Abstract
Resolvin E1 (RvE1) is an endogenous lipid mediator derived from the ω‐3 polyunsaturated fatty acid eicosapentaenoic acid that displays potent pro‐resolving actions in experimental models of inflammation. However, little is known about the impact of RvE1 on neutrophil apoptosis, a critical control point in the resolution of inflammation. Culture of human neutrophils with RvE1 did not affect neutrophil longevity, RvE1 accelerated apoptosis evoked by phagocytosis of opsonized Escherichia coli or yeast. RvE1 through the leukotriene B4 receptor BLT1 enhanced ROS generation by NADPH oxidase, leading to subsequent activation of caspase‐8 and caspase‐3. Moreover, RvE1 mitigated phagocytosis‐induced ERK activation. RvE1 also attenuated myeloperoxidase (through Mac‐1), serum amyloid A (through the formyl peptide receptor 2) and bacterial DNA (through TLR9)‐evoked concurrent ERK and phosphatidylinositol 3‐kinase/Akt‐mediated apoptosis‐suppressing signals. These led to reductions in the expression of the antiapoptotic protein Mcl‐1, collapse of mitochondrial transmembrane potential and activation of caspase‐3. Our results identify a novel BLT1 receptor‐mediated mechanism, promotion of phagocytosis‐induced neutrophil apoptosis by which RvE1 could enhance neutrophil apoptosis and subsequently promote inflammation resolution. (Grant support: CIHR MOP‐97742).
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