학술논문

Newly identified adipose tissue macrophage populations in obesity with distinct chemokine and chemokine receptor expression
Document Type
Academic Journal
Source
International Journal of Obesity. Dec 01, 2010 34(12):1684-1694
Subject
Language
English
ISSN
0307-0565
Abstract
OBJECTIVE:: Infiltration by macrophages is a hallmark of obesity-related adipose tissue (AT) inflammation that is tightly linked to insulin resistance. Although CD11c AT macrophages (ATMs) have recently been shown to promote inflammation in obese mice, the knowledge on phenotype and function of different ATM populations is still very limited. This study aimed at identifying and characterizing ATM populations in obesity. METHODS:: Isolation of ATM populations defined by CD11c and mannose receptor (MR) expression and analysis of gene expression in high-fat diet-induced obese mice. RESULTS:: Obesity provoked a shift from a predominant MRCD11c population (‘MR-ATM’) to two MR populations, namely MRCD11c (‘CD11c-ATM’) and MRCD11c (double negative, ‘DN-ATM’). Although CD11c-ATMs were of a clear inflammatory M1 phenotype, DN-ATMs expressed few inflammatory mediators and highly expressed genes for alternative activation (M2) markers involved in tissue repair, such as arginase and YM1. In contrast, MR-ATMs marginally expressed M1 and M2 markers but highly expressed chemokines, including Mcp-1 (Ccl2) and Mcp-3 (Ccl7). Both CD11c-ATMs and DN-ATMs, but not MR-ATM, highly expressed a panel of chemokine receptors (namely Ccr2, Ccr5, Ccr3 and Cx3cr1), whereas the expression of Ccr7 and Ccr9 was selective for CD11c-ATMs and DN-ATMs, respectively. Notably, stressed adipocytes upregulated various chemokines capable of attracting CD11c-ATM and DN-ATM. CONCLUSION:: This study identifies a novel ATM population with a putatively beneficial role in AT inflammation. This DN-ATM population could be attracted to the obese AT by similar chemokines such as inflammatory CD11c-ATM, on which only Ccr7 is uniquely expressed.