Normal human IgG attenuates intracellular superoxide level and permeability in human aortic endothelial cells (HAECs)

Abstract

BackgroundThe protective role of normal human IgG, a circulating antibody, in vascular endothelial cells is not poorly understood. The purpose of this study was to investigate our hypothesis that IgG attenuates intracellular superoxide (O2−) levels and permeability in HAECs via activation of AMPK.ResultsIgG significantly decreased the intracellular O2− levels and endothelial permeability. NADPH oxidase activity and Rac1 activity were attenuated by IgG, which may lead to the decreased O2− formation. In addition, IgG increased MnSOD expression and eNOS Ser1177 phosphorylation contributing to IgG‐induced decrease in O2− level. Notably, IgG activated AMPK as evidenced by increased phosphorylation of AMPK (pAMPK). Interestingly, suppression of AMPK activity by an AMPK inhibitor (AI) abolished IgG‐induced decreases in O2− levels, endothelial permeability, stress fiber formation, and cell migration, suggesting that the protective effects of IgG on HAECs are mediated by AMPK activation. The mechanistic investigation further revealed that inhibition of AMPK prevented IgG‐induced decreases in Rac1 and NADPH oxidase activities and IgG‐induced increases in MnSOD expression and eNOS activity.ConclusionIgG may protect HAECs by attenuating O2− levels by activation of AMPK and subsequent downregulation of NADPH oxidase activity and upregulation of MnSOD expression and eNOS activity.