A Comprehensive Study On The Role Of GM-CSF In Various Diseases
Main Article Content
Abstract
Granulocyte macrophage-colony stimulating factor (GM-CSF), a cytokine, was first discovered to have the ability to stimulate bone marrow progenitors' proliferation and differentiation into granulocytes and macrophages in vitro. Numerous preclinical studies have shown that GM-CSF affects myeloid cells in a variety of tissues, and GM-CSF deletion/depletion studies suggest that it may be a significant therapeutic target in a number of inflammatory and autoimmune diseases, including rheumatoid arthritis. This review is a comprehensive approach to understandthe structure and biology of GM-CSF, its role in different diseases like inflammatory, infectious and autoimmune disorders, beneficial and contradictory effects etc.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Burgess, A. W. & Metcalf, D. The nature and action of granulocyte-macrophage colony stimulating factors. Blood 56, 947–958 (1980).
Shiomi, A. & Usui, T. Pivotal roles of GM-CSF in autoimmunity and inflammation. Mediators Inflamm 2015, (2015).
Ponomarev, E. D. et al. GM-CSF Production by Autoreactive T Cells Is Required for the Activation of Microglial Cells and the Onset of Experimental Autoimmune Encephalomyelitis. The Journal of Immunology 178, 39–48 (2007).
Shi, Y. et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don’t know. Cell Res 16, 126–133 (2006).
McCormick, T. S., Hejal, R. B., Leal, L. O. &Ghannoum, M. A. GM-CSF: Orchestrating the Pulmonary Response to Infection. Front Pharmacol 12, 735443 (2022).
Rösler, B. & Herold, S. Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia-a new therapeutic strategy? Mol Cell Pediatr 3, (2016).
Hansen, G. et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 134, 496–507 (2008).
D A Rozwarski, K. D. R. H. T. B. P. A. K. Refined crystal structure and mutagenesis of human granulocyte-macrophage colony-stimulating factor. Proteins 26, 304–313 (1996).
Carr, P. D. et al. Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration. Cell 104, 291–300 (2001).
Carr, P. D., Conlan, F., Ford, S., Ollis, D. L. & Young, I. G. An improved resolution structure of the human beta common receptor involved in IL-3, IL-5 and GM-CSF signalling which gives better definition of the high-affinity binding epitope. ActaCrystallogr Sect F StructBiolCrystCommun 62, 509–513 (2006).
Lehtonen, A., Matikainen, S., Miettinen, M. &Julkunen, I. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced STAT5 activation and target-gene expression during human monocyte/macrophage differentiation. J LeukocBiol 71, 511–519 (2002).
Perugini, M. et al. Alternative modes of GM-CSF receptor activation revealed using activated mutants of the common β-subunit. Blood 115, 3346–3353 (2010).
Van De Laar, L., Coffer, P. J. &Woltman, A. M. Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. Blood 119, 3383–3393 (2012).
Gao, Y. et al. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 39, 722–732 (2013).
Williams, J. W. et al. Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation. Nat Commun 4, (2013).
Achuthan, A. et al. Granulocyte macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate inflammation. J Clin Invest 126, 3453–3466 (2016).
Lee, M.-C. et al. GM-CSF- and IRF4-Dependent Signaling Can Regulate Myeloid Cell Numbers and the Macrophage Phenotype during Inflammation. J Immunol 202, 3033–3040 (2019).
Weiss, M., Blazek, K., Byrne, A. J., Perocheau, D. P. &Udalova, I. A. IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators Inflamm 2013, (2013).
Ahyi, A.-N. N., Chang, H.-C., Dent, A. L., Nutt, S. L. & Kaplan, M. H. IFN regulatory factor 4 regulates the expression of a subset of Th2 cytokines. J Immunol 183, 1598–1606 (2009).
Okada, Y. et al. Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nat Genet 44, 511–516 (2012).
Shi, H. et al. GM-CSF Primes Proinflammatory Monocyte Responses in Ankylosing Spondylitis. Front Immunol 11, (2020).
Cook, A. D. et al. Granulocyte-macrophage colony-stimulating factor is a key mediator in inflammatory and arthritic pain. Ann Rheum Dis 72, 265–270 (2013).
Cook, A. D., Braine, E. L., Campbell, I. K., Rich, M. J. & Hamilton, J. A. Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res 3, 293–298 (2001).
Lee, M. C. et al. CCL17 blockade as a therapy for osteoarthritis pain and disease. Arthritis Res Ther 20, (2018).
Burmester, G. R. et al. Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor α Monoclonal Antibody: Long-Term Safety and Efficacy in Patients With Rheumatoid Arthritis. Arthritis Rheumatol 70, 679–689 (2018).
Klein-Wieringa, I. R. et al. Inflammatory Cells in Patients with Endstage Knee Osteoarthritis: A Comparison between the Synovium and the Infrapatellar Fat Pad. J Rheumatol 43, 771–778 (2016).
Yasuda K, Takeuchi Y, Hirota K. The pathogenicity of Th17 cells in autoimmune diseases. SeminImmunopathol. 41(3):283–297 (2019).
Haak S, Croxford AL, Kreymborg K, et al. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J Clin Invest. 2009;119(1):61–69.
Codarri L, Gyulveszi G, Tosevski V, et al. RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol. 2011;12(6):560–567. doi: 10.1038/ni.2027
El-Behi M, Ciric B, Dai H, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol. 2011;12(6):568–575. doi: 10.1038/ni.2031
Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN. GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol. 2007;178(1):39–48. doi: 10.4049/jimmunol.178.1.39
King IL, Dickendesher TL, Segal BM. Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood. 2009;113(14):3190–3197. doi: 10.1182/blood-2008-07-168575
Vogel DY, Kooij G, Heijnen PD, et al. GM-CSF promotes migration of human monocytes across the blood brain barrier. Eur J Immunol. 2015;45(6):1808–1819. doi: 10.1002/eji.201444960
Duncker PC, Stoolman JS, Huber AK, Segal BM. GM-CSF promotes chronic disability in experimental autoimmune encephalomyelitis by altering the composition of central nervous system-infiltrating cells, but is dispensable for disease induction. J Immunol. 2018;200(3):966–973.
McQualter JL, Darwiche R, Ewing C, et al. Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J Exp Med. 2001;194(7):873–882. doi: 10.1084/jem.194.7.873
Perrella O, Carrieri PB, De Mercato R, Buscaino GA. Markers of activated T lymphocytes and T cell receptor gamma/delta+ in patients with multiple sclerosis. Eur Neurol. 1993;33(2):152–155. doi: 10.1159/000116923
Aharoni R, Eilam R, Schottlender N, et al. Glatiramer acetate increases T- and B -regulatory cells and decreases granulocyte-macrophage colony-stimulating factor (GM-CSF) in an animal model of multiple sclerosis. J Neuroimmunol. 2020;345:577281. doi: 10.1016/j.jneuroim.2020.
Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12(4):205–217. doi: 10.1038/nrgastro.2015.34
Marks DJ, Rahman FZ, Sewell GW, Segal AW. Crohn’s disease: an immune deficiency state. Clin Rev Allergy Immunol. 2010;38(1):20–31. doi: 10.1007/s12016-009-8133-2
Griseri T, McKenzie BS, Schiering C, Powrie F. Dysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation. Immunity. 2012;37(6):1116–1129. doi: 10.1016/j.immuni.2012.08.025
Griseri T, Arnold IC, Pearson C, et al. Granulocyte macrophage colony-stimulating factor-activated eosinophils promote interleukin-23 driven chronic colitis. Immunity. 2015;43(1):187–199. doi: 10.1016/j.immuni.2015.07.008
Xu Y, Hunt NH, Bao S. The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation. Cell Res. 2008;18(12):1220–1229. doi: 10.1038/cr.2008.310
Dabritz J. Granulocyte macrophage colony-stimulating factor and the intestinal innate immune cell homeostasis in Crohn’s disease. Am J PhysiolGastrointest Liver Physiol. 2014;306(6):G455–465. doi: 10.1152/ajpgi.00409.2013
Pearson C, Thornton EE, McKenzie B, et al. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation. Elife. 2016;5:e10066.
Gathungu G, Zhang Y, Tian X, et al. Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease. World J Gastroenterol. 2018;24(5):623–630. doi: 10.3748/wjg.v24.i5.623
Denson LA, Jurickova I, Karns R, et al. Genetic and transcriptomic variation linked to neutrophil granulocyte-macrophage colony-stimulating factor signaling in pediatriccrohn’s disease. Inflamm Bowel Dis. 2019;25(3):547–560. doi: 10.1093/ibd/izy265
Atzeni F, Gerardi MC, Barilaro G, Masala IF, Benucci M, Sarzi-Puttini P. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review. Expert Rev Clin Immunol. 2018;14(1):69–82. doi: 10.1080/1744666X.2018.1411190
Sakaguchi N, Takahashi T, Hata H, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 2003;426(6965):454–460. doi: 10.1038/nature02119
Guerard S, Boieri M, Hultqvist M, Holmdahl R, Wing K. The SKG mutation in ZAP-70 also confers arthritis susceptibility in C57 black mouse strains. Scand J Immunol. 2016;84(1):3–11. doi: 10.1111/sji.12438
Benham H, Rehaume LM, Hasnain SZ, et al. Interleukin-23 mediates the intestinal response to microbial beta-1,3-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis Rheumatol. 2014;66(7):1755–1767. doi: 10.1002/art.38638
Kwon OC, Lee EJ, Chang EJ, et al. IL-17A(+)GM-CSF(+) neutrophils are the major infiltrating cells in interstitial lung disease in an autoimmune arthritis model. Front Immunol. 2018;9:1544. doi: 10.3389/fimmu.2018.01544
Shiomi A, Usui T, Ishikawa Y, Shimizu M, Murakami K, Mimori T. GM-CSF but not IL-17 is critical for the development of severe interstitial lung disease in SKG mice. J Immunol. 2014;193(2):849–859. doi: 10.4049/jimmunol.1303255
Chen YT, Hsu H, Lin CC, et al. Inflammatory macrophages switch to CCL17-expressing phenotype and promote peritoneal fibrosis. J Pathol. 2020;250(1):55–66. doi: 10.1002/path.5350
Lee KM, Jarnicki A, Achuthan A, et al. CCL17 in inflammation and pain. J Immunol. 2020;205(1):213–222. doi: 10.4049/jimmunol.2000315
Son BK, Sawaki D, Tomida S, et al. Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma. Nat Commun. 2015;6(1):6994. doi: 10.1038/ncomms7994Ye
P, Chen W, Wu J, et al. GM-CSF contributes to aortic aneurysms resulting from SMAD3 deficiency. J Clin Invest. 2013;123(5):2317–2331. doi: 10.1172/JCI67356
Nouri-Aria KT, Masuyama K, Jacobson MR, et al. Granulocyte/macrophage-colony stimulating factor in allergen-induced rhinitis: cellular localization, relation to tissue eosinophilia and influence of topical corticosteroid. Int Arch Allergy Immunol. 1998;117(4):248–254. doi: 10.1159/000024019
Cates EC, Fattouh R, Wattie J, et al. Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism. J Immunol. 2004;173(10):6384–6392. doi: 10.4049/jimmunol.173.10.6384
Yamashita N, Tashimo H, Ishida H, et al. Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF). Cell Immunol. 2002;219(2):92–97. doi: 10.1016/S0008-8749(02)00565-8
Yuan L, Zhang X, Yang M, et al. Airway epithelial integrin beta4 suppresses allergic inflammation by decreasing CCL17 production. ClinSci (Lond). 2020;134(13):1735–1749. doi: 10.1042/CS20191188
Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–185. doi: 10.1038/nature21363
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–867. doi: 10.1038/nature05485
Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–1830. doi: 10.1172/JCI200319451
Boi SK, Buchta CM, Pearson NA, et al. Obesity alters immune and metabolic profiles: new insight from obese-resistant mice on high-fat diet. Obesity (Silver Spring). 2016;24(10):2140–2149. doi: 10.1002/oby.21620
Shaw OM, Pool B, Dalbeth N, Harper JL. The effect of diet-induced obesity on the inflammatory phenotype of non-adipose-resident macrophages in an in vivo model of gout. Rheumatology (Oxford). 2014;53(10):1901–1905. doi: 10.1093/rheumatology/keu174
Kim DH, Sandoval D, Reed JA, et al. The role of GM-CSF in adipose tissue inflammation. Am J PhysiolEndocrinolMetab. 2008;295(5):E1038–1046. doi: 10.1152/ajpendo.00061.2008
Plubell DL, Fenton AM, Wilmarth PA, et al. GM-CSF driven myeloid cells in adipose tissue link weight gain and insulin resistance via formation of 2-aminoadipate. Sci Rep. 2018;8(1):11485. doi: 10.1038/s41598-018-29250-8
Sohn S, Kim J, Seo K, Chae Y, Jung J, Suh J, et al.. Gm-Csf-Based Mobilization Effect in Normal Healthy Donors for Allogeneic Peripheral Blood Stem Cell Transplantation. Bone Marrow Transplant (2002) 30(2):81–6. doi: 10.1038/sj.bmt.1703598
Lazarus HM, Ragsdale CE, Gale RP, Lyman GH. Sargramostim (Rhu Gm-Csf) as Cancer Therapy (Systematic Review) and an Immunomodulator. A Drug Before Its Time Front Immunol (2021) 12:3196. doi: 10.1038/sj.gt.3301885
Spitler LE, Weber RW, Allen RE, Meyer J, Cruickshank S, Garbe E, et al.. Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (Gm-Csf, Sargramostim) Administered for 3 Years as Adjuvant Therapy of Stages Ii (T4), Iii, and Iv Melanoma. J Immunother (2009) 32(6):632–7. doi: 10.1097/CJI.0b013e3181a7d60d
Spitler LE, Cao H, Piironen T, Whiteside TL, Weber RW, Cruickshank S. Biologic Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (Gm-Csf) Antibody Formation in Patients Treated With Gm-Csf (Sargramostim) as Adjuvant Therapy of Melanoma. Am J Clin Oncol (2017) 40(2):207. doi: 10.1097/COC.0000000000000124
Kurbacher CM, Kurbacher JA, Cramer E-M, Rhiem K, Mallman PK, Reichelt R, et al.. Continuous Low-Dose Gm-Csf as Salvage Therapy in Refractory Recurrent Breast or Female Genital Tract Carcinoma. Oncology (2005) 19(4 Suppl 2):23–6.
Huang FF, Barnes PF, Feng Y, Donis R, Chroneos ZC et al. (2011) GM-CSF in the lung protects against lethal influenza infection. Am J Respir Crit Care Med 184: 259–268. 201012-2036OC [pii]; pmid:21474645
Ghoneim HE, Thomas PG, McCullers JA (2013) Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol 191: 1250–1259. jimmunol.1300014 [pii]; pmid:23804714
Schneider C, Nobs SP, Heer AK, Kurrer M, Klinke G et al. (2014) Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. PLoSPathog 10: e1004053. ;PPATHOGENS-D-13-02507 [pii]. pmid:24699679
Subramaniam R, Barnes PF, Fletcher K, Bogarram V, Hillberry Z et al. (2013) Protecting against post-influenza bacterial pneumonia by increasing phagocyte recruitment and ROS production. J Infect Dis. jit830 [pii];
Lin KL, Suzuki Y, Nakano H, Ramsburg E, Gunn MD (2008) CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J Immunol 180: 2562–2572. 180/4/2562 [pii]. pmid:18250467
Jamieson AM, Pasman L, Yu S, Gamradt P, Homer RJ et al. (2013) Role of tissue protection in lethal respiratory viral-bacterial coinfection. Science 340: 1230–1234. science.1233632 [pii]; pmid:23618765
Bermudez L.E., Young, LS. Recombinant human granulocyte-macrophage colony-stimulating factor activates human macrophages to inhibit growth or kill Mycobacterium avium complex. J LeukBiol 1990:48:67-73.
Bermudez L.E., Martinelli J., Petrofsky M., Kolonoski P. and Young L.S. Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibiotics against Mycobacterium avium complex infection in the beige mouse model. J Infec Dis 1994;169:575-80
Denis M., Ghadirian E. Granulocyte-macrophage colony-stimulating factor restricts growth of tubercle bacilli in human macrophages. Immunol Lett 1990;24:203-6.
LeVine AM, Reed JA, Kurak KE, Cianciolo E, Whitsett JA. GM-CSF–deficient mice are susceptible to pulmonary group B streptococcal infection. The Journal of clinical investigation. 1999 Feb 15;103(4):563-9.
Fleischmann, J, Golde, DW, Weisbart, RH, Gasson, JC. Granulocyte-macrophage colony-stimulating factor enhances phagocytosis of bacteria by human neutrophils. Blood 1986. 68:708-711.
Collins, HL, Bancroft, GJ. Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor for phagocytosis of Cryptococcus neoformans. Eur J Immunol 1992. 22:1447-1454.
Chen, GH, et al. Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro. J Immunol 1994. 152:724-734.
Dranoff, G, et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 1994. 264:713-716.
Wright, JR, Youmans, DC. Pulmonary surfactant protein A stimulates chemotaxis of alveolar macrophages. Am J Physiol 1993. 264:L338-L344.
Crouch, EC, Persson, A, Griffin, GL, Chang, D, Senior, RM. Interactions of pulmonary surfactant protein D (SP-D) with human blood leukocytes. Am J Respir Cell MolBiol 1995. 12:410-415.
van Iwaarden, F, Welmers, B, Verhoef, J, Haagsman, HP, van Golde, LMG. Pulmonary surfactant protein A enhances the host-defense mechanisms of rat alveolar macrophages. Am J Respir Cell MolBiol 1990. 2:91-98.
LeVine, AM, et al. Surfactant protein A-deficient mice are susceptible to group B streptococcal infection. J Immunol 1997. 158:4336-4340.
Lopez A, Shannon M, Hercus T. et al. Residue 21 of human granulocyte macrophage colony stimulating factor is critical for biological activity and for high but not low affinity binding. EMBO J 1992, 11: 909 –916.
Koyanagi Y, O'Brien WA, Zhao JQ, Golde DW, Gasson JC, Chen ISY. Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Science 1988, 241: 1673 –1675.
Perno CF, Yarchoan R, Cooney DA. et al. Replication of human immunodeficiency virus in monocytes. :Granulocyte/macrophage colony-stimulating factor (GM-CSF) potentiates viral production yet enhances the antiviral effect mediated by 3×-azido-2×3×-dideoxythymidine (AZT) and other dideoxynucleoside congeners of thymidine. J Exp Med 1989, 169: 933 –951.
Schuitemaker H, Kootstra NA, van Oers MH, van Lambalgen R, Tersmette M, Miedema F. Induction of monocyte proliferation and HIV expression by IL-3 does not interfere with anti-viral activity of zidovudine. Blood 1990, 76: 1490 –1493.
Perno CF, Cooney DA, Gao WY. et al. Effects of bone marrow stimulatory cytokines on human immunodeficiency virus replication and the antiviral activity of dideoxynucleosides in cultures of monocytes/macrophages. Blood 1992, 80: 995 –1003.
Wang J, Roderiquez G, Oravecz T, Norcross A. Cytokine regulation of human immunodeficiency virus type 1 entry and replication in human monocytes/macropohages through modulation of CCR5 expression. J Virol 1998, 72: 7642 –7647.
Folks TM, Justement J, Kinter A, Dinarello CA, Fauci AS. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 1987, 238: 800 –802.
Pomerantz RJ, Feinberg MB, Trono D, Baltimore D. Lipopolysaccharide is a potent monocyte/macrophage specific stimulator of human immunodeficiency virus type 1 expression. J Exp Med 1990, 172: 253 –261.
Kornbluth RS, Oh PS, Munis JR, Cleveland PH, Richman DD. Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. J Exp Med 1989, 169: 1137 –1151.
Hammer SM, Gillis JM, Pinkston P, Rose RM. Effect of zidovudine and granulocyte-macrophage colony stimulating factor on human immunodeficiency virus replication in alveolar macrophages. Blood 1990, 75: 1215 –1219.
Matsuda S, Akagawa K, Honda M, Yokota Y, Takebe Y, Takemon T. Suppression of HIV replication in human monocyte derived macrophages induced by granulocyte macrophage colony stimulating factor. AIDS Res Hum Retroviruses 1995, 11: 1031 –1038.
Di Marzio P, Tse J, Landau N. Chemokine receptor regulation and HIV type 1 tropism in monocyte-macrophages. AIDS Res Hum Retroviruses 1998, 14: 129 –138.
Lin Y, Xu J, Lan H. Tumor-Associated Macrophages in Tumor Metastasis: Biological Roles and Clinical Therapeutic Applications. J HematolOncol (2019) 12(1):1–16. doi: 10.1186/s13045-019-0760-3
Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ. Ccl2 and Interleukin-6 Promote Survival of Human Cd11b+ Peripheral Blood Mononuclear Cells and Induce M2-Type Macrophage Polarization. J BiolChem (2009) 284(49):34342–54. doi: 10.1074/jbc.M109.042671
Owen JL, Torroella-Kouri M, Handel-Fernandez ME, Iragavarapu-Charyulu V. Gm-Csf Up-Regulates the Expression of Ccl2 by T Lymphocytes in Mammary Tumor-Bearing Mice. Int J Mol Med (2007) 20(1):129–36. doi: 10.3892/ijmm.20.1.129
Sierra-Filardi E, Nieto C, Domínguez-Soto Á, Barroso R, Sánchez-Mateos P, Puig-Kroger A, et al.. Ccl2 Shapes Macrophage Polarization by Gm-Csf and M-Csf: Identification of Ccl2/Ccr2-Dependent Gene Expression Profile. J Immunol (2014) 192(8):3858–67. doi: 10.4049/jimmunol.1302821
Jeannin P, Paolini L, Adam C, Delneste Y. The Roles of Csf S on the Functional Polarization of Tumor-Associated Macrophages. FEBS J (2018) 285(4):680–99. doi: 10.1111/febs.14343
Huang D, Song S-J, Wu Z-Z, Wu W, Cui X-Y, Chen J-N, et al.. Epstein–Barr Virus-Induced Vegf and Gm-Csf Drive Nasopharyngeal Carcinoma Metastasis Via Recruitment and Activation of Macrophages. Cancer Res (2017) 77(13):3591–604. doi: 10.1158/0008-5472.CAN-16-2706
Wang H, Jia R, Zhao T, Li X, Lang M, Lan C, et al.. Hif-1α Mediates Tumor-Nerve Interactions Through the Up-Regulation of Gm-Csf in Pancreatic Ductal Adenocarcinoma. Cancer Lett (2019) 453:10–20. doi: 10.1016/j.canlet.2019.03.036
Srinivasan S, Totiger T, Shi C, Castellanos J, Lamichhane P, Dosch AR, et al.. Tobacco Carcinogen–Induced Production of Gm-Csf Activates Creb to Promote Pancreatic Cancer. Cancer Res (2018) 78(21):6146–58. doi: 10.1158/0008-5472.CAN-18-0579
Waghray M, Yalamanchili M, Dziubinski M, Zeinali M, Erkkinen M, Yang H, et al.. Gm-Csf Mediates Mesenchymal–Epithelial Cross-Talk in Pancreatic Cancer. Cancer Discovery (2016) 6(8):886–99. doi: 10.1158/2159-8290.CD-15-0947
Jones TC. Recombinant human GM-CSF: present clinical results and potential use in oncologic and hematologic disorders. Bull Cancer. 1991;78(12):1155-9. PMID: 1786428.
Lazarus HM, Pitts K, Wang T, Lee E, Buchbinder E, Dougan M, Armstrong DG, Paine R 3rd, Ragsdale CE, Boyd T, Rock EP, Gale RP. Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders. Front Immunol. 2023 Jan 5;13:1069444. doi: 10.3389/fimmu.2022.1069444. PMID: 36685591; PMCID: PMC9850113.
Bianchi L, Ginebri A, Hagman JH, Francesconi F, Carboni I, Chimenti S. Local treatment of chronic cutaneous leg ulcers with recombinant human granulocyte‐macrophage colony‐stimulating factor. Journal of the European Academy of Dermatology and Venereology. 2002 Nov;16(6):595-8.
Wexler LH, Weaver-McClure L, Steinberg SM, Jacobson J, Jarosinski P, Avila N, Pizzo PA, Horowitz ME. Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy. Journal of clinical oncology. 1996 Mar;14(3):901-10.