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Alveolar Acid Injury Causes Endothelial Mitochondrial Depolarization
Author(s) -
Hough Rebecca F,
Gusarova Galina A,
Islam Mohammad N,
Bhattacharya Jahar
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.982.5
Subject(s) - chemistry , calcein , pulmonary alveolus , mitochondrion , endothelium , alveolar epithelium , lung , pathology , biochemistry , medicine , membrane , macrophage , in vitro
Lung inflammation and edema, the characteristic features of Acute Lung Injury (ALI), result from lung microvascular barrier deterioration. Since ALI associates with loss of mitochondrial function, we evaluated endothelial mitochondrial responses to alveolar acid instillation. We established isolated, blood‐perfused mouse lungs at constant pulmonary artery, left atrial and alveolar pressures (n=4). To view alveoli and capillaries by confocal microscopy, we micropunctured alveoli to load the cytosolic fluorescent dyes, calcein green (CG) and calcein red (CR), respectively. We loaded capillaries with the mitochondrial potentiometric dye, trimethylrhodamine ethyl ester (TMRE). To establish acid‐induced alveolar injury, we microinjected alveoli with concentrated hydrochloric acid (HCl). HCl decreased CG by 75±4% from baseline (p<0.05, mean±SE), indicating that alveolar acid instillation injured the epithelial plasma membrane. Concomitantly, TMRE, but not CR fluorescence decreased (p<0.05), indicating that despite lack of membrane injury endothelial mitochondria were depolarized. Alveolar PBS injection was without effect. Since loss of calcein dye is an indicator of plasma membrane injury, we interpret alveolar contact with concentrated acid caused membrane injury to epithelium, but not endothelium. Nevertheless, endothelial mitochondria were depolarized and possibly dysfunctional after alveolar acid injection. We suggest, acid‐induced alveolar injury abrogates endothelial bioenergetics, leading to the microvascular deterioration underlying ALI (HL105323, HL57556). Support or Funding Information HL105323, HL57556