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 MR+CD11câ» population ('MR-ATM') to two MRâ» populations, namely MRâ»CD11c+ ('CD11c-ATM') and MRâ»CD11câ» (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.
Subject(s)
Adipose Tissue/pathology , Chemokines/metabolism , Insulin Resistance/physiology , Macrophages/metabolism , Obesity/pathology , Receptors, Chemokine/metabolism , Adipocytes , Animals , Cell Separation , Cells, Cultured , Chemokines/genetics , Flow Cytometry , Gene Expression , Immunohistochemistry , Insulin Resistance/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/genetics , Panniculitis/pathologyABSTRACT
The feasibility of using negative ion chemistry to mitigate stratospheric ozone depletion by chlorine-containing radicals, as proposed recently, is addressed here. Previous in situ measurements of the negative ion composition of the stratosphere show that chlorine-containing ions represent only a small fraction of total ions. New measurements of the negative ion temporal evolution in the stratosphere show that the fractional abundance of chlorine-containing ions is never greater than 1 percent at any time in the ion evolution. On the basis of these and other arguments, using negative ion chemistry to mitigate ozone depletion by chlorine-containing compounds is not feasible.