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Alterations in alveolar epithelial tight junctions induced by chronic ethanol ingestion
Author(s) -
Koval Michael,
Fernandez Alberto L,
Joshi Pratibha C,
Guidot David M
Publication year - 2006
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.20.4.a751-c
Subject(s) - tight junction , paracellular transport , claudin , occludin , barrier function , ards , cell junction , alveolar epithelium , lung , chemistry , endocrinology , medicine , microbiology and biotechnology , biology , permeability (electromagnetism) , biochemistry , cell , membrane
Chronic alcohol abuse increases the risk of the acute respiratory distress syndrome (ARDS) nearly four‐fold. In animals, chronic ethanol ingestion alters alveolar barrier function by increasing paracellular leak. This suggests that chronic ethanol ingestion might alter alveolar tight junction protein expression. To test this, rats were fed an isocaloric liquid diet containing either ethanol or a maltin‐dextrin control for 6 wks and then whole lungs were isolated and examined for changes in tight junction protein expression. By immunoblot, whole lungs of ethanol‐fed rats had increased expression of the tight junction proteins claudin‐4 and claudin‐5. In contrast, claudin‐3 expression was decreased in the whole lungs of ethanol‐fed rats as compared to controls. Thus, there were relative changes in the whole lung claudin expression profile, which correlated with increased epithelial permeability, as opposed to a net decrease in claudin expression. Consistent with deficient lung barrier function, alveolar epithelial cells (AECs) isolated and cultured from ethanol‐fed rats also had increased paracellular leak as compared to AECs from control‐fed animals. By immunofluorescence, this difference in permeability correlated with changes in tight junction protein localization, where AECs isolated from ethanol‐fed rats had prominent intracellular vesicles containing claudins, occludin and ZO‐1 as compared to control AECs where these proteins were mainly localized to the plasma membrane. Thus, chronic ethanol ingestion may enhance alveolar leak by altering tight junction assembly and/or remodeling which, in turn, could influence the steady state level of claudins present in tight junctions.