Tight monolayers of rat alveolar epithelial cells: bioelectric properties and active sodium transport

Abstract

Because the pulmonary alveolar epithelium separates air spaces from a fluid-filled compartment, it is expected that this barrier would be highly resistant to the flow of solutes and water. Investigation of alveolar epithelial resistance has been limited due to the complex anatomy of adult mammalian lung. Previous efforts to study isolated alveolar epithelium cultured on porous substrata yielded leaky monolayers. In this study, alveolar epithelial cells isolated from rat lungs and grown on tissue culture-treated Nucleopore filters resulted in tight monolayers with transepithelial resistance greater than 2,000 omega.cm2. Changes in bioelectric properties of these alveolar epithelial monolayers in response to ouabain, amiloride, and terbutaline are consistent with active sodium transport across a polarized barrier. 22Na flux measurements under short-circuit conditions directly confirm net transepithelial absorption of sodium by alveolar epithelial cells in the apical to basolateral direction, comparable to the observed short-circuit current (4.37 microA/cm2). The transport properties of these tight monolayers may be representative of the characteristics of the mammalian alveolar epithelial barrier in vivo.

Developmental Pathways and Specification of Intrapulmonary Stem Cells

“…Similar to observations in vivo, isolated AT2 cells in primary culture lose their phenotypic hallmarks and gradually acquire the morphologic features of AT1 cells (97,98). The cells increasingly express all available AT1 cell phenotypic markers suggesting that AT2 cells in vitro transdifferentiate toward an AT1 cell phenotype (AT1-like cells) (99 -101).…”

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

“…1). The alveolar membrane acts as a semi-permeable barrier due to the presence of tight junctions (5) and the presence of drug transporter proteins (6). This results in ELF concentrations that may be several folds lower or higher than the corresponding plasma concentration, as was nicely summarized by Kiem et al (7) and Rodvold et al (8).…”

Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary oedema

“…Up-regulation of alveolar fluid transport secondary to increased sodium transport by alveolar epithelial cells has been demonstrated in isolated type II alveolar cells, 16,17 isolated lungs ex vivo, 18,19 and in a number of alveolar flooding models induced either by liquid instillation [1][2][3] or by acute lung injury using hyperoxia, 20 endotoxin or bacterial pneumonia. 21,22 Further, ouabain, a specific inhibitor of Na + K + -ATPase, depresses sodium 18,19 and liquid 4,19,23 transport in isolated lungs.…”