Chrysotile asbestos and H2O2 increase permeability of alveolar epithelium

The alveolar epithelium contains light junctions and provides a barrier to passage of potentially injurious substances into the pulmonary interstitium. Alveolar epithelial injury is hypothesized to be an important early event in the pathogenesis of asbestosis. Mechanisms that may contribute to alveolar epithelial cell injury following asbestos exposure include the physicochemical interactions between asbestos fibers and cell, and the generation of reactive oxygen species such as hydrogen peroxide (H2O2). The present study examined changes in transepithelial resistance (R(t)) (a measure of barrier function) and permeability of alveolar epithelium after chrysotile asbestos and H2O2 exposure. Alveolar epithelial cell monolayers, obtained from isolation of rat alveolar type II cells and grown on porous supports, were exposed to chrysotile asbestos or polystyrene beads (control) at concentrations of 5, 10, and 25 mu g/cm(2) for 24 h. In separate experiments, monolayers were exposed to H2O2 at concentrations of 50, 75, and 100 mu M for 1 h. R(t) was measured using a voltohmmeler. Prior to treatment, monolayers had a high R(t) (>2000 ohms . cm(2)). Permeability was assessed by measuring flux of [H-3] sucrose from apical to basolateral compartments. Cytotoxicity was evaluated by lactate dehydrogenase (LDH) and preincorporated [C-14]adenine release. The morphological integrity of the monolayers was evaluated by scanning electron microscopy. Chrysotile asbestos and H2O2 exposure resulted in dose-dependent decreases in alveolar epithelial R(t) and increases in permeability under conditions that did not result in overt cytotoxicity. These results demonstrate that both chrysotile asbestos and H2O2 have effects on alveolar epithelial R(t) and permeability and suggest a potential role for the alveolar epithelium in mediation of asbestos-induced pulmonary interstitial disease.