Table I.
macrophage subpopulations in diseases
| M1 or M2 | Disease Model | Subjects | Key Findings | References |
|---|---|---|---|---|
| M1 | NA | Human macrophages | IFN-γ can activate macrophages by increasing its antigen presenting capacity, pro-inflammatory cytokine production and phagocytosis. | Nathan et al., 1983 [28] |
| M1 | Pneumonia | Mouse | IKKβ suppresses M1 macrophage activation in response to LPS and infection. | Fong et al., 2008 [48] |
| M1 | Obesity, Type 2 diabetes | Human | Endotoxin induces resistin production by macrophages, which contributes to the insulin resistance in type 2 diabetes. | Lehrke et al., 2004 [41] |
| not specified | Liver ischaemia- reperfusion injury | Rat | Simvastatin provide protection against the adverse effects of I/R injury by suppressing TNF-a, LDH, and serum aminotransferase activity (This phenotype is probably related to “M1” cells). | Dibazar et al., 2008 [32] |
| not specified | Experimental cardiac injury | Rat | A subset of macrophages infiltrating necrotic myocardium expresses osteopontin during cardiac injury (This phenotype is probably related to “M1” cells). | Murry et al., 1994 [35] |
| not specified | Obesity | Mouse | Resistin is mainly produced by macrophages in human. It exacerbates adipose inflammation and insulin resistance in mice (This phenotype is probably related to “M1” cells). | Qatanani et al., 2009 [45] |
|
| ||||
| M2 | NA | Mouse | IL-4 enhances macrophage mannose receptor expression and activity. L-4 induces alternative activation of macrophages, characterized by an elevated endocytic capacity of mannosylated ligands, increased MHC-II expression, and reduced proinflammatory cytokine production. | Stein et al., 1992 [30] |
| M2 | Parasite infection | Mouse | IL-4 promotes the uptake and parasite killing activity of macrophages. | Wirth et al., 1989 [31] |
| M2 | NA | Human | IL-4 suppresses the production of superoxide by macrophages. | Abramson and Gallin, 1990 [78] |
| M2 | Obesity, Leishmaniasis infection | Mouse (Mac-PPARγ KO and PPARδ−/− mouse) | PPARγ is required for the alternative activation of macrophages and regulates insulin resistance. | Odegaard et al., 2007 [55] |
| M2 | Obesity | Mouse (PPARδ−/−) | PPARδ regulates the expression of arginase 1, costimulatory molecules, and pattern recognition receptors during the alternative activation of macrophages. | Odegaard et al., 2008 [58] |
| M2 | Atherosclerosis | Human | The activation of PPARγ skews monocytes toward an anti-inflammatory M2 phenotype. | Bouhlel et al., 2007 [57] |
| M2 | NA | Human | M2 enhances regulatory properties of Treg cells by inducing membrane bound TGF-β1. | Savage et al., 2008 [39] |
| M2 | Obesity | Mouse | Adipoctyes and hepatocytes can produce IL-4 and IL-13 cytokines to promote M2 activation and limit inflammation. PPARδ is required for the alternative activation of macrophages. | Kang et al., 2008 [49] |
| not specified | Pneumococcal pneumonia | Mouse | Alveolar macrophages reduce mortality of pneumococcal pneumonia by suppressing polymorphonuclear cells mediated inflammation (This phenotype is probably related to “M2” cells). | Knapp et al., 2003 [36] |
| not specified | Multiple sclerosis | Human | Macophages express a series of anti-inflammatory molecules and are unable to response to inflammatory stimuli after myelin-ingestion (This phenotype is probably related to “M2” cells). | Boven et al., 2006 [37] |
| not specified | NA | Mouse | Macrophages obtain an anti-inflammatory phenotype after S1P or S1P1 receptor-specific agonist treatment (This phenotype is probably related to “M2” cells). | Hughes et al., 2008 [38] |
| not specified | Insulin resistance | Mouse | Deficiency of PPARγ in macrophages results in insulin resistance and poor responses to antidiabetic thiazolidinediones (This phenotype is probably associated with lack of “M2”). | Hevener et al., 2007 [56] |
| not specified | Balloon injury | Rat, Rabbit | Depletion of macrophages by clodronate-containing liposomes decreased neointimal formation after mechanical arterial injury (This phenotype is probably related to “M2” cells). | Danenberg et al., 2002[17] |
| not specified | Hypoxia-induced pulmonary remodeling | Rat, Calve | Precursors of a monocyte/macrophage lineage are essential contributors to hypoxia-induced pulmonary vascular remodeling (This phenotype is probably related to “M2” cells). | Frid et al., 2006 [24] |
| not specified | Wound healing | Mouse (lysM-Cre/DTR transgenic mouse) | Depletion of macrophages severely impaired wound inflammation, angiogenesis and tissue remodeling (This phenotype is probably related to “M2” cells). | Goren et al., 2009 [13] |
| not specified | Ischemic cardiomyopathy | Mouse (MCP-1 transgenic mouse) | Macrophage infiltration facilitates vascularization by proceding the formation of new vessel sprouts and altering the microenvironment (This phenotype is probably related to “M2” cells). | Moldovan et al., 2000 [19] |
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| M1/M2 | Obesity, Air pollution | Mouse | M1/M2 balance is associated with air pollution induced insulin resistance. | Sun et al., 2009 [46] |
| M1/M2 | Obesity, Air pollution | Mouse | When exposed to air pollution, M1/M2 balance is altered and associated with insulin resistance. | Xu et al., 2010 [47] |
| M1/M2 | Hepatic fibrosis | Mouse (CD11b-DTR transgenic mouse), Rat | Macrophages have distinct effect on liver injury and repair. Depletion of macrophages when liver fibrosis reduced scarring, while depletion during recovery led to a failure of matrix degradation. | Duffield, 2010 [25] |
| M1/M2 | NA | Mouse | Both IFN-γ and IL-4 can increase MHC-II on macrophages. | Cao et al., 1989 [29] |
NA, not available