Alternative activation of macrophages

Gordon, Siamon

doi:10.1038/nri978

Cited by 5,417 publications

(5,438 citation statements)

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“…[8][9][10][11] Therefore, adipose tissue macrophages are assumed to critically contribute to the pathogenesis of type 2 diabetes mellitus and the metabolic syndrome by driving obesity-associated chronic inflammation. In contrast, adipose tissue macrophages may also have cytoprotective anti-inflammatory properties, as identified by the expression of several markers that determine an alternatively activated, anti-inflammatory macrophage type, 12,13 for instance, the hemoglobin scavenger receptor CD163. 10,14 CD163 is exclusively expressed on monocytes and macrophages and mediates endocytosis of haptoglobinhemoglobin complexes, 15 thereby preventing oxidative and nitrosative toxicity emerging upon red blood cell hemolysis.…”

Section: Introductionmentioning

confidence: 99%

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

et al. 2009

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Objective: Insulin resistance in visceral obesity is substantially driven by adipose tissue inflammation, particularly by macrophages accumulating in obese adipose tissue. In contrast, adipose tissue macrophages express the hemoglobin scavenger receptor (CD163) and heme oxygenase-1 (gene: HMOX1) that together protect from oxidative stress. Our aim was to evaluate the expression of CD163 and HMOX1 in intra-abdominal visceral (omental) and subcutaneous adipose tissue as well as circulating soluble CD163 concentrations in human obesity and its association with adipose tissue inflammation, body fat distribution and insulin resistance. Methods: CD163, HMOX1 and CD68 mRNA expression in visceral and subcutaneous adipose tissue, serum concentration of soluble CD163 in morbidly obese patients (body mass index (BMI) 440 kg m À2 ), who underwent laparoscopic surgery for gastric banding (n ¼ 20), matched for age and sex to controls (BMIo30 kg m À2 ; n ¼ 20) was analyzed. Results: CD163 expression was highly upregulated in human adipose tissue and soluble CD163 serum concentration was elevated in obese vs lean subjects. HMOX1 was upregulated in adipose tissue by obesity as well and expressed predominantly in macrophages. Although CD163 expression strictly correlated with macrophage abundance, HMOX1 was additionally upregulated within macrophages. This upregulation was significantly lower in visceral compared with subcutaneous adipose tissue. Strikingly, relative visceral adipose tissue expression of HMOX1 negatively correlated with waist-to-hip ratio and the homeostasis model assessment of insulin resistance (both P ¼ 0.024). Conclusions: Visceral obesity is associated with defective upregulation of heme oxygenase-1 in visceral adipose tissue. A lack of this antioxidative and anti-inflammatory enzyme in visceral adipose tissue could contribute to the development of insulin resistance.

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Section: Introductionmentioning

confidence: 99%

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

et al. 2009

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“…As a secondary outcome of this study, human M2 macrophages were for the first time thoroughly analyzed regarding surface protein expression thus corroborating other studies mainly investigating gene expression and/or murine cells. 11,12,16,29,30 Surface marker characteristics of ATMs are important not only for their quantification but also for their isolation to be used in in vitro experiments, for example, to investigate the cellular source of adipokines and chemokines. 27,31 So far, only CD31 and CD45 have been shown to be expressed on the surface of human CD14 pos cells derived from the AT.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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: 99%

“…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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Innate Immunity

Coligan¹,

Vogel

2006

CP in Immunology

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CHAPTER 14 Innate ImmunityINTRODUCTION M any different cell types of the innate immune system can recognize pathogens and tumor cells, and it is their quick response that constitutes the first line of defense against infectious agents and malignant transformation. Innate immunity against microbes and tumors can be initiated and/or executed by macrophages, dendritic cells, NK cells, NKT cells and others. The biological consequences of pathogen recognition by these cell types is elimination of the pathogen and the induction of expression of costimulatory molecules, cytokines, and chemokines that facilitate development of the adaptive immune response. In addition, macrophages and dendritic cells can internalize apoptotic cells and cellular debris, as well as pathogenic organisms, and in this fashion, eliminate cellular waste and noxious agents.At this time, Chapter 14 remains a chapter in transition, in which new protocols for the analysis of the innate immune response will be combined with updated protocols currently presented at other locations in earlier versions of Current Protocols in Immunology. Complement will continue to keep its own place in this series (see Chapter 13), but NK cells will gradually be introduced into Chapter 14. UNITS 14.1-14.9 contain protocols for studying macrophages (detailed below). A commentary unit on the receptors and ligands involved in NK cell recognition is now included in this chapter (UNIT 14.10). A commentary section on signaling through NK receptors (UNIT 11.9B) can be found in Chapter 11. Protocols on isolating mouse (UNIT 3.22) and human (UNIT 7.7) NK cells are provided elsewhere, and assays for measuring cytotoxic NK cell function can be found in UNIT 7.18. UNIT 14.11 provides protocols for isolating and functional analysis of human NKT cells. UNIT 14.13 describes basic methods for the characterization, quantification, and functional analysis of murine invariant NKT (iNKT) cells in vivo or in vitro. These cells recognize CD1d-restricted lipid antigens and have immunoregulatory properties. Human and mouse CD1d restricted glycolipid antigen(s) and the iNKT cell functions they elicit are highly conserved and, hence, mouse is an excellent animal model for understanding iNKT cell biology in vivo. Protocols on other cell types that form integral parts of the innate immune system, such as neutrophils (UNIT 7.23) and dendritic cells (UNITS 3.7 & 7.32) are also presented elsewhere. A primary means of pathogen recognition by cells of the innate immune response is via Toll-like receptors (TLR). TLRs recognize biochemical molecular patterns that are characteristic of microbial structural components, e.g., Tolllike receptor 9 (TLR9) recognizes CpG DNA that is characteristic of bacterial DNA. A commentary unit (UNIT 14.12) describes the known TLRs. Eventually, after updating, many of the outlying units will be brought together in this chapter.Macrophages originate in the bone marrow from stem cells that are thought to give rise to a bipotent granulocyte/macrophage progenitor popu...

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Alternative activation of macrophages

Cited by 5,417 publications

References 122 publications

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

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

Innate Immunity

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