![]() ![]() Macrophages are heterogeneous populations composed of phenotypically and functionally distinct subsets that have differential roles in inflammatory processes and require specific tissue milieu for their differentiation and maintenance ( 1– 7). This study has revealed a mechanism by which lipid metabolites control macrophage activation and function, modification of which could lead to a new therapeutic approach for MS and other inflammatory disorders. In addition, G2A-deficient rats showed an ameliorated EAE and an inhibited autoimmune response. M1 polarization could be inhibited by a G2A neutralizing Ab, which led to an inhibited disease in rat EAE. This process was directed by the G2A receptor, which was only found in differentiated M1 or monocytes from MS patients. The effects of Lp-PLA 2 on M1 function were mediated by lysophosphatidylcholine, a bioactive product of oxidized lipids hydrolyzed by Lp-PLA 2 through JAK2-independent activation of STAT5 and upregulation of IRF5. Specific inhibition of Lp-PLA 2 led to an ameliorated EAE via markedly decreased inflammatory and demyelinating property of M1. In this study, we describe that lipoprotein-associated phospholipase A 2 (Lp-PLA 2) plays an important role in controlling inflammatory macrophage (M1) polarization in rodent experimental autoimmune encephalomyelitis (EAE) and in monocytes from multiple sclerosis (MS) patients. Macrophage polarization is a dynamic and integral process in tissue inflammation and remodeling. ![]()
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