Skip to main content

Advertisement

Log in

Granulocyte–macrophage colony-stimulating factor: not just another haematopoietic growth factor

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Granulocyte–macrophage colony-stimulating factor (GM-CSF) is often used to treat leucopenia. Other haematopoietins may increase the number of circulating leucocytes with higher efficiency, but GM-CSF has additional effects that may be far more relevant than its haematopoietic activity. GM-CSF induces differentiation, proliferation and activation of macrophages and dendritic cells which are necessary for the subsequent T helper cell type 1 and cytotoxic T lymphocyte activation. GM-CSF haematopoietic and non-haematopoietic functions have pro-inflammatory and immune regulatory potential to treat a variety of autoimmune diseases and tumours. On the other hand, GM-CSF deficiency leads to various immune dysfunctions and the current utilization of GM-CSF as haematopoietic factor might be an accurate but very incomplete indication for a cytokine with vast clinical potential.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

AML:

Acute myeloid leukaemia

AMØ:

Alveolar macrophage

BM:

Bone marrow

CISH:

Cytokine inducible SH2-domain

DC:

Dendritic cell

GRAP:

GM-CSFRα subunit-associated protein

iNKT:

Invariant natural killer T

IκK:

IκB kinase

MØ:

Macrophage

MAPK:

Mitogen-activated kinase-like protein

NFκB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

IkB:

Nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor β

PI3K:

Phosphatidylinositol 3 kinase

PKC:

Protein kinase C

PAP:

Pulmonary alveolar proteinosis

rhGM-CSF:

Recombinant human GM-CSF

rhG-CSF:

Recombinant human granulocyte colony-stimulating factor

STAT:

Signal transducers and activators of transcription

SLAP:

SRC-like adapter protein

TLR:

Toll-like receptor

References

  1. Metcalf D. Hematopoietic cytokines. Blood. 2008;111:485–91.

    CAS  PubMed  Google Scholar 

  2. Bradley TR, Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966;44:287–99.

    CAS  PubMed  Google Scholar 

  3. Sheridan JW, Metcalf D. A low molecular weight factor in lung-conditioned medium stimulating granulocyte and monocyte colony formation in vitro. J Cell Physiol. 1973;81:11–23.

    CAS  PubMed  Google Scholar 

  4. Burgess AW, Camakaris J, Metcalf D. Purification and properties of colony-stimulating factor from mouse lung–conditioned medium. J Biol Chem. 1977;252:1998–2003.

    CAS  PubMed  Google Scholar 

  5. Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008;8:533–44.

    CAS  PubMed  Google Scholar 

  6. Lane TA, Law P, Maruyama M, et al. Harvesting and enrichment of hematopoietic progenitor cells mobilized into the peripheral blood of normal donors by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF: potential role in allogeneic marrow transplantation. Blood. 1995;85:275–82.

    CAS  PubMed  Google Scholar 

  7. Armitage JO. Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1998;92:4491–508.

    CAS  PubMed  Google Scholar 

  8. Conti L, Gessani S. GM-CSF in the generation of dendritic cells from human blood monocyte precursors: recent advances. Immunobiology. 2008;213:859–70.

    CAS  PubMed  Google Scholar 

  9. Fukuzawa H, Sawada M, Kayahara T, et al. Identification of GM-CSF in Paneth cells using single-cell RT-PCR. Biochem Biophys Res Commun. 2003;312:897–902.

    CAS  PubMed  Google Scholar 

  10. Hamilton JA, Anderson GP. GM-CSF biology. Growth Factors. 2004;22:225–31.

    CAS  PubMed  Google Scholar 

  11. Xing Z, Braciak T, Ohkawara Y, et al. Gene transfer for cytokine functional studies in the lung: the multifunctional role of GM-CSF in pulmonary inflammation. J Leukoc Biol. 1996;59:481–8.

    CAS  PubMed  Google Scholar 

  12. de Groot RP, Coffer PJ, Koenderman L. Regulation of proliferation, differentiation and survival by the IL-3/IL-5/GM-CSF receptor family. Cell Signal. 1998;10:619–28.

    PubMed  Google Scholar 

  13. Hansen G, Hercus TR, McClure BJ, et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell. 2008;134:496–507.

    CAS  PubMed  Google Scholar 

  14. Matsuguchi T, Zhao Y, Lilly M, et al. The cytoplasmic domain of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor subunit is essential for both GM-CSF-mediated growth and differentiation. J Biol Chem. 1997;272:17450–9.

    CAS  PubMed  Google Scholar 

  15. McClure BJ, Hercus TR, Cambareri BA, et al. Molecular assembly of the ternary granulocyte-macrophage colony-stimulating factor receptor complex. Blood. 2003;101:1308–15.

    CAS  PubMed  Google Scholar 

  16. Sawada M, Itoh Y, Suzumura A, et al. Expression of cytokine receptors in cultured neuronal and glial cells. Neurosci Lett. 1993;160:131–4.

    CAS  PubMed  Google Scholar 

  17. Carr PD, Gustin SE, Church AP, et al. Structure of the complete extracellular domain of the common subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration. Cell. 2001;104:291–300.

    CAS  PubMed  Google Scholar 

  18. McClure BJ, Hercus TR, Cambareri BA, et al. Molecular assembly of the ternary granulocyte-macrophage colony-stimulating factor receptor complex. Blood. 2003;101:1308–15.

    CAS  PubMed  Google Scholar 

  19. Hansen G, Hercus TR, Xu Y, et al. Crystallization and preliminary X-ray diffraction analysis of the ternary human GM-CSF receptor complex. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008;64:711–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Choi JK, Kim KH, Park H, et al. Granulocyte macrophage-colony stimulating factor shows anti-apoptotic activity in neural progenitor cells via JAK/STAT5-Bcl-2 pathway. Apoptosis. 2011;16:127–34.

    CAS  PubMed  Google Scholar 

  21. O’Mahony DS, Pham U, Iyer R, et al. Differential constitutive and cytokine-modulated expression of human Toll-like receptors in primary neutrophils, monocytes, and macrophages. Int J Med Sci. 2008;5:1–8.

    PubMed Central  PubMed  Google Scholar 

  22. Tanimoto A, Murata Y, Wang KY, et al. Monocyte chemoattractant protein-1 expression is enhanced by granulocyte-macrophage colony-stimulating factor via Jak2-Stat5 signalling and inhibited by atorvastatin in human monocytic U937 cells. J Biol Chem. 2008;283:4643–51.

    CAS  PubMed  Google Scholar 

  23. Liontos LM, Dissanayake D, Ohashi PS, et al. The Src-like adaptor protein regulates GM-CSFR signalling and monocytic dendritic cell maturation. J Immunol. 2011;186:1923–33.

    CAS  PubMed  Google Scholar 

  24. Domen J, Weissman IL. Hematopoietic stem cells need two signals to prevent apoptosis; BCL-2 can provide one of these, Kitl/c-Kit signalling the other. J Exp Med. 2000;192:1707–18.

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Chen J, Cárcamo JM, Golde DW. The alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor interacts with c-Kit and inhibits c-Kit signalling. J Biol Chem. 2006;281:22421–6.

    CAS  PubMed  Google Scholar 

  26. Lilly MB, Zemskova M, Frankel AE, et al. Distinct domains of the human granulocyte-macrophage colony-stimulating factor receptor alpha subunit mediate activation of Jak/Stat signalling and differentiation. Blood. 2001;97:1662–70.

    CAS  PubMed  Google Scholar 

  27. Crosier KE, Wong GG, Mathey-Prevot B, et al. A functional isoform of the human granulocyte/macrophage colony-stimulating factor receptor has an unusual cytoplasmic domain. Proc Natl Acad Sci USA. 1991;88:7744–8.

    CAS  PubMed  Google Scholar 

  28. Raines MA, Liu L, Quan SG, et al. Identification and molecular cloning of a soluble human granulocyte-macrophage colony-stimulating factor receptor. Proc Natl Acad Sci USA. 1991;88:8203–7.

    CAS  PubMed  Google Scholar 

  29. Leukine® Prescribing information. Available at http://products.sanofi.us/Leukine/Leukine.html Accessed on September 2013.

  30. Jiang D, Schwarz H. Regulation of granulocyte and macrophage populations of murine bone marrow cells by G-CSF and CD137 protein. PLoS One. 2010;5:e15565.

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Crawford J, Armitage J, Balducci L, et al. Myeloid growth factors. J Natl Compr Canc Netw. 2009;7:64–83.

    CAS  PubMed  Google Scholar 

  32. Kelsen JR, Rosh J, Heyman M, et al. Phase I trial of sargramostim in pediatric Crohn’s disease. Inflamm Bowel Dis. 2010;16:1203–8.

    PubMed  Google Scholar 

  33. The FDA Safety Information and Adverse Event Reporting Program, 2008. Leukine safety information Available at http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm090918.htm, Accessed on October 2013.

  34. Martinez-Moczygemba M, Doan ML, Elidemir O, et al. Pulmonary alveolar proteinosis caused by deletion of the GM-CSFR{alpha} gene in the X chromosome pseudoautosomal region 1. J Exp Med. 2008;205:2711–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Hamilton JA, Whitty GA, Stanton H, et al. Effects of macrophage-colony stimulating factor on human monocytes: induction of expression of urokinase-type plasminogen activator, but not of secreted prostaglandin E2, interleukin-6, interleukin-1, or tumour necrosis factor-alpha. J Leukoc Biol. 1993;53:707–14.

    CAS  PubMed  Google Scholar 

  36. Takahashi GW, Andrews DF 3rd, Lilly MB, et al. Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes. Blood. 1993;81:357–64.

    CAS  PubMed  Google Scholar 

  37. Selgas R, Fernández de Castro M, Jiménez C, Selgas R, et al. Immunomodulation of peritoneal macrophages by granulocyte-macrophage colony-stimulating factor in humans. Kidney Int. 1996;50:2070–8.

    CAS  PubMed  Google Scholar 

  38. Hart PH, Whitty GA, Piccoli DS, et al. Synergistic activation of human monocytes by granulocyte-macrophage colony-stimulating factor and IFN-gamma. Increased TNF-alpha but not IL-1 activity. J Immunol. 1988;141:1516–21.

    CAS  PubMed  Google Scholar 

  39. Hazenberg BP, Van Leeuwen MA, Van Rijswijk MH, et al. Correction of granulocytopenia in Felty’s syndrome by granulocyte-macrophage colony-stimulating factor. Simultaneous induction of interleukin-6 release and flare-up of the arthritis. Blood. 1989;74:2769–70.

    CAS  PubMed  Google Scholar 

  40. de Vries EG, Willemse PH, Biesma B, et al. Flare-up of rheumatoid arthritis during GM-CSF treatment after chemotherapy. Lancet. 1991;338:517–8.

    PubMed  Google Scholar 

  41. Bischof RJ, Zafiropoulos D, Hamilton JA, et al. Exacerbation of acute inflammatory arthritis by the colony-stimulating factors CSF-1 and granulocyte macrophage (GM)-CSF: evidence of macrophage infiltration and local proliferation. Clin Exp Immunol. 2000;119:361–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Campbell IK, Bendele A, Smith DA, et al. Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice. Ann Rheum Dis. 1997;56:364–8.

    CAS  PubMed  Google Scholar 

  43. Burmester GR, Weinblatt ME, McInnes IB, et al. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis. 2013;72:1445–52.

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Mudzinski SP, Christian TP, Guo TL, et al. Expression of HLA-DR (major histocompatibility complex class II) on neutrophils from patients treated with granulocyte-macrophage colony-stimulating factor for mobilization of stem cells. Blood. 1995;86:2452–3.

    CAS  PubMed  Google Scholar 

  45. Fanger NA, Liu C, Guyre PM, et al. Activation of human T cells by major histocompatibility complex class II expressing neutrophils: proliferation in the presence of superantigen, but not tetanus toxoid. Blood. 1997;89:4128–35.

    CAS  PubMed  Google Scholar 

  46. Herold S, Mayer K, Lohmeyer J. Acute lung injury. How macrophages orchestrate resolution of inflammation and tissue repair. Front Immunol. 2001;2:6.

    Google Scholar 

  47. Cakarova L, Marsh LM, Wilhelm J, et al. Macrophage tumor necrosis factor-alpha induces epithelial expression of granulocyte-macrophage colony-stimulating factor: impact on alveolar epithelial repair. Am J Respir Crit Care Med. 2009;180:521–32.

    CAS  PubMed  Google Scholar 

  48. Krausgruber T, Blazek K, Smallie T, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011;12:231–8.

    CAS  PubMed  Google Scholar 

  49. Miah MA, Yoon CH, Kim J, et al. CISH is induced during DC development and regulates DC-mediated CTL activation. Eur J Immunol. 2012;42:58–68.

    CAS  PubMed  Google Scholar 

  50. Hornell TM, Beresford GW, Bushey A, et al. Regulation of the class II MHC pathway in primary human monocytes by granulocyte-macrophage colony-stimulating factor. J Immunol. 2003;171:2374–83.

    CAS  PubMed  Google Scholar 

  51. McCormick S, Santosuosso M, Zhang XZ, et al. Manipulation of dendritic cells for host defence against intracellular infections. Biochem Soc Trans. 2006;34:283–6.

    CAS  PubMed  Google Scholar 

  52. Moldenhauer LM, Keenihan SN, Hayball JD, et al. GM-CSF is an essential regulator of T cell activation competence in uterine dendritic cells during early pregnancy in mice. J Immunol. 2010;185:7085–96.

    CAS  PubMed  Google Scholar 

  53. Hesske L, Vincenzetti C, Heikenwalder M, et al. Induction of inhibitory central nervous system-derived and stimulatory blood-derived dendritic cells suggests a dual role for granulocyte-macrophage colony-stimulating factor in central nervous system inflammation. Brain. 2010;133(Pt 6):1637–54.

    PubMed  Google Scholar 

  54. Sonderegger I, Iezzi G, Maier R, et al. GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival. J Exp Med. 2008;205:2281–94.

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Biondo M, Nasa Z, Marshall A, Toh BH, Alderuccio F. Local transgenic expression of granulocyte macrophage-colony stimulating factor initiates autoimmunity. J Immunol. 2001;166(3):2090–9.

    CAS  PubMed  Google Scholar 

  56. Kim DH, Sandoval D, Reed J, et al. The role of GM-CSF in adipose tissue inflammation. Am J Physiol Endocrinol Metab. 2008;295:E1038–46.

    CAS  PubMed  Google Scholar 

  57. Exley MA, Koziel MJ. To be or not to be NKT: natural killer T cells in the liver. Hepatology. 2004;40:1033–40.

    PubMed  Google Scholar 

  58. Brochériou I, Maouche S, Durand H, et al. Antagonistic regulation of macrophage phenotype by M-CSF and GM-CSF: implication in atherosclerosis. Atherosclerosis. 2011;214:316–24.

    PubMed  Google Scholar 

  59. Saitoh T, Kishida H, Tsukada Y, et al. Clinical significance of increased plasma concentration of macrophage colony-stimulating factor in patients with angina pectoris. J Am Coll Cardiol. 2000;35:655–65.

    CAS  PubMed  Google Scholar 

  60. Oren H, Erbay AR, Balci M, et al. Role of novel biomarkers of inflammation in patients with stable coronary heart disease. Angiology. 2007;58:148–55.

    CAS  PubMed  Google Scholar 

  61. Kellar RS, Lancaster JJ, Thai HM, et al. Antibody to granulocyte-macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function following myocardial infarction in a rat coronary-artery ligation model. J Cardiovasc Pharmacol. 2011;57:568–74.

    CAS  PubMed  Google Scholar 

  62. Sugiyama Y, Yagita Y, Oyama N, et al. Granulocyte colony-stimulating factor enhances arteriogenesis and ameliorates cerebral damage in a mouse model of ischemic stroke. Stroke. 2011;42:770–5.

    CAS  PubMed  Google Scholar 

  63. Tu J, Karasavvas N, Heaney ML, et al. Molecular characterization of a granulocyte macrophage-colony-stimulating factor receptor alpha subunit-associated protein. GRAP Blood. 2000;96:794–9.

    CAS  Google Scholar 

  64. Stösser S, Schweizerhof M, Kuner R. Hematopoietic colony-stimulating factors: new players in tumor-nerve interactions. J Mol Med. 2011;89:321–9.

    PubMed Central  PubMed  Google Scholar 

  65. Ding DX, Rivas CI, Heaney ML, et al. The alpha subunit of the human granulocyte-macrophage colony-stimulating factor receptor signals for glucose transport via a phosphorylation-independent pathway. Proc Natl Acad Sci USA. 1994;91:2537–41.

    CAS  PubMed  Google Scholar 

  66. Vadhan-Raj S, Keating M, LeMaistre A, et al. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med. 1987;317:1545–52.

    CAS  PubMed  Google Scholar 

  67. Schweizerhof M, Stösser S, Kurejova M, et al. Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. Nat Med. 2009;15:802–7.

    CAS  PubMed  Google Scholar 

  68. Khaled YS, Ammori BJ, Elkord E. Myeloid-derived suppressor cells in cancer: recent progress and prospects. Immunol Cell Biol. 2013;91:493–502.

    CAS  PubMed  Google Scholar 

  69. Zhang Y, Cheng S, Zhang M, et al. High-infiltration of tumor-associated macrophages predicts unfavorable clinical outcome for node-negative breast cancer. PLoS One. 2013;8:e76147.

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122:787–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Hao NB, Lu MH, Fan YH, Cao YL, Zhang ZR, et al. Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol. 2012;2012:948098.

    PubMed Central  PubMed  Google Scholar 

  72. Egea L, Hirata Y, Kagnoff MF. GM-CSF: a role in immune and inflammatory reactions in the intestine. Expert Rev Gastroenterol Hepatol. 2010;4:723–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Hirata Y, Egea L, Dann SM, et al. GM-CSF-facilitated dendritic cell recruitment and survival govern the intestinal mucosal response to a mouse enteric bacterial pathogen. Cell Host Microbe. 2010;7:151–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Brosbøl-Ravnborg A, Hvas CL, Agnholt J, et al. Toll-like receptor-induced granulocyte-macrophage colony-stimulating factor secretion is impaired in Crohn’s disease by nucleotide oligomerization domain 2-dependent and -independent pathways. Clin Exp Immunol. 2009;155:487–95.

    PubMed Central  PubMed  Google Scholar 

  75. Korzenik JR, Dieckgraefe BK, Valentine JF, et al. Sargramostim for active Crohn’s disease. N Engl J Med. 2005;352:2193–201.

    CAS  PubMed  Google Scholar 

  76. Valentine JF, Fedorak RN, Feagan B, et al. Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn’s disease: a randomised, double-blind, placebo-controlled, phase 2 study. Gut. 2009;58:1354–62.

    CAS  PubMed  Google Scholar 

  77. Tazawa R, Trapnell BC, Inoue Y, et al. Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2010;181:1345–54.

    CAS  PubMed  Google Scholar 

  78. Kleff V, Sorg UR, Bury C, et al. Gene therapy of beta(c)-deficient pulmonary alveolar proteinosis (beta(c)-PAP): studies in a murine in vivo model. Mol Ther. 2008;16:757–64.

    CAS  PubMed  Google Scholar 

  79. Higano CS, Schellhammer PF, Small EJ, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115:3670–9.

    CAS  PubMed  Google Scholar 

  80. Olivares J, Kumar P, Yu Y, et al. Phase I trial of TGF-{beta}2 antisense GM-CSF gene-modified autologous tumor cell (TAG) vaccine. Clin Cancer Res. 2011;17:183–92.

    CAS  PubMed  Google Scholar 

  81. Bradbury PA, Shepherd FA. Immunotherapy for lung cancer. J Thorac Oncol. 2008;3:S164–70.

    PubMed  Google Scholar 

  82. Holt GE, Disis ML. Immune modulation as a therapeutic strategy for non-small-cell lung cancer. Clin Lung Cancer. 2009;9:S13–9.

    Google Scholar 

  83. Staff C, Mozaffari F, Haller BK, et al. A Phase I safety study of plasmid DNA immunization targeting carcinoembryonic antigen in colorectal cancer patients. Vaccine. 2011;29:6817–22.

    CAS  PubMed  Google Scholar 

  84. Garcia JA, Mekhail T, Elson P, et al. Phase I/II trial of subcutaneous interleukin-2, granulocyte-macrophage colony-stimulating factor and interferon-α in patients with metastatic renal cell carcinoma. BJU Int. 2012;109:63–9.

    CAS  PubMed  Google Scholar 

  85. Lutz E, Yeo CJ, Lillemoe KD, et al. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma: a phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011;253:328–35.

    PubMed Central  PubMed  Google Scholar 

  86. Wang L, Qi X, Sun Y, et al. Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity. Cancer Gene Ther. 2002;9:819–24.

    CAS  PubMed  Google Scholar 

  87. Dranoff G, Crawford AD, Sadelain M, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science. 1994;264:713–6.

    CAS  PubMed  Google Scholar 

  88. Sun X, Hodge LM, Jones HP, et al. Co-expression of granulocyte-macrophage colony-stimulating factor with antigen enhances humoral and tumor immunity after DNA vaccination. Vaccine. 2002;20:1466–74.

    CAS  PubMed  Google Scholar 

  89. Kim W, Seong J, Oh HJ, et al. A novel combination treatment of armed oncolytic adenovirus expressing IL-12 and GM-CSF with radiotherapy in murine hepatocarcinoma. J Radiat Res. 2011;52:646–54.

    CAS  PubMed  Google Scholar 

  90. Roilides E, Blake C, Holmes A, et al. Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae. J Med Vet Mycol. 1996;34:63–9.

    CAS  PubMed  Google Scholar 

  91. Kowanko IC, Ferrante A, Harvey DP, et al. Granulocyte-macrophage colony-stimulating factor augments neutrophil killing of Torulopsis glabrata and stimulates neutrophil respiratory burst and degranulation. Clin Exp Immunol. 1991;83:225–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Newman SL, Gootee L. Colony-stimulating factors activate human macrophages to inhibit intracellular growth of Histoplasma capsulatum yeasts. Infect Immun. 1992;60:4593–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Roilides E, Mertins S, Eddy J, et al. Impairment of neutrophil chemotactic and bactericidal function in children infected with human immunodeficiency virus type 1 and partial reversal after in vitro exposure to granulocyte-macrophage colony-stimulating factor. J Pediatr. 1990;117:531–40.

    CAS  PubMed  Google Scholar 

  94. Page AV, Liles WC. Colony-stimulating factors in the prevention and management of infectious diseases. Infect Dis Clin North Am. 2011;25:803–17.

    PubMed  Google Scholar 

  95. Steinwede K, Tempelhof O, Bolte K, et al. Local delivery of GM-CSF protects mice from lethal pneumococcal pneumonia. J Immunol. 2011;187:5346–56.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Lu H, Xing Z, Brunham RC. GM-CSF transgene-based adjuvant allows the establishment of protective mucosal immunity following vaccination with inactivated Chlamydia trachomatis. J Immunol. 2002;169:6324–31.

    CAS  PubMed  Google Scholar 

  97. Bo L, Wang F, Zhu J, et al. Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: a meta-analysis. Crit Care. 2011;15:R58.

    PubMed  Google Scholar 

  98. Denis M, Ghadirian E. Granulocyte-macrophage colony-stimulating factor restricts growth of tubercle bacilli in human macrophages. Immunol Lett. 1990;24:203–6.

    CAS  PubMed  Google Scholar 

  99. Chroneos ZC, Midde K, Sever-Chroneos Z, et al. Pulmonary surfactant and tuberculosis. Tuberculosis. 2009;89:S10–4.

    PubMed  Google Scholar 

  100. Szeliga J, Daniel DS, Yang CH, et al. Granulocyte-macrophage colony stimulating factor-mediated innate responses in tuberculosis. Tuberculosis. 2008;88:7–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Francisco-Cruz A, Mata-Espinosa D, Estrada-Parra S, Xing Z, Hernández-Pando R. Immunotherapeutic effects of recombinant adenovirus encoding granulocyte-macrophage colony-stimulating factor in experimental pulmonary tuberculosis. Clin Exp Immunol. 2013;171:283–97.

    CAS  PubMed  Google Scholar 

  102. Marlow N, Morris T, Brocklehurst P, et al. A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years. Arch Dis Child Fetal Neonatal Ed. 2013;98(1):F46–53.

    PubMed Central  PubMed  Google Scholar 

  103. Mera S, Tatulescu D, Cismaru C, et al. Multiplex cytokine profiling in patients with sepsis. APMIS. 2011;119:155–63.

    CAS  PubMed  Google Scholar 

  104. Gonzalez-Juarrero M, Hattle JM, Izzo A, et al. Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control mycobacterium tuberculosis infection. J Leukoc Biol. 2005;77:914–22.

    CAS  PubMed  Google Scholar 

  105. Lang RA, Metcalf D, Cuthbertson RA, et al. Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell. 1987;51:675–86.

    CAS  PubMed  Google Scholar 

  106. Zhang X, Divangahi M, Ngai P, et al. Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene. Vaccine. 2007;25:1342–52.

    CAS  PubMed  Google Scholar 

  107. Ryan AA, Wozniak TM, Shklovskaya E, et al. Improved protection against disseminated tuberculosis by Mycobacterium bovis bacillus Calmette-Guerin secreting murine GM-CSF is associated with expansion and activation of APCs. J Immunol. 2007;179:18–24.

    Google Scholar 

  108. Nambiar JK, Ryan AA, Kong CU, et al. Modulation of pulmonary DC function by vaccine-encoded GM-CSF enhances protective immunity against Mycobacterium tuberculosis infection. Eur J Immunol. 2010;40:153–61.

    CAS  PubMed  Google Scholar 

  109. Dou J, Tang Q, Yu F, et al. Investigation of immunogenic effect of the BCG priming and Ag85A- GM-CSF boosting in Balb/c mice model. Immunobiology. 2010;215:133–42.

    CAS  PubMed  Google Scholar 

  110. Zhang X, Divangahi M, Ngai P, et al. Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene. Vaccine. 2007;25:1342–52.

    CAS  PubMed  Google Scholar 

  111. Wang J, Zganiacz A, Xing Z. Enhanced immunogenicity of BCG vaccine by using a viral-based GM-CSF transgene adjuvant formulation. Vaccine. 2002;20:2887–98.

    CAS  PubMed  Google Scholar 

  112. Wang H, Zhang G, Wen Y, et al. Intracerebral administration of recombinant rabies virus expressing GM-CSF prevents the development of rabies after infection with street virus. PLoS One. 2011;6:e25414.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Li N, Yu YZ, Yu WY, et al. Enhancement of the immunogenicity of DNA replicon vaccine of Clostridium botulinum neurotoxin serotype A by GM-CSF gene adjuvant. Immunopharmacol Immunotoxicol. 2011;33:211–9.

    CAS  PubMed  Google Scholar 

  114. Grabstein KH, Urdal DL, Tushinski RJ, et al. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science. 1986;232:506–8.

    CAS  PubMed  Google Scholar 

  115. Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006;354:2034–45.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

A.F.C., O.R.E., and M.A.S., are scholarship holders from the National Council for Science and Technology (CONACYT), Mexico. Point of view and discussion from León Islas is gratefully acknowledged. The graphic design expertise from Ariadna Méndez is gratefully acknowledged. The authors declare not to have any conflict of interest related to publishing this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rogelio Hernandez-Pando.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLS 27 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Francisco-Cruz, A., Aguilar-Santelises, M., Ramos-Espinosa, O. et al. Granulocyte–macrophage colony-stimulating factor: not just another haematopoietic growth factor. Med Oncol 31, 774 (2014). https://doi.org/10.1007/s12032-013-0774-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0774-6

Keywords

Navigation