Document Detail


Acid contact in the rodent pulmonary alveolus causes proinflammatory signaling by membrane pore formation.
MedLine Citation:
PMID:  22561462     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 epithelium. These responses identify alveolar H(2)O(2) release as the signaling mechanism responsible for lung inflammation induced by acid and suggest that intra-alveolar PEG-catalase might be therapeutic in acid-induced lung injury.
Authors:
Kristin Westphalen; Eiji Monma; Mohammad N Islam; Jahar Bhattacharya
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-04
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  303     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-16     Completed Date:  2012-09-20     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L107-16     Citation Subset:  IM    
Affiliation:
Lung Biology Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium Signaling
Cell Membrane / metabolism*,  pathology
Edema / metabolism
Epithelium / enzymology,  immunology,  pathology
Fluoresceins / metabolism
Fluorescent Dyes / metabolism
Fura-2 / metabolism
Gastric Acid
Hydrochloric Acid
Hydrogen Peroxide / metabolism
Inflammation Mediators / metabolism*
Macrophages / pathology,  physiology
Membrane Glycoproteins / genetics,  metabolism,  physiology
Mice
Mice, Knockout
Microvessels / metabolism
NADPH Oxidase / genetics,  metabolism,  physiology
Pneumonia, Aspiration / chemically induced,  immunology,  metabolism
Porosity
Pulmonary Alveoli / blood supply,  immunology,  metabolism*,  pathology
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
HL-36024/HL/NHLBI NIH HHS; HL-64896/HL/NHLBI NIH HHS; HL-69514/HL/NHLBI NIH HHS; HL-78645/HL/NHLBI NIH HHS; R01 HL078645/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fluoresceins; 0/Fluorescent Dyes; 0/Inflammation Mediators; 0/Membrane Glycoproteins; 7647-01-0/Hydrochloric Acid; 7722-84-1/Hydrogen Peroxide; 85138-49-4/2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; 96314-98-6/Fura-2; EC 1.6.3.1/Cybb protein, mouse; EC 1.6.3.1/NADPH Oxidase
Comments/Corrections

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