Medical Oncology

, 31:774 | Cite as

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

  • Alejandro Francisco-Cruz
  • Miguel Aguilar-Santelises
  • Octavio Ramos-Espinosa
  • Dulce Mata-Espinosa
  • Brenda Marquina-Castillo
  • Jorge Barrios-Payan
  • Rogelio Hernandez-PandoEmail author
Review Article


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.


Haematopoietic growth factor Granulocyte–macrophage colony-stimulating factor Innate immunity Adaptive immunity 



Acute myeloid leukaemia


Alveolar macrophage


Bone marrow


Cytokine inducible SH2-domain


Dendritic cell


GM-CSFRα subunit-associated protein


Invariant natural killer T


IκB kinase



Mitogen-activated kinase-like protein


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


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


Phosphatidylinositol 3 kinase


Protein kinase C


Pulmonary alveolar proteinosis


Recombinant human GM-CSF


Recombinant human granulocyte colony-stimulating factor


Signal transducers and activators of transcription


SRC-like adapter protein


Toll-like receptor



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.

Supplementary material

12032_2013_774_MOESM1_ESM.xls (28 kb)
Supplementary material 1 (XLS 27 kb)


  1. 1.
    Metcalf D. Hematopoietic cytokines. Blood. 2008;111:485–91.PubMedGoogle Scholar
  2. 2.
    Bradley TR, Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966;44:287–99.PubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 5.
    Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008;8:533–44.PubMedGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 7.
    Armitage JO. Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1998;92:4491–508.PubMedGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.PubMedGoogle Scholar
  10. 10.
    Hamilton JA, Anderson GP. GM-CSF biology. Growth Factors. 2004;22:225–31.PubMedGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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.PubMedCentralPubMedGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 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.PubMedCentralPubMedGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedCentralPubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.PubMedGoogle Scholar
  29. 29.
    Leukine® Prescribing information. Available at Accessed on September 2013.
  30. 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.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Crawford J, Armitage J, Balducci L, et al. Myeloid growth factors. J Natl Compr Canc Netw. 2009;7:64–83.PubMedGoogle Scholar
  32. 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.PubMedGoogle Scholar
  33. 33.
    The FDA Safety Information and Adverse Event Reporting Program, 2008. Leukine safety information Available at, Accessed on October 2013.
  34. 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.PubMedCentralPubMedGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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.PubMedGoogle Scholar
  39. 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.PubMedGoogle Scholar
  40. 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.PubMedGoogle Scholar
  41. 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.PubMedCentralPubMedGoogle Scholar
  42. 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.PubMedGoogle Scholar
  43. 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.PubMedCentralPubMedGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. 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.PubMedGoogle Scholar
  46. 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. 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.PubMedGoogle Scholar
  48. 48.
    Krausgruber T, Blazek K, Smallie T, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011;12:231–8.PubMedGoogle Scholar
  49. 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.PubMedGoogle Scholar
  50. 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.PubMedGoogle Scholar
  51. 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.PubMedGoogle Scholar
  52. 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.PubMedGoogle Scholar
  53. 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.PubMedGoogle Scholar
  54. 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.PubMedCentralPubMedGoogle Scholar
  55. 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.PubMedGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. 57.
    Exley MA, Koziel MJ. To be or not to be NKT: natural killer T cells in the liver. Hepatology. 2004;40:1033–40.PubMedGoogle Scholar
  58. 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.PubMedGoogle Scholar
  59. 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.PubMedGoogle Scholar
  60. 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.PubMedGoogle Scholar
  61. 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.PubMedGoogle Scholar
  62. 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.PubMedGoogle Scholar
  63. 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.Google Scholar
  64. 64.
    Stösser S, Schweizerhof M, Kuner R. Hematopoietic colony-stimulating factors: new players in tumor-nerve interactions. J Mol Med. 2011;89:321–9.PubMedCentralPubMedGoogle Scholar
  65. 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.PubMedGoogle Scholar
  66. 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.PubMedGoogle Scholar
  67. 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.PubMedGoogle Scholar
  68. 68.
    Khaled YS, Ammori BJ, Elkord E. Myeloid-derived suppressor cells in cancer: recent progress and prospects. Immunol Cell Biol. 2013;91:493–502.PubMedGoogle Scholar
  69. 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.PubMedCentralPubMedGoogle Scholar
  70. 70.
    Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122:787–95.PubMedCentralPubMedGoogle Scholar
  71. 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.PubMedCentralPubMedGoogle Scholar
  72. 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.PubMedCentralPubMedGoogle Scholar
  73. 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.PubMedCentralPubMedGoogle Scholar
  74. 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.PubMedCentralPubMedGoogle Scholar
  75. 75.
    Korzenik JR, Dieckgraefe BK, Valentine JF, et al. Sargramostim for active Crohn’s disease. N Engl J Med. 2005;352:2193–201.PubMedGoogle Scholar
  76. 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.PubMedGoogle Scholar
  77. 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.PubMedGoogle Scholar
  78. 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.PubMedGoogle Scholar
  79. 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.PubMedGoogle Scholar
  80. 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.PubMedGoogle Scholar
  81. 81.
    Bradbury PA, Shepherd FA. Immunotherapy for lung cancer. J Thorac Oncol. 2008;3:S164–70.PubMedGoogle Scholar
  82. 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. 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.PubMedGoogle Scholar
  84. 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.PubMedGoogle Scholar
  85. 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.PubMedCentralPubMedGoogle Scholar
  86. 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.PubMedGoogle Scholar
  87. 87.
    Dranoff G, Crawford AD, Sadelain M, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science. 1994;264:713–6.PubMedGoogle Scholar
  88. 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.PubMedGoogle Scholar
  89. 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.PubMedGoogle Scholar
  90. 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.PubMedGoogle Scholar
  91. 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.PubMedCentralPubMedGoogle Scholar
  92. 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.PubMedCentralPubMedGoogle Scholar
  93. 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.PubMedGoogle Scholar
  94. 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.PubMedGoogle Scholar
  95. 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.PubMedCentralPubMedGoogle Scholar
  96. 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.PubMedGoogle Scholar
  97. 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.PubMedGoogle Scholar
  98. 98.
    Denis M, Ghadirian E. Granulocyte-macrophage colony-stimulating factor restricts growth of tubercle bacilli in human macrophages. Immunol Lett. 1990;24:203–6.PubMedGoogle Scholar
  99. 99.
    Chroneos ZC, Midde K, Sever-Chroneos Z, et al. Pulmonary surfactant and tuberculosis. Tuberculosis. 2009;89:S10–4.PubMedGoogle Scholar
  100. 100.
    Szeliga J, Daniel DS, Yang CH, et al. Granulocyte-macrophage colony stimulating factor-mediated innate responses in tuberculosis. Tuberculosis. 2008;88:7–20.PubMedCentralPubMedGoogle Scholar
  101. 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.PubMedGoogle Scholar
  102. 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.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Mera S, Tatulescu D, Cismaru C, et al. Multiplex cytokine profiling in patients with sepsis. APMIS. 2011;119:155–63.PubMedGoogle Scholar
  104. 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.PubMedGoogle Scholar
  105. 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.PubMedGoogle Scholar
  106. 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.PubMedGoogle Scholar
  107. 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. 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.PubMedGoogle Scholar
  109. 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.PubMedGoogle Scholar
  110. 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.PubMedGoogle Scholar
  111. 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.PubMedGoogle Scholar
  112. 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.PubMedCentralPubMedGoogle Scholar
  113. 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.PubMedGoogle Scholar
  114. 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.PubMedGoogle Scholar
  115. 115.
    Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006;354:2034–45.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Alejandro Francisco-Cruz
    • 1
    • 2
  • Miguel Aguilar-Santelises
    • 2
  • Octavio Ramos-Espinosa
    • 1
  • Dulce Mata-Espinosa
    • 1
  • Brenda Marquina-Castillo
    • 1
  • Jorge Barrios-Payan
    • 1
  • Rogelio Hernandez-Pando
    • 1
    Email author
  1. 1.Department of PathologyNational Institute of Medical Sciences and Nutrition “Salvador Zubiran”México CityMexico
  2. 2.Department of Immunology, National School of Biological SciencesNational Polytechnic InstituteMéxico CityMexico

Personalised recommendations