PhospholipaseCγ1/calcium-dependent membranous localization of Gsdmd-N drives endothelial pyroptosis, contributing to lipopolysaccharide-induced fatal outcome

作者：Hong Liu, Da Tang, Xiaoyu Zhou, Xiaoping Yang, Alex F. Chen · 发表于：American Journal of Physiology-Heart and Circulatory Physiology · 年份：2020 · DOI：10.1152/ajpheart.00731.2019 · 被引用次数：31 · 研究领域：Inflammasome and immune disorders、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Heme Oxygenase-1 and Carbon Monoxide

Our study newly reveals that phospholipase Cγ1 (PLCγ1) contributes to gasdermin D (Gsdmd)-mediated endothelial pyroptosis in a calcium-dependent fashion. Cytosolic calcium signaling promotes activated NH 2 -terminal fragment of Gsdmd (Gsdmd-N) to translocate to the plasma membrane, enhancing endothelial pyroptosis induced by cytoplasmic LPS. Genetic or pharmacologic inhibition of endothelial PLCγ1 attenuated breakdown of endothelial barrier, reduced vascular leakage, improve perfusion disturbances, and decrease mortality of mice in endotoxemia.