NO₂ Decreases Paracellular Resistance to Ion and Solute Flow in Alveolar Epithelial Monolayers

Abstract

Primary cultured monolayers of rat alveolar epithelial cells grown on tissue culture-treated Nuclepore filters were exposed to 2.5 ppm nitrogen dioxide (NO₂) for 2-20 min. Changes in monolayer bioelectric properties and solute permeabilities were subsequently measured. Exposure to NO₂ produced a dose-dependent decrease in monolayer transepithelial electrical resistance (R), whereas monolayer short-circuit current was unaffected. Post-exposure monolayer permeability to ¹⁴C-sucrose (which primarily crosses alveolar epithelium via the paracellular pathway) increased markedly. That for “H-glycerol (which permeates through both paracellular and transcellular pathways) increased to a lesser extent. Partial recovery of K, and solute permeabilities was noted by 48-h post-exposure. The time courses of the decrease in R, and increase in solute permeabilities were similar. These results suggest that N0₂ primarily impairs passive alveolar epithelial barrier functions in vitro, probably by altering intercellular junctions, and does not appear to directly affect cell membrane active ion transport processes. When correlated with results obtained from experimental approaches, studies of in vitro alveolar epithelial monolayers may facilitate investigations of dosimetry, sites, and mechanisms of oxidant injury in the lung.