Macrophage polarization in inflammatory diseases

Yan-Cun Liu, Xian-Biao Zou, Yan-Fen Chai, Yong-Ming Yao, Yan-Cun Liu, Xian-Biao Zou, Yan-Fen Chai, Yong-Ming Yao

Abstract

Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.

Keywords: alternatively activated macrophage; immune regulation.; inflammatory diseases; macrophage polarization; signal pathways.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Timeline: advance in research of macrophage polarization.
Figure 2
Figure 2
Signal pathways of macrophage polarization. The figure illustrates several mechanisms underlying macrophage polarization and shows the feedback regulation between M1 and M2 signal pathways. Those include the activation of STAT1 mediated by IFN-γ receptor, increase in IRF5, NF-κB, as well as AP1 expression mediated by Toll-like receptor 4 (TLR4), enhanced AP1 expression mediated by cytokine receptor, activation of STAT6 and increased IRF4 mediated by IL-4 receptor, increased level of PPARγ mediated by fatty acid receptor, and enhanced expression in CREB by TLR4. The feedback regulation between M1 and M2 are implemented by STAT1-STAT6, IRF5-IRF4, NF-κB-PPARγ, AP1-CREB, and AP1-PPARγ, and they play essential roles in the initiation, development, and cessation of inflammatory diseases.

References

    1. Metchnikoff E. Immunity in the Infectious Diseases. New York: Macmillan; 1905.
    1. North RJ. Cellular mediators of anti-Listeria immunity as an enlarged population of short lived, replicating T cells. Kinetics of their production. The Journal of experimental medicine. 1973;138:342–55.
    1. David JR. Lymphocyte mediators and cellular hypersensitivity. The New England journal of medicine. 1973;288:143–9. doi:10.1056/NEJM197301182880311.
    1. Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. The Journal of experimental medicine. 1983;158:670–89.
    1. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual review of immunology. 1989;7:145–73. doi:10.1146/annurev.iy.07.040189.001045.
    1. Abramson SL, Gallin JI. IL-4 inhibits superoxide production by human mononuclear phagocytes. The Journal of immunology. 1990;144:625–30.
    1. Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. The Journal of experimental medicine. 1992;176:287–92.
    1. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nature reviews immunology. 2008;8:958–69. doi:10.1038/nri2448.
    1. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nature immunology. 2010;11:889–96. doi:10.1038/ni.1937.
    1. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604. doi:10.1016/j.immuni.2010.05.007.
    1. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445–55. doi:10.1038/nature12034.
    1. Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nature reviews immunology. 2011;11:750–61. doi:10.1038/nri3088.
    1. Ohmori Y, Hamilton TA. IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages. The Journal of immunology. 1997;159:5474–82.
    1. Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y. et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nature immunology. 2010;11:936–44. doi:10.1038/ni.1920.
    1. Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N. et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nature immunology. 2011;12:231–8. doi:10.1038/ni.1990.
    1. Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-kappaB signaling pathways. Nature immunology. 2011;12:695–708. doi:10.1038/ni.2065.
    1. Schonthaler HB, Guinea-Viniegra J, Wagner EF. Targeting inflammation by modulating the Jun/AP-1 pathway. Annals of the rheumatic diseases. 2011;70(Suppl 1):i109–12. doi:10.1136/ard.2010.140533.
    1. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L. et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007;447:1116–20. doi:10.1038/nature05894.
    1. Bouhlel MA, Derudas B, Rigamonti E, Dievart R, Brozek J, Haulon S. et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell metabolism. 2007;6:137–43. doi:10.1016/j.cmet.2007.06.010.
    1. Ruffell D, Mourkioti F, Gambardella A, Kirstetter P, Lopez RG, Rosenthal N. et al. A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:17475–80. doi:10.1073/pnas.0908641106.
    1. Shaughnessy LM, Swanson JA. The role of the activated macrophage in clearing Listeria monocytogenes infection. Frontiers in bioscience: a journal and virtual library. 2007;12:2683–92.
    1. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. The Journal of clinical investigation. 2012;122:787–95. doi:10.1172/JCI59643.
    1. Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG. The Pathogenesis of Sepsis. Annual review of pathology: mechanisms of disease. 2011;6:19–48. doi:10.1146/annurev-pathol-011110-130327.
    1. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nature reviews immunology. 2011;11:723–37. doi:10.1038/nri3073.
    1. Thompson LJ, Dunstan SJ, Dolecek C, Perkins T, House D, Dougan G. et al. Transcriptional response in the peripheral blood of patients infected with Salmonella enterica serovar Typhi. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:22433–8. doi:10.1073/pnas.0912386106.
    1. Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D. et al. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:14978–83. doi:10.1073/pnas.0809784106.
    1. Hoeve MA, Nash AA, Jackson D, Randall RE, Dransfield I. Influenza virus A infection of human monocyte and macrophage subpopulations reveals increased susceptibility associated with cell differentiation. PloS one. 2012;7:e29443.. doi:10.1371/journal.pone.0029443.
    1. Page C, Goicochea L, Matthews K, Zhang Y, Klover P, Holtzman MJ. et al. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection. Journal of virology. 2012;86:13334–49. doi:10.1128/JVI.01689-12.
    1. Shirey KA, Pletneva LM, Puche AC, Keegan AD, Prince GA, Blanco JC. et al. Control of RSV-induced lung injury by alternatively activated macrophages is IL-4R alpha-, TLR4-, and IFN-beta-dependent. Mucosal immunology. 2010;3:291–300. doi:10.1038/mi.2010.6.
    1. Liddiard K, Rosas M, Davies LC, Jones SA, Taylor PR. Macrophage heterogeneity and acute inflammation. European journal of immunology. 2011;41:2503–8. doi:10.1002/eji.201141743.
    1. Sitia G, Iannacone M, Aiolfi R, Isogawa M, van Rooijen N, Scozzesi C. et al. Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis. PLoS pathogens. 2011;7:e1002061.. doi:10.1371/journal.ppat.1002061.
    1. Hussell T, Bell TJ. Alveolar macrophages: plasticity in a tissue-specific context. Nature reviews immunology. 2014;14:81–93. doi:10.1038/nri3600.
    1. Tan J, Sattentau QJ. The HIV-1-containing macrophage compartment: a perfect cellular niche? Trends in microbiology. 2013 doi:10.1016/j.tim.2013.05.001.
    1. Herbein G, Varin A. The macrophage in HIV-1 infection: from activation to deactivation? Retrovirology. 2010;7:33.. doi:10.1186/1742-4690-7-33.
    1. Jensen KD, Wang Y, Wojno ED, Shastri AJ, Hu K, Cornel L. et al. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. Cell host & microbe. 2011;9:472–83. doi:10.1016/j.chom.2011.04.015.
    1. Mylonas KJ, Nair MG, Prieto-Lafuente L, Paape D, Allen JE. Alternatively activated macrophages elicited by helminth infection can be reprogrammed to enable microbial killing. The Journal of immunology. 2009;182:3084–94. doi:10.4049/jimmunol.0803463.
    1. Lefevre L, Lugo-Villarino G, Meunier E, Valentin A, Olagnier D, Authier H. et al. The C-type lectin receptors Dectin-1, MR, and SIGNR3 contribute both positively and negatively to the macrophage response to Leishmania infantum. Immunity. 2013;38:1038–49. doi:10.1016/j.immuni.2013.04.010.
    1. Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC, Smith AM. et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS pathogens. 2009;5:e1000371.. doi:10.1371/journal.ppat.1000371.
    1. Herbert DR, Orekov T, Roloson A, Ilies M, Perkins C, O'Brien W. et al. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. The Journal of immunology. 2010;184:6438–46. doi:10.4049/jimmunol.0902009.
    1. Bowcutt R, Bell LV, Little M, Wilson J, Booth C, Murray PJ. et al. Arginase-1-expressing macrophages are dispensable for resistance to infection with the gastrointestinal helminth Trichuris muris. Parasite immunology. 2011;33:411–20. doi:10.1111/j.1365-3024.2011.01300.x.
    1. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145:341–55. doi:10.1016/j.cell.2011.04.005.
    1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G. et al. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121:948–54. doi:10.1161/CIRCULATIONAHA.109.192666.
    1. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339:161–6. doi:10.1126/science.1230719.
    1. Fuster JJ, Fernandez P, Gonzalez-Navarro H, Silvestre C, Nabah YN, Andres V. Control of cell proliferation in atherosclerosis: insights from animal models and human studies. Cardiovascular research. 2010;86:254–64. doi:10.1093/cvr/cvp363.
    1. Mestas J, Ley K. Monocyte-endothelial cell interactions in the development of atherosclerosis. Trends in cardiovascular medicine. 2008;18:228–32. doi:10.1016/j.tcm.2008.11.004.
    1. Kirbis S, Breskvar UD, Sabovic M, Zupan I, Sinkovic A. Inflammation markers in patients with coronary artery disease--comparison of intracoronary and systemic levels. Wiener klinische Wochenschrift. 2010;122(Suppl 2):31–4. doi:10.1007/s00508-010-1343-z.
    1. Khallou-Laschet J, Varthaman A, Fornasa G, Compain C, Gaston AT, Clement M. et al. Macrophage plasticity in experimental atherosclerosis. PloS one. 2010;5:e8852.. doi:10.1371/journal.pone.0008852.
    1. Tsimikas S, Miller YI. Oxidative modification of lipoproteins: mechanisms, role in inflammation and potential clinical applications in cardiovascular disease. Current pharmaceutical design. 2011;17:27–37.
    1. Handberg A, Skjelland M, Michelsen AE, Sagen EL, Krohg-Sorensen K, Russell D. et al. Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability. Stroke, a journal of cerebral circulation. 2008;39:3092–5. doi:10.1161/STROKEAHA.108.517128.
    1. Huo Y, Zhao L, Hyman MC, Shashkin P, Harry BL, Burcin T. et al. Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004;110:2024–31. doi:10.1161/01.CIR.0000143628.37680.F6.
    1. Mallat Z, Gojova A, Marchiol-Fournigault C, Esposito B, Kamate C, Merval R. et al. Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circulation research. 2001;89:930–4.
    1. Thorp E, Tabas I. Mechanisms and consequences of efferocytosis in advanced atherosclerosis. Journal of leukocyte biology. 2009;86:1089–95. doi:10.1189/jlb.0209115.
    1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA: the journal of the American Medical Association. 2010;303:235–41. doi:10.1001/jama.2009.2014.
    1. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J. et al. A potential decline in life expectancy in the United States in the 21st century. The New England journal of medicine. 2005;352:1138–45. doi:10.1056/NEJMsr043743.
    1. Grundy SM. Metabolic complications of obesity. Endocrine. 2000;13:155–65. doi:10.1385/ENDO:13:2:155.
    1. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature medicine. 2011;17:179–88. doi:10.1038/nm.2279.
    1. Biswas SK, Mantovani A. Orchestration of metabolism by macrophages. Cell metabolism. 2012;15:432–7. doi:10.1016/j.cmet.2011.11.013.
    1. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annual review of physiology. 2010;72:219–46. doi:10.1146/annurev-physiol-021909-135846.
    1. Odegaard JI, Chawla A. Mechanisms of macrophage activation in obesity-induced insulin resistance. Nature clinical practice endocrinology & metabolism. 2008;4:619–26. doi:10.1038/ncpendmet0976.
    1. Kosteli A, Sugaru E, Haemmerle G, Martin JF, Lei J, Zechner R. et al. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. The Journal of clinical investigation. 2010;120:3466–79. doi:10.1172/JCI42845.
    1. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T. et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature. 2011;480:104–8. doi:10.1038/nature10653.
    1. Chinetti-Gbaguidi G, Staels B. Macrophage polarization in metabolic disorders: functions and regulation. Current opinion in lipidology. 2011;22:365–72. doi:10.1097/MOL.0b013e32834a77b4.
    1. Mantovani A. Cancer: Inflaming metastasis. Nature. 2009;457:36–7. doi:10.1038/457036b.
    1. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141:39–51. doi:10.1016/j.cell.2010.03.014.
    1. Wei Q, Fang W, Ye L, Shen L, Zhang X, Fei X, Density of tumor associated macrophage correlates with lymph node metastasis in papillary thyroid carcinoma. Thyroid: official journal of the American Thyroid Association; 2012. doi:10.1089/thy.2011-0452.
    1. Shirabe K, Mano Y, Muto J, Matono R, Motomura T, Toshima T. et al. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surgery today. 2012;42:1–7. doi:10.1007/s00595-011-0058-8.
    1. Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T. et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. The New England journal of medicine. 2010;362:875–85. doi:10.1056/NEJMoa0905680.
    1. Prada CE, Jousma E, Rizvi TA, Wu J, Dunn RS, Mayes DA. et al. Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition. Acta neuropathologica. 2013;125:159–68. doi:10.1007/s00401-012-1056-7.
    1. Wang B, Li Q, Qin L, Zhao S, Wang J, Chen X. Transition of tumor-associated macrophages from MHC class II(hi) to MHC class II(low) mediates tumor progression in mice. BMC immunology. 2011;12:43.. doi:10.1186/1471-2172-12-43.
    1. Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG. et al. Macrophage polarization in tumour progression. Seminars in cancer biology. 2008;18:349–55. doi:10.1016/j.semcancer.2008.03.004.
    1. Gordon S. Alternative activation of macrophages. Nature reviews immunology. 2003;3:23–35. doi:10.1038/nri978.
    1. Heuff G, Oldenburg HS, Boutkan H, Visser JJ, Beelen RH, Van Rooijen N. et al. Enhanced tumour growth in the rat liver after selective elimination of Kupffer cells. Cancer immunology, immunotherapy: CII. 1993;37:125–30.
    1. Pollard JW. Trophic macrophages in development and disease. Nature reviews immunology. 2009;9:259–70. doi:10.1038/nri2528.
    1. Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL. et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes & development. 2010;24:241–55. doi:10.1101/gad.1874010.
    1. Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER. et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer research. 2004;64:7022–9. doi:10.1158/0008-5472.CAN-04-1449.
    1. Kitamura T, Kometani K, Hashida H, Matsunaga A, Miyoshi H, Hosogi H. et al. SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nature genetics. 2007;39:467–75. doi:10.1038/ng1997.
    1. Ruffell B, Affara NI, Coussens LM. Differential macrophage programming in the tumor microenvironment. Trends in immunology. 2012;33:119–26. doi:10.1016/j.it.2011.12.001.
    1. Doedens AL, Stockmann C, Rubinstein MP, Liao D, Zhang N, DeNardo DG. et al. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer research. 2010;70:7465–75. doi:10.1158/0008-5472.CAN-10-1439.
    1. Imtiyaz HZ, Williams EP, Hickey MM, Patel SA, Durham AC, Yuan LJ. et al. Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation. The Journal of clinical investigation. 2010;120:2699–714. doi:10.1172/JCI39506.
    1. Harris HE, Andersson U, Pisetsky DS. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nature reviews Rheumatology. 2012;8:195–202. doi:10.1038/nrrheum.2011.222.
    1. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer cell. 2013;23:277–86. doi:10.1016/j.ccr.2013.02.013.
    1. Rolny C, Mazzone M, Tugues S, Laoui D, Johansson I, Coulon C. et al. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer cell. 2011;19:31–44. doi:10.1016/j.ccr.2010.11.009.
    1. Moreira AP, Hogaboam CM. Macrophages in allergic asthma: fine-tuning their pro- and anti-inflammatory actions for disease resolution. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2011;31:485–91. doi:10.1089/jir.2011.0027.
    1. Moreira AP, Cavassani KA, Hullinger R, Rosada RS, Fong DJ, Murray L. et al. Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore-induced allergic airway disease. The Journal of allergy and clinical immunology. 2010;126:712–21. doi:10.1016/j.jaci.2010.06.010.
    1. Kim YK, Oh SY, Jeon SG, Park HW, Lee SY, Chun EY. et al. Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma. The Journal of immunology. 2007;178:5375–82.
    1. Naura AS, Zerfaoui M, Kim H, Abd Elmageed ZY, Rodriguez PC, Hans CP. et al. Requirement for inducible nitric oxide synthase in chronic allergen exposure-induced pulmonary fibrosis but not inflammation. The Journal of immunology. 2010;185:3076–85. doi:10.4049/jimmunol.0904214.
    1. Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. The Lancet infectious diseases. 2013;13:260–8. doi:10.1016/S1473-3099(13)70001-X.
    1. Jiang LN, Yao YM, Sheng ZY. The role of regulatory T cells in the pathogenesis of sepsis and its clinical implication. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2012;32:341–9. doi:10.1089/jir.2011.0080.
    1. Delano MJ, Scumpia PO, Weinstein JS, Coco D, Nagaraj S, Kelly-Scumpia KM. et al. MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. The Journal of experimental medicine. 2007;204:1463–74. doi:10.1084/jem.20062602.
    1. Ruffell B, Au A, Rugo HS, Esserman LJ, Hwang ES, Coussens LM. Leukocyte composition of human breast cancer. Proceedings of the National Academy of Sciences of the United States of America. 2012;109:2796–801. doi:10.1073/pnas.1104303108.
    1. Raes G, Van den Bergh R, De Baetselier P, Ghassabeh GH, Scotton C, Locati M. et al. Arginase-1 and Ym1 are markers for murine, but not human, alternatively activated myeloid cells. The Journal of immunology. 2005;174:6561–2.
    1. Murray PJ, Wynn TA. Obstacles and opportunities for understanding macrophage polarization. Journal of leukocyte biology. 2011;89:557–63. doi:10.1189/jlb.0710409.
    1. 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. The Journal of biological chemistry. 2009;284:34342–54. doi:10.1074/jbc.M109.042671.
    1. Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD. Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation. The Journal of immunology. 2007;178:5245–52.
    1. Lu M, Sarruf DA, Talukdar S, Sharma S, Li P, Bandyopadhyay G. et al. Brain PPAR-gamma promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones. Nature medicine. 2011;17:618–22. doi:10.1038/nm.2332.
    1. Charo IF. Macrophage polarization and insulin resistance: PPARgamma in control. Cell metabolism. 2007;6:96–8. doi:10.1016/j.cmet.2007.07.006.
    1. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W. et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011;331:1612–6. doi:10.1126/science.1198443.
    1. Liu G, Yang H. Modulation of macrophage activation and programming in immunity. Journal of cellular physiology. 2013;228:502–12. doi:10.1002/jcp.24157.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir