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
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DOI：
10.1038/sj.ijo.0803632
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发表时间：
2007-09-01
影响因子：
4.9
通讯作者：
Stulnig, T. M.
中科院分区：
文献类型：
--
作者：
Zeyda, M.;Farmer, D.;Stulnig, T. M.
目的：肥胖与慢性低度炎症和脂肪组织中巨噬细胞丰度增加有关。脂肪组织巨噬细胞（ATM）被认为是干扰脂肪细胞的功能，导致胰岛素抵抗，从而有助于2型糖尿病的发病机制。巨噬细胞存在于不同类型的分化中，但ATMs的性质在很大程度上是未知的。设计和测量：基质血管细胞（SVC）和ATMs从来自不同位置的人脂肪组织中分离。我们通过流式细胞术、内吞试验和分泌细胞因子的测定来表征ATM的表型和功能。为了比较，我们使用的“经典”（M1）和“替代”，抗炎（M2）类型分化在体外从外周血monocytes.Results：原型M2巨噬细胞，ATM表达了大量的甘露糖受体，血红蛋白清道夫受体CD 163和整合素α v β 5。表达这些分子的细胞数量与供体的体重指数（BMI）显著相关。值得注意的是，对常见的单核细胞/巨噬细胞标志物CD 14呈阳性的SVC含有相当大部分的血液单核细胞，其丰度与BMI无关，这表明需要在此鉴定的表面标志物来鉴定ATM。ATM表现出与M2巨噬细胞相似的内吞活性，因此分泌大量的IL-10和IL-1受体拮抗剂。然而，ATM中促炎介质TNF-α、IL-6、IL-1、MCP-1和MIP-1 α的基础和诱导分泌甚至高于促炎M1巨噬细胞。ATM包含特定的巨噬细胞类型，其通过表面标志物表达是M2样的，但它们能够产生大量的炎性细胞因子，这可能大大有助于胰岛素抵抗的发展。
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 alpha v beta 5. 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-alpha, IL-6, IL-1, MCP-1 and MIP-1 alpha was even higher in ATMs than in pro-inflammatory 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.