Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes

Mantovani, Alberto; Sozzani, Silvano; Locati, Massimo; Allavena, Paola; Sica, Antonio

doi:10.1016/s1471-4906(02)02302-5

Cited by 4,723 publications

(4,456 citation statements)

References 65 publications

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“…11 According to a widely used classification, we refer to classically IFN-g/LPS-activated macrophages as M1 and alternatively activated macrophages, which can be induced by IL-4 and IL-13 as M2. 12 Also IL-10 induces M2 macrophages, but these cells clearly differ from prototypic M2 macrophages activated by IL-4 or IL-13. 11,12 Importantly, M1 and M2 are regarded as only two extremes of a continuum of functional stages of macrophages.…”

Section: Introductionmentioning

confidence: 95%

“…12 Also IL-10 induces M2 macrophages, but these cells clearly differ from prototypic M2 macrophages activated by IL-4 or IL-13. 11,12 Importantly, M1 and M2 are regarded as only two extremes of a continuum of functional stages of macrophages. 11,12 M2 macrophages appear to play a role in tissue repair and parasite defence, 13,14 but exert poor anti-bacterial killing activity.…”

Section: Introductionmentioning

confidence: 95%

“…11,12 Importantly, M1 and M2 are regarded as only two extremes of a continuum of functional stages of macrophages. 11,12 M2 macrophages appear to play a role in tissue repair and parasite defence, 13,14 but exert poor anti-bacterial killing activity. 15 The molecular repertoire of M2 macrophages includes proteins that are expressed at very low levels by classically activated macrophages (M1) including the IL-1 receptor antagonist (IL-1Ra), IL-10 and the mannose receptor (MR) that is involved in the uptake of mannose-containing particles.…”

Section: Introductionmentioning

confidence: 99%

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Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

et al. 2007

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Objective: Obesity is associated with a chronic low-grade inflammation and an increased abundance of macrophages in adipose tissue. Adipose tissue macrophages (ATMs) are assumed to interfere with adipocyte function leading to insulin resistance, thereby contributing to the pathogenesis of type 2 diabetes mellitus. Macrophages exist in separate types of differentiation, but the nature of ATMs is largely unknown. Design and measurements: Stromal vascular cells (SVCs) and ATMs were isolated from human adipose tissues from different locations. We characterized ATMs phenotypically and functionally by flow cytometry, endocytosis assay and determination of secreted cytokines. For comparison, we used macrophages of the 'classical' (M1) and the 'alternative', anti-inflammatory (M2) type differentiated in vitro from peripheral blood monocytes. Results: Like prototypic M2 macrophages, ATMs expressed considerable amounts of mannose receptor, haemoglobin scavenger receptor CD163 and integrin avb5. The number of cells expressing these molecules correlated significantly with the donors' body mass indices (BMIs). Notably, SVCs positive for the common monocyte/macrophage marker CD14 contained a considerable fraction of blood monocytes, the abundance of which did not correlate with the BMIs, pointing to the requirement of the surface markers identified here for the identification of ATMs. ATMs showed endocytic activities similar to M2 macrophages and accordingly secreted high amounts of IL-10 and IL-1 receptor antagonist. However, basal and induced secretion of pro-inflammatory mediators TNF-a, IL-6, IL-1, MCP-1 and MIP-1a was even higher in ATMs than in proinflammatory M1 macrophages. Conclusion: ATMs comprise a particular macrophage type that is M2-like by surface marker expression, but they are competent to produce extensive amounts of inflammatory cytokines, which could considerably contribute to the development of insulin resistance.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

et al. 2007

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“…Although several studies have suggested that AAMΦs enhance Th2 cell differentiation [28,29], more recent in vivo findings indicate that in the context of helminth infection, AAMΦs are not essential for the development of Th2-type responses. Following S. mansoni infection, LysM Cre IL-4Rα − /flox mice showed Th2-type cytokine responses similar to controls, although IL-4Rα − /− mice exhibited marked reductions in Th2-type cytokines [2].…”

Section: Control Of Inflammationmentioning

confidence: 99%

Alternatively activated macrophages in helminth infections

Kreider

Anthony

Urban

et al. 2007

Current Opinion in Immunology

318

270

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“…In organ transplantation, inflammatory Ly6C hi monocytes infiltrate the allograft early after transplantation and differentiate into suppressive Ly6C lo macrophages following costimulatory blockade (5). Therefore, the signals that dictate macrophage polarization towards alternatively activated Ly6C lo /M2 control immunological tolerance (10, 11). …”

Section: Introductionmentioning

confidence: 99%

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Braza

Conde

Garcia

et al. 2018

American Journal of Transplantation

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Summary The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.

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Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes

Cited by 4,723 publications

References 65 publications

Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

Alternatively activated macrophages in helminth infections

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

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