PhospholipaseCγ1/calcium-dependent membranous localization of Gsdmd-N drives endothelial pyroptosis, contributing to lipopolysaccharide-induced fatal outcome
Hong Liu, Da Tang, Xiaoyu Zhou, Xiaoping Yang, Alex F. Chen
Abstract
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.
Topics & Concepts
PyroptosisLipopolysaccharideCalciumMedicineInflammationChemistryCell biologyImmunologyBiologyInternal medicineInflammasomeInflammasome and immune disordersNeutrophil, Myeloperoxidase and Oxidative MechanismsHeme Oxygenase-1 and Carbon Monoxide