Murray PJ, Wynn TAObstacles and opportunities for understanding macrophage polarization. J Leukoc Biol 89: 557-563

Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Pl., Memphis, TN 38105, USA.
Journal of leukocyte biology (Impact Factor: 4.29). 03/2011; 89(4):557-63. DOI: 10.1189/jlb.0710409
Source: PubMed


Macrophages are now routinely categorized into phenotypic subtypes based on gene expression induced in response to cytokine and pathogen-derived stimulation. In the broadest division, macrophages are described as being CAMs (M1 macrophages) or AAMs (M2 macrophages) based on their exposure to TLR and IFN signals or Th2 cytokines, respectively. Despite the prolific use of this simple classification scheme, little is known about the precise functions of effector molecules produced by AAMs, especially how representative the CAM and AAM subtypes are of tissue macrophages in homeostasis, infection, or tissue repair and how plasticity in gene expression regulates macrophage function in vivo. Furthermore, correlations between mouse and human tissue macrophages and their representative subtypes are lacking and are a major barrier to understanding human immunity. Here, we briefly summarize current features of macrophage polarization and discuss the roles of various macrophage subpopulations and macrophage-associated genes in health and disease.

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    • "Further subtypes of macrophage/microglia exist, including the predominantly proinflammatory M1 cell (iNOS+) which secretes cytokines including TNF-í µí»¼ and IL-1í µí»½ and the M2 cell (Arg1+), which is anti-inflammatory in nature and is associated with the secretion of IL-10 [175] [176] [177]. Unique stimuli endow macrophages/microglia with their phenotype and effector function. "
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    ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE). MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease.
    Full-text · Article · Oct 2014
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    • "Different subtype macrophages are involved in the inflammatory micro-environment, including classically activated macrophages (M1 macrophages), which mediate host defense and antitumor immunity; alternatively activated macrophages (M2 macrophages), which suppress inflammatory responses and promote wound healing; tumor-associated macrophages (TAM), which suppress tumor immunity; the monocytic subset of myeloid-derived suppressor cells (MDSCs, which are functionally similar to TAMs) and regulatory macrophages, which predominantly secrete IL-10, and many other different cytokines, play differential roles in viral infection and tumor formation. Although there are some differences among the M2, TAM, MDSC and regulatory subsets of macrophages, each of these populations has a predominant immunosuppressive activity [13]. However, under the liver micro-environment, the role of HCV core protein interaction with macrophages remains largely unclear. "
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    ABSTRACT: Background The core protein of hepatitis C virus (HCV) is found in the cytoplasm and nuclei of infected cells, including hepatocytes and other cells in the liver. The core protein could be secreted as well. Resident liver macrophages are dependent on the tissue micro-environment and external stimuli to differentiate M1 and M2 hypotypes with distinct functions, and increased expression of the nuclear transcription factor STAT3 was seen in M2-polarized macrophages. In contrast to proinflammatory M1 macrophages, M2 macrophages serve beneficial roles in chronic inflammation, immunosuppression, and tumorigenesis. Methods Monocyte-derived human macrophage line (mTHP-1) was treated with the exogenous HCV core protein. Next, the mTHP-1 culture supernatant or cell pellets were added to culture media of normal human liver cell line (L02). Results Only the culture supernatant stimulated L02 cells proliferation, which was associated with phosphorylated ERK expression. Core protein activated mTHP-1 cells showed enhanced pro- and anti-inflammatory cytokines secretion, which was accompanied by high expression of phosphorylated NF-κB105 and NF-κB65. However, phosphorylated STAT1, and STAT3, which are normally associated with M1 and M2 macrophage polarization, and cell surface expression of CD206, CD14, CD16, and CD86, were unaltered. A transwell co-culture system showed that only in mTHP-1 co-cultured with L02 in the presence of exogenous core protein, were higher levels of phosphorylated STAT3 and CD206 seen. Conclusions We showed L02 cells proliferation was accelerated by the culture supernatant of mTHP-1 cells treated with the exogenous HCV core protein. The exogenous core protein mediated the interaction between macrophages and hepatocytes in co-culture, which enhanced the expression of phosphorylated STAT3 and CD206 in macrophages.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "Neutrophils contribute to the initial defense against foreign microbes and their ultimate removal (resolution) is essential for optimal tissue repair (Martin and Feng, 2009; Novoa and Figueras, 2012). Macrophages, comprising distinct subpopulations of M1 or M2 subtypes, secrete growth factors and cytokines that may attract keratinocytes and fibroblasts to trigger either tissue repair or scar formation (Leibovich and Ross, 1975; Serhan and Savill, 2005; Sica and Mantovani, 2012; Murray and Wynn, 2011). Neutrophils and macrophages can have pro-or anti-repair effects after injury, depending on the tissue and injury context (Dovi et al., 2003; Brancato and Albina, 2011; Marrazzo et al., 2011; Walters et al., 2009). "
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    ABSTRACT: Neutrophils and macrophages, as key mediators of inflammation, have defined functionally important roles in mammalian tissue repair. Although recent evidence suggests that similar cells exist in zebrafish and also migrate to sites of injury in larvae, whether these cells are functionally important for wound healing or regeneration in adult zebrafish is unknown. To begin to address these questions, we first tracked neutrophils (lyzC(+), mpo(+)) and macrophages (mpeg1(+)) in adult zebrafish following amputation of the tail fin, and detailed a migratory timecourse that revealed conserved elements of the inflammatory cell response with mammals. Next, we used transgenic zebrafish in which we could selectively ablate macrophages, which allowed us to investigate whether macrophages were required for tail fin regeneration. We identified stage-dependent functional roles of macrophages in mediating fin tissue outgrowth and bony ray patterning, in part through modulating levels of blastema proliferation. Moreover, we also sought to detail molecular regulators of inflammation in adult zebrafish and identified Wnt/β-catenin as a signaling pathway that regulates the injury microenvironment, inflammatory cell migration and macrophage phenotype. These results provide a cellular and molecular link between components of the inflammation response and regeneration in adult zebrafish.
    Full-text · Article · Jul 2014 · Development
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