Acid contact in the rodent pulmonary alveolus causes proinflammatory signaling by membrane pore formation.

American Journal of Physiology. Lung Cellular and Molecular Physiology
Kristin WestphalenJahar Bhattacharya

Abstract

Although gastric acid aspiration causes rapid lung inflammation and acute lung injury, the initiating mechanisms are not known. To determine alveolar epithelial responses to acid, we viewed live alveoli of the isolated lung by fluorescence microscopy, then we microinjected the alveoli with HCl at pH of 1.5. The microinjection caused an immediate but transient formation of molecule-scale pores in the apical alveolar membrane, resulting in loss of cytosolic dye. However, the membrane rapidly resealed. There was no cell damage and no further dye loss despite continuous HCl injection. Concomitantly, reactive oxygen species (ROS) increased in the adjacent perialveolar microvascular endothelium in a Ca(2+)-dependent manner. By contrast, ROS did not increase in wild-type mice in which we gave intra-alveolar injections of polyethylene glycol (PEG)-catalase, in mice overexpressing alveolar catalase, or in mice lacking functional NADPH oxidase (Nox2). Together, our findings indicate the presence of an unusual proinflammatory mechanism in which alveolar contact with acid caused membrane pore formation. The effect, although transient, was nevertheless sufficient to induce Ca(2+) entry and Nox2-dependent H(2)O(2) release from the alveolar e...Continue Reading

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Citations

Mar 26, 2015·BMC Anesthesiology·Torsten RichterThea Koch
May 14, 2016·Seminars in Immunopathology·Jahar Bhattacharya, Kristin Westphalen
Feb 13, 2018·The Journal of Clinical Investigation·Jaime L HookJahar Bhattacharya
Jan 8, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xiaofei CongXiaoli Zhao
Jun 6, 2018·Pulmonary Circulation·Rebecca F HoughJahar Bhattacharya
Sep 21, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jun YinWolfgang M Kuebler
Nov 9, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Dolly MehtaWolfgang M Kuebler
Sep 17, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Susanne HeroldIstván Vadász
Jun 28, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jurjan AmanVictor W M van Hinsbergh
Apr 10, 2018·Clinical Hemorheology and Microcirculation·Johannes GramattéTorsten Richter
Feb 8, 2019·JCI Insight·Rebecca F HoughJahar Bhattacharya

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