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Co‐culture of alveolar epithelial and endothelial cells blunts failure of alveolar barrier function in hypoxia
Author(s) -
Zuegel Stefanie,
Bartsch Peter,
Mairbaurl Heimo
Publication year - 2008
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.22.1_supplement.932.8
Subject(s) - alveolar epithelium , hypoxia (environmental) , chemistry , permeability (electromagnetism) , barrier function , lung , albumin , reabsorption , vascular permeability , medicine , endocrinology , microbiology and biotechnology , biology , oxygen , biochemistry , membrane , sodium , organic chemistry
Alveolar hypoxia increases alveolar barrier permeability and inhibits reabsorption favoring formation of pulmonary edema. Monocultures of primary rat alveolar type II cells (ATII) and rat lung microvascular endothelial cells (EC) are commonly used models. We designed a co‐culture (CC) system of EC and ATII on nucleopore filters to study mechanisms of hypoxia (1.5% O2, 24 h) induced failure of alveolar barrier function. CC showed a 40% higher resistance and a higher short‐circuit current (ISC) in normoxia and hypoxia than ATII monolayers. In normoxia, Na/K‐ATPase capacity was higher in CC than in ATII, but ENaC activity was comparable. Hypoxia inhibited ISC (−40%), Na/K‐ATPase (−25%) and ENaC (−25%) only in ATII but not in CC. In normoxia, Na‐fluorescein permeability was lowest in CC. It was 9x higher in ATII and 120x higher in EC than in CC. Hypoxia increased fluorescein‐permeability in ATII (+55%) and in CC (+400%) but not in EC alone. FITC‐albumin‐permeability in normoxia was 35x higher in EC than in ATII and in CC. Hypoxia increased albumin‐permeability only in ATII (+35%). These findings indicate that the interaction between alveolar epithelial and endothelial cells tightens the alveolar barrier and increases trans‐alveolar Na‐transport activity. Hypoxia‐effects on permeability and ion transport are less pronounced in the co‐culture than in monocultures of alveolar epithelial cells.