe chemotherapy-induced neutropenia [14].
  • The median time to an absolute neutrophil count of at least 500 per cubic millimeter was significantly shorter for patients who received G-CSF (two days, vs. four days for the patients given placebo) [14].
  • Among patients who did not have febrile neutropenia during the first week of G-CSF or placebo injections, higher systemic exposure to the growth factor on day 7 was significantly related to a lower probability of subsequent hospitalization (P=0.049) [15].

Chemical compound and disease context of CSF3


Biological context of CSF3

  • Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of hormone-like glycoproteins that regulate haematopoietic cell proliferation and differentiation, and G-CSF almost exclusively stimulates the colony formation of granulocytes from committed precursor cells in semi-solid agar culture [20].
  • GM-CSF and G-CSF both induce a change from low to high-affinity neutrophil IgA Fc crystallizable fragment receptors within 30 min; a change which is associated with the development of IgA-mediated phagocytosis [21].
  • We have now determined the partial amino-acid sequence of the purified G-CSF protein, and by using oligonucleotides as probes, have isolated several clones containing G-CSF complementary DNA from the cDNA library prepared with messenger RNA from CHU-2 cells [20].
  • The complete nucleotide sequences of two of these cDNAs were determined and the expression of the cDNA in monkey COS cells gave rise to a protein showing authentic G-CSF activity [20].
  • Furthermore, Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G-CSF gene in CHU-2 cells [20].

Anatomical context of CSF3

  • The haematopoietic factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) prime neutrophils to be more responsive to a variety of stimuli [21].
  • We now report that treatment of endothelial cells (EC) with modified low-density lipoproteins obtained by mild iron oxidation or by prolonged storage, results in a rapid and large induction of the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage CSF (M-CSF) and granulocyte CSF (G-CSF) [22].
  • These growth factors affect the differentiation, survival, proliferation, migration and metabolism of macrophages/granulocytes, and G-CSF and GM-CSF also affect the migration and proliferation of EC [22].
  • Transcripts of the G-CSF, IL-1 alpha, and IL-1 beta genes were never detected in NK cells in these experiments [23].
  • Whereas a mixture of G-CSF, M-CSF, and IL 3 produced a mitogenic response in the prostatic carcinoma cells, these three factors were not present in our bone marrow samples in sufficient quantities to promote the observed proliferative response [24].

Associations of CSF3 with chemical compounds

  • The purified recombinant G-CSF runs as a single band with an apparent Mr of 19,000 on a polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate [25].
  • Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA [26].
  • Although the G-CSFR belongs to the cytokine receptor superfamily, which lacks an intracellular kinase domain, G-CSF-induced tyrosine phosphorylation of cellular proteins is critical for its biologic activities [27].
  • Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates proliferation and differentiation of progenitor cells of neutrophils by signaling through its receptor (G-CSFR) [27].
  • The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone [26].
  • We demonstrate that slanDCs (14.9 x 10(6)/L to 64.0 x 10(6)/L) are efficiently mobilized by G-CSF and retain their capacity to produce IL-12 and TNF-alpha at high levels [28].

Physical interactions of CSF3

  • Similarly, 125I-IL-8 ligand binding to PMN is increased by G-CSF and decreased by LPS treatment [29].
  • Analysis of the electrostatic potentials supports a recently proposed hetero-oligomeric model for a high-affinity IL-4 receptor and suggests a possible new receptor binding mode for G-CSF; it also provides valuable information for guiding structural and mutagenesis studies of signal-transducing proteins and their receptors [30].
  • A chimeric cytokine, myelopoietin-1, composed of daniplestim and a G-CSF receptor agonist binds both the IL-3 and G-CSF receptors [31].
  • The tax response of the G-CSF promoter requires not only the conserved CK-1 sequence but also an adjacent NF-IL6 binding site that may explain the cell restricted function of the G-CSF promoter [32].
  • Our cell-level model suggests that ligand depletion may be reduced in vitro by decreasing the endosomal affinity of endocytosed GCSF/GCSFR complexes, matching experimental findings [33].

Enzymatic interactions of CSF3


Regulatory relationships of CSF3

  • The proliferative effects of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) on human hematopoietic cells have been reported, but the intranuclear mechanism of early signal response to these mitogenic stimuli remains unknown [3].
  • Thus, these results indicate that one mechanism of the pathogenesis in SCN patients is reduced responsiveness of neutrophil progenitor cells to G-CSF and that SCF can enhance the responsiveness of these cells to G-CSF [37].
  • On the other hand, in six cases, G-CSF enhanced the IL-3- or GM-CSF-stimulated thymidine uptake [38].
  • Tumor necrosis factor alpha (TNF alpha) stimulates production of granulocyte colony-stimulating factor (G-CSF) protein and mRNA in fibroblast cells [39].
  • In other words, IL-4 may induce progenitor cells to become sensitive to G-CSF and thereby induce neutrophil differentiation [40].

Other interactions of CSF3

  • Together these data add to our understanding of the mechanisms of cytokine receptor signaling, emphasize the role of GCSFR mutations in the etiology of SCN, and implicate such mutations in G-CSF hyporesponsiveness [2].
  • G-CSF receptor numbers on purified blood granulocytes are also downmodulated by TNF [41].
  • In parallel with regrowth from the G0/G1 resting state by addition of recombinant human G-CSF or M-CSF after serum deprivation, NKM-1 cells showed the transient expression of the junB gene with a peak of ninefold above the basal level between 40 and 60 min [3].
  • However, pretreatment of patients with G-CSF with or without SCF did not enhance the retroviral infectability of growth factor-mobilized progenitor cells [42].
  • When 32D cells are switched to medium containing granulocyte colony-stimulating factor (G-CSF) instead of IL-3, D-type cyclins are degraded and, in the absence of their associated kinase activity, the cells arrest in the first gap phase (G1) of the cell cycle and differentiate to neutrophils [43].

Analytical, diagnostic and therapeutic context of CSF3


  1. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Souza, L.M., Boone, T.C., Gabrilove, J., Lai, P.H., Zsebo, K.M., Murdock, D.C., Chazin, V.R., Bruszewski, J., Lu, H., Chen, K.K. Science (1986) [Pubmed]
  2. Novel point mutation in the extracellular domain of the granulocyte colony-stimulating factor (G-CSF) receptor in a case of severe congenital neutropenia hyporesponsive to G-CSF treatment. Ward, A.C., van Aesch, Y.M., Gits, J., Schelen, A.M., de Koning, J.P., van Leeuwen, D., Freedman, M.H., Touw, I.P. J. Exp. Med. (1999) [Pubmed]
  3. Induction of junB expression, but not c-jun, by granulocyte colony-stimulating factor or macrophage colony-stimulating factor in the proliferative response of human myeloid leukemia cells. Adachi, K., Saito, H. J. Clin. Invest. (1992) [Pubmed]
  4. The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor. Nagata, S., Tsuchiya, M., Asano, S., Yamamoto, O., Hirata, Y., Kubota, N., Oheda, M., Nomura, H., Yamazaki, T. EMBO J. (1986) [Pubmed]
  5. Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection. Xiao, B.G., Lu, C.Z., Link, H. J. Cell. Mol. Med. (2007) [Pubmed]
  6. Novel strategies for granulocyte colony-stimulating factor treatment of severe prolonged neutropenia suggested by mathematical modeling. Shochat, E., Rom-Kedar, V. Clin. Cancer Res. (2008) [Pubmed]
  7. Endotoxin down-modulates granulocyte colony-stimulating factor receptor (CD114) on human neutrophils. Hollenstein, U., Homoncik, M., Stohlawetz, P.J., Marsik, C., Sieder, A., Eichler, H.G., Jilma, B. J. Infect. Dis. (2000) [Pubmed]
  8. A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia. Lalami, Y., Paesmans, M., Aoun, M., Munoz-Bermeo, R., Reuss, K., Cherifi, S., Alexopoulos, C.G., Klastersky, J. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. (2004) [Pubmed]
  9. Identification and characterization of receptors for granulocyte colony-stimulating factor on human placenta and trophoblastic cells. Uzumaki, H., Okabe, T., Sasaki, N., Hagiwara, K., Takaku, F., Tobita, M., Yasukawa, K., Ito, S., Umezawa, Y. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  10. G-CSF plasma levels in clozapine-induced neutropenia. Jauss, M., Pantel, J., Werle, E., Schröder, J. Biol. Psychiatry (2000) [Pubmed]
  11. Phase I study of mitozantrone, methotrexate and mitomycin with granulocyte colony-stimulating factor (filgrastim) in patients with advanced breast cancer. O'Brien, M.E., Nicolson, M., Montes, A., Tidy, A., Ashley, S., Powles, T.J. Br. J. Cancer (1994) [Pubmed]
  12. The clinical use of colony stimulating factors. Moore, M.A. Annu. Rev. Immunol. (1991) [Pubmed]
  13. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. Bensinger, W.I., Martin, P.J., Storer, B., Clift, R., Forman, S.J., Negrin, R., Kashyap, A., Flowers, M.E., Lilleby, K., Chauncey, T.R., Storb, R., Appelbaum, F.R. N. Engl. J. Med. (2001) [Pubmed]
  14. Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia. Hartmann, L.C., Tschetter, L.K., Habermann, T.M., Ebbert, L.P., Johnson, P.S., Mailliard, J.A., Levitt, R., Suman, V.J., Witzig, T.E., Wieand, H.S., Miller, L.L., Moertel, C.G. N. Engl. J. Med. (1997) [Pubmed]
  15. Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia. Pui, C.H., Boyett, J.M., Hughes, W.T., Rivera, G.K., Hancock, M.L., Sandlund, J.T., Synold, T., Relling, M.V., Ribeiro, R.C., Crist, W.M., Evans, W.E. N. Engl. J. Med. (1997) [Pubmed]
  16. Binding of G-CSF, GM-CSF, tumor necrosis factor-alpha, and gamma-interferon to cell surface receptors on human myeloid leukemia cells triggers rapid tyrosine and serine phosphorylation of a 75-Kd protein. Evans, J.P., Mire-Sluis, A.R., Hoffbrand, A.V., Wickremasinghe, R.G. Blood (1990) [Pubmed]
  17. Kinetics and mechanisms of recombinant human granulocyte-colony stimulating factor-induced neutrophilia. Ulich, T.R., del Castillo, J., Souza, L. Am. J. Pathol. (1988) [Pubmed]
  18. The role of myelopoietic growth factors in managing cancer in the elderly. Balducci, L., Carreca, I. Drugs (2002) [Pubmed]
  19. Lenograstim. A review of its pharmacological properties and therapeutic efficacy in neutropenia and related clinical settings. Frampton, J.E., Yarker, Y.E., Goa, K.L. Drugs (1995) [Pubmed]
  20. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nagata, S., Tsuchiya, M., Asano, S., Kaziro, Y., Yamazaki, T., Yamamoto, O., Hirata, Y., Kubota, N., Oheda, M., Nomura, H. Nature (1986) [Pubmed]
  21. GM-CSF induces human neutrophil IgA-mediated phagocytosis by an IgA Fc receptor activation mechanism. Weisbart, R.H., Kacena, A., Schuh, A., Golde, D.W. Nature (1988) [Pubmed]
  22. Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Rajavashisth, T.B., Andalibi, A., Territo, M.C., Berliner, J.A., Navab, M., Fogelman, A.M., Lusis, A.J. Nature (1990) [Pubmed]
  23. 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]
  24. Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. Chackal-Roy, M., Niemeyer, C., Moore, M., Zetter, B.R. J. Clin. Invest. (1989) [Pubmed]
  25. Characterization of recombinant human granulocyte-colony-stimulating factor produced in mouse cells. Tsuchiya, M., Nomura, H., Asano, S., Kaziro, Y., Nagata, S. EMBO J. (1987) [Pubmed]
  26. Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro. Demetri, G.D., Zenzie, B.W., Rheinwald, J.G., Griffin, J.D. Blood (1989) [Pubmed]
  27. Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Tian, S.S., Lamb, P., Seidel, H.M., Stein, R.B., Rosen, J. Blood (1994) [Pubmed]
  28. G-CSF mobilizes slanDCs (6-sulfo LacNAc+ dendritic cells) with a high proinflammatory capacity. Baumeister, S.H., Hölig, K., Bornhäuser, M., Meurer, M., Rieber, E.P., Schäkel, K. Blood (2007) [Pubmed]
  29. Granulocyte-colony stimulating factor and lipopolysaccharide regulate the expression of interleukin 8 receptors on polymorphonuclear leukocytes. Lloyd, A.R., Biragyn, A., Johnston, J.A., Taub, D.D., Xu, L., Michiel, D., Sprenger, H., Oppenheim, J.J., Kelvin, D.J. J. Biol. Chem. (1995) [Pubmed]
  30. Receptor binding properties of four-helix-bundle growth factors deduced from electrostatic analysis. Demchuk, E., Mueller, T., Oschkinat, H., Sebald, W., Wade, R.C. Protein Sci. (1994) [Pubmed]
  31. Enhanced ability of daniplestim and myelopoietin-1 to suppress apoptosis in human hematopoietic cells. McCubrey, J.A., Blalock, W.L., Saleh, O., Pearce, M., Burrows, C., Steelman, L.S., Lee, J.T., Franklin, R.A., Oberhaus, S.M., Moye, P.W., Doshi, P.D., McKearn, J.P. Leukemia (2001) [Pubmed]
  32. HTLV-1 tax activation of the GM-CSF and G-CSF promoters requires the interaction of NF-kB with other transcription factor families. Himes, S.R., Coles, L.S., Katsikeros, R., Lang, R.K., Shannon, M.F. Oncogene (1993) [Pubmed]
  33. Cell-level pharmacokinetic model of granulocyte colony-stimulating factor: implications for ligand lifetime and potency in vivo. Sarkar, C.A., Lauffenburger, D.A. Mol. Pharmacol. (2003) [Pubmed]
  34. The role of STAT3 in granulocyte colony-stimulating factor-induced enhancement of neutrophilic differentiation of Me2SO-treated HL-60 cells. GM-CSF inhibits the nuclear translocation of tyrosine-phosphorylated STAT3. Yamaguchi, T., Mukasa, T., Uchida, E., Kanayasu-Toyoda, T., Hayakawa, T. J. Biol. Chem. (1999) [Pubmed]
  35. Commitment of neutrophilic differentiation and proliferation of HL-60 cells coincides with expression of transferrin receptor. Effect of granulocyte colony stimulating factor on differentiation and proliferation. Kanayasu-Toyoda, T., Yamaguchi, T., Uchida, E., Hayakawa, T. J. Biol. Chem. (1999) [Pubmed]
  36. Induction of megakaryocytes to synthesize and store a releasable pool of human factor VIII. Wilcox, D.A., Shi, Q., Nurden, P., Haberichter, S.L., Rosenberg, J.B., Johnson, B.D., Nurden, A.T., White, G.C., Montgomery, R.R. J. Thromb. Haemost. (2003) [Pubmed]
  37. Severe congenital neutropenia: abnormal growth and differentiation of myeloid progenitors to granulocyte colony-stimulating factor (G-CSF) but normal response to G-CSF plus stem cell factor. Hestdal, K., Welte, K., Lie, S.O., Keller, J.R., Ruscetti, F.W., Abrahamsen, T.G. Blood (1993) [Pubmed]
  38. Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system. Delwel, R., Salem, M., Pellens, C., Dorssers, L., Wagemaker, G., Clark, S., Löwenberg, B. Blood (1988) [Pubmed]
  39. Recombinant human TNF alpha stimulates production of granulocyte colony-stimulating factor. Koeffler, H.P., Gasson, J., Ranyard, J., Souza, L., Shepard, M., Munker, R. Blood (1987) [Pubmed]
  40. Actions of human interleukin-4/B-cell stimulatory factor-1 on proliferation and differentiation of enriched hematopoietic progenitor cells in culture. Sonoda, Y., Okuda, T., Yokota, S., Maekawa, T., Shizumi, Y., Nishigaki, H., Misawa, S., Fujii, H., Abe, T. Blood (1990) [Pubmed]
  41. Tumor necrosis factor downregulates granulocyte-colony-stimulating factor receptor expression on human acute myeloid leukemia cells and granulocytes. Elbaz, O., Budel, L.M., Hoogerbrugge, H., Touw, I.P., Delwel, R., Mahmoud, L.A., Löwenberg, B. J. Clin. Invest. (1991) [Pubmed]
  42. Retroviral transduction of human progenitor cells: use of granulocyte colony-stimulating factor plus stem cell factor to mobilize progenitor cells in vivo and stimulation by Flt3/Flk-2 ligand in vitro. Elwood, N.J., Zogos, H., Willson, T., Begley, C.G. Blood (1996) [Pubmed]
  43. Features of macrophage differentiation induced by p19INK4d, a specific inhibitor of cyclin D-dependent kinases. Adachi, M., Roussel, M.F., Havenith, K., Sherr, C.J. Blood (1997) [Pubmed]
  44. Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin-1 beta (IL-1 beta), IL-6, IL-3, interferon-gamma, and erythropoietin. Brugger, W., Möcklin, W., Heimfeld, S., Berenson, R.J., Mertelsmann, R., Kanz, L. Blood (1993) [Pubmed]
  45. G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases. Franzke, A., Piao, W., Lauber, J., Gatzlaff, P., Könecke, C., Hansen, W., Schmitt-Thomsen, A., Hertenstein, B., Buer, J., Ganser, A. Blood (2003) [Pubmed]
  46. Cycling status of CD34+ cells mobilized into peripheral blood of healthy donors by recombinant human granulocyte colony-stimulating factor. Lemoli, R.M., Tafuri, A., Fortuna, A., Petrucci, M.T., Ricciardi, M.R., Catani, L., Rondelli, D., Fogli, M., Leopardi, G., Ariola, C., Tura, S. Blood (1997) [Pubmed]
  47. Endogenous interleukin-8 (IL-8) surge in granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization. Watanabe, T., Kawano, Y., Kanamaru, S., Onishi, T., Kaneko, S., Wakata, Y., Nakagawa, R., Makimoto, A., Kuroda, Y., Takaue, Y., Talmadge, J.E. Blood (1999) [Pubmed]
WikiGenes - Universities