Are M1 and M2 macrophages Effectual Players in Pathological Conditions?
Download PDF

Keywords

M1
M2
Macrophages
Inflammation
Polarization

DOI

10.26689/par.v6i3.3962

Submitted : 2022-04-30
Accepted : 2022-05-15
Published : 2022-05-30

Abstract

Pathologic inflammatory conditions are frequently correlated with dynamic alterations through macrophage activation, with classically activated M1 cells associated with promoting and sustaining inflammation and M2 cells implicated in resolving or smoldering chronic inflammation. Inflammation is a common feature of various chronic diseases, and it has direct involvement in the emergence and progression of these conditions. Macrophages participate in an autoregulatory loop characterizing inflammatory process, as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during inflammation. Therefore, balancing the ratio of M1/M2 macrophages can help to ameliorate the inflammatory landscape of pathological conditions. This review will explore the role of macrophage polarization in distant pathological inflammatory conditions, such as cancer, autoimmunity, renal inflammation, stroke, and atherosclerosis, while sharing macrophage-driven pathogenesis.

References

DiPietro LA, Wilgus TA, Koh TJ, 2021, Macrophages in Healing Wounds: Paradoxes and Paradigms. International Journal of Molecular Sciences, 22(2): 950.

Epelman S, Lavine KJ, Randolph GJ, 2014, Origin and Functions of Tissue Macrophages. Immunity, 41: 21-35.

Haniffa M, Bigley V, Collin M, 2015, Human Mononuclear Phagocyte System Reunited. Seminars in Cell & Developmental Biology, 41: 59-69.

Laskin DL, Sunil VR, Gardner CR, et al., 2011, Macrophages and Tissue Injury: Agents of Defense or Destruction?. Annu Rev Pharmacol Toxicol, 51: 267-288.

Bruno A, Pagani A, Pulze L, et al., 2014, Orchestration of Angiogenesis by Immune Cells. Front Oncol, 4: 131.

Bruno A, Pagani A, Magnani E, et al., 2014, Inflammatory Angiogenesis and the Tumor Microenvironment as Targets for Cancer Therapy and Prevention. Cancer Treat Res, 159: 401-426.

Noonan DM, De Lerma Barbaro A, Vannini N, et al., 2008, Inflammation, Inflammatory Cells and Angiogenesis: Decisions and Indecisions. Cancer Metastasis Rev, 27(1): 31-40.

Jeannin P, Paolini L, Adam C, et al., 2018, The Roles of CSFs on the Functional Polarization of Tumor-Associated Macrophages. Febs J, 285(4): 680-699.

Abdollahi E, Momtazi AA, Johnston TP, et al., 2018, Therapeutic Effects of Curcumin in Inflammatory and Immune-Mediated Diseases: A Nature-Made Jack-of-All-Trades?. J Cell Physiol, 233(2): 830-848.

Sica A, Schioppa T, Mantovani A, et al., 2006, Tumour-Associated Macrophages Are a Distinct M2 Polarised Population Promoting Tumour Progression: Potential Targets of Anti-Cancer Therapy. Eur J Cancer, 42(6): 717-727.

Stout RD, Jiang C, Matta B, et al., 2005, Macrophages Sequentially Change Their Functional Phenotype in Response to Changes in Microenvironmental Influences. J Immunol 2005, 175(1): 342-349.

Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al., 2018, Macrophage Plasticity, Polarization, and Function in Health and Disease. J Cell Physiol, 233(9): 6425-6440.

Chistiakov DA, Bobryshev YV, Nikiforov NG, et al., 2015, Macrophage Phenotypic Plasticity in Atherosclerosis: The Associated Features and the Peculiarities of the Expression of Inflammatory Genes. Int J Cardiol, 184: 436-445.

Takeda N, O’Dea EL, Doedens A, et al., 2010, Differential Activation and Antagonistic Function of HIF-{Alpha} Isoforms in Macrophages Are Essential for NO Homeostasis. Genes Dev, 24(5): 491-501.

Bogdan C, 2001, Nitric Oxide and the Immune Response. Nat Immunol, 2(10): 907-916.

Hao N-B, Lu M-H, Fan Y-H, et al., 2012, Macrophages in Tumor Microenvironments and the Progression of Tumors. Clinical and Developmental Immunology, 2012: 948098.

Xu M, Mizoguchi I, Morishima N, et al., 2010, Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27. Clinical and Developmental Immunology, 2010: 832454.

Colombo MP, Trinchieri G, 2002, Interleukin-12 in Anti-Tumor Immunity and Immunotherapy. Cytokine & Growth Factor Reviews, 13(2): 155-168.

Liu Z, Ran Y, Huang S, et al., 2017, Curcumin Protects Against Ischemic Stroke by Titrating Microglia/Macrophage Polarization. Frontiers in Aging Neuroscience, 9: 233.

Gao S, Zhou J, Liu N, et al., 2015, Curcumin Induces M2 Macrophage Polarization by Secretion IL-4 and/or IL-13. Journal of Molecular and Cellular Cardiology, 85: 131-139.

Li B, Hu Y, Zhao Y, et al., 2017, Attenuates Titanium Particle-Induced Inflammation by Regulating Macrophage Polarization In Vitro and In Vivo. Frontiers in Immunology, 8: 55.

Mantovani A, Sozzani S, Locati M, et al., 2002, Macrophage Polarization: Tumor-Associated Macrophages as a Paradigm for Polarized M2 Mononuclear Phagocytes. Trends in Immunology, 23(11): 549-555.

Gordon S, 2003, Alternative Activation of Macrophages. Nature Reviews Immunology, 3: 23-35.

Gordon S, Martinez FO, 2010, Alternative Activation of Macrophages: Mechanism and Functions. Immunity, 32(5): 593-604.

Mills C, 2012, M1 and M2 Macrophages: Oracles of Health and Disease. Critical Reviews in Immunology 2012, 32(6): 463-488.

Murray PJ, Wynn TA, 2011, Protective and Pathogenic Functions of Macrophage Subsets. Nature Reviews Immunology, 11: 723-737.

Vakili?Ghartavol R, Mombeiny R, Salmaninejad A, et al., 2018, Tumor?Associated Macrophages and Epithelial–Mesenchymal Transition in Cancer: Nanotechnology Comes into View. Journal of Cellular Physiology, 233(12): 9223-9236.

Salmaninejad A, Valilou SF, Soltani A, et al., 2019, Tumor-Associated Macrophages: Role in Cancer Development and Therapeutic Implications. Cellular Oncology, 42(5): 591-608.

Mohammadi A, Blesso CN, Barreto GE, et al., 2019, Macrophage Plasticity, Polarization and Function in Response to Curcumin, A Diet-Derived Polyphenol, as an Immunomodulatory Agent. The Journal of Nutritional Biochemistry, 66: 1-16.

Choi HM, Moon SY, Yang HI, et al., 2021, Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics. International Journal of Molecular Sciences, 22(4): 1737.

Vannuccini S, Clifton VL, Fraser IS, et al., 2016, Infertility and Reproductive Disorders: Impact of Hormonal and Inflammatory Mechanisms on Pregnancy Outcome. Human Reproduction Update, 22(1): 104-115.

Mohammadi S, Abdollahi E, Nezamnia M, et al., 2021, Adoptive Transfer of Tregs: A Novel Strategy for Cell-Based Immunotherapy in Spontaneous Abortion: Lessons from Experimental Models. International Immunopharmacology, 90: 107195.

Xu G, Feng L, Song P, et al., 2016, Isomeranzin Suppresses Inflammation by Inhibiting M1 Macrophage Polarization Through the NF-?b And ERK Pathway. International Immunopharmacology, 38: 175-185.

Murray PJ, 2017, Macrophage Polarization. Annual Review of Physiology, 79: 541-566.

Sica A, Bronte V, 2007, Altered Macrophage Differentiation and Immune Dysfunction in Tumor Development. J Clin Invest, 117: 1155-1166.

Pauleau AL, Rutschman R, Lang R, et al., 2004, Enhancer-Mediated Control of Macrophage-Specific Arginase I Expression. J Immunol, 172(12): 7565-7573.

Lang R, Patel D, Morris JJ, et al., 2002, Shaping Gene Expression in Activated and Resting Primary Macrophages by IL-10. J Immunol, 169(5): 2253-2263.

Whyte CS, Bishop ET, Ruckerl D, et al., 2011, Suppressor of Cytokine Signaling (SOCS)1 Is a Key Determinant of Differential Macrophage Activation and Function. J Leukoc Biol, 90(5): 845-854.

Liu Y, Stewart KN, Bishop E, et al., 2008, Unique Expression of Suppressor of Cytokine Signaling 3 Is Essential for Classical Macrophage Activation in Rodents In Vitro and In Vivo. J Immunol, 180(9): 6270-6278.

Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, et al., 2007, Macrophage-Specific PPARgamma Controls Alternative Activation and Improves Insulin Resistance. Nature, 447(7148): 1116-1120.

Kang K, Reilly SM, Karabacak V, et al., 2008, Adipocyte-Derived Th2 Cytokines and Myeloid PPARdelta Regulate Macrophage Polarization and Insulin Sensitivity. Cell Metab, 7(6): 485-495.

Cao Z, Sun X, Icli B, et al., 2010, Role of Kruppel-Like Factors in Leukocyte Development, Function, and Disease. Blood, 116(22): 4404-4414.

Liao X, Sharma N, Kapadia F, et al., 2011, Kruppel-Like Factor 4 Regulates Macrophage Polarization. J Clin Invest, 121(7): 2736-2749.

Szanto A, Balint BL, Nagy ZS, et al., 2010, STAT6 Transcription Factor Is a Facilitator of the Nuclear Receptor PPAR?-Regulated Gene Expression in Macrophages and Dendritic Cells. Immunity, 33(5): 699-712.

Mahabeleshwar GH, Kawanami D, Sharma N, et al., 2011, The Myeloid Transcription Factor KLF2 Regulates the Host Response to Polymicrobial Infection and Endotoxic Shock. Immunity, 34(5): 715-728.

Pello OM, De Pizzol M, Mirolo M, et al., 2012, Role of c-MYC in Alternative Activation of Human Macrophages and Tumor-Associated Macrophage Biology. Blood, 119(2): 411-421.

Porta C, Rimoldi M, Raes G, et al., 2009, Tolerance and M2 (Alternative) Macrophage Polarization Are Related Processes Orchestrated by P50 Nuclear Factor KappaB. Proc Natl Acad Sci U S A, 106(35): 14978-14983.

Bonizzi G, Karin M, 2004, The Two NF-KappaB Activation Pathways and Their Role in Innate and Adaptive Immunity. Trends Immunol, 25(6): 280-288.

Lawrence T, Gilroy DW, 2007, Chronic Inflammation: A Failure of Resolution?. Int J Exp Pathol, 88(2): 85-94.

Hagemann T, Lawrence T, McNeish I, et al., 2008, Re-Educating Tumor-Associated Macrophages by Targeting NF-KappaB. J Exp Med 2008, 205(6): 1261-1268.

Tu SP, Jin H, Shi JD, et al., 2012, Curcumin Induces the Differentiation of Myeloid-Derived Suppressor Cells and Inhibits Their Interaction with Cancer Cells and Related Tumor Growth. Cancer Prevention Research, 5(2): 205-215.

Yadav V, Mishra K, Singh D, et al., 2005, Immunomodulatory Effects of Curcumin. Immunopharmacology and Immunotoxicology, 27(3): 485-497.

Zhou Y, Zhang T, Wang X, et al., 2015, Curcumin Modulates Macrophage Polarization Through the Inhibition of the Toll-Like Receptor 4 Expression and Its Signaling Pathways. Cellular Physiology and Biochemistry, 36(2): 631-641.

Chen F, Guo N, Cao G, et al., 2014, Molecular Analysis of Curcumin-Induced Polarization of Murine RAW264.7 Macrophages. Journal of Cardiovascular Pharmacology, 63(6): 544-552.

Lin Y, Xu J, Lan H, 2019, Tumor-Associated Macrophages in Tumor Metastasis: Biological Roles and Clinical Therapeutic Applications. Journal of Hematology & Oncology, 12(1): 76.