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 alphavbeta5. 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-1alpha 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.
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 alphavbeta5. 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-1alpha 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.
Authors: Michael Spencer; Aiwei Yao-Borengasser; Resat Unal; Neda Rasouli; Catherine M Gurley; Beibei Zhu; Charlotte A Peterson; Philip A Kern Journal: Am J Physiol Endocrinol Metab Date: 2010-09-14 Impact factor: 4.310
Authors: Claudia Macaubas; Khoa D Nguyen; Ariana Peck; Julia Buckingham; Chetan Deshpande; Elizabeth Wong; Heather C Alexander; Sheng-Yung Chang; Ann Begovich; Yue Sun; Jane L Park; Kuang-Hung Pan; Richard Lin; Chih-Jian Lih; Erin M Augustine; Carolyn Phillips; Andreas V Hadjinicolaou; Tzielan Lee; Elizabeth D Mellins Journal: Clin Immunol Date: 2011-12-28 Impact factor: 3.969
Authors: Luis A Zúñiga; Wen-Jun Shen; Barbara Joyce-Shaikh; Ekaterina A Pyatnova; Andrew G Richards; Colin Thom; Sofia M Andrade; Daniel J Cua; Fredric B Kraemer; Eugene C Butcher Journal: J Immunol Date: 2010-10-29 Impact factor: 5.422
Authors: Derek K Hagman; Ilona Larson; Jessica N Kuzma; Gail Cromer; Karen Makar; Katya B Rubinow; Karen E Foster-Schubert; Brian van Yserloo; Peter S Billing; Robert W Landerholm; Matthew Crouthamel; David R Flum; David E Cummings; Mario Kratz Journal: Metabolism Date: 2017-02-02 Impact factor: 8.694