CHRYSOTILE ASBESTOS AND H2O2 INCREASE PERMEABILITY OF ALVEOLAR EPITHELIUM

The alveolar epithelium contains light junctions and provides a barrie r to passage of potentially injurious substances into the pulmonary in terstitium. Alveolar epithelial injury is hypothesized to be an import ant early event in the pathogenesis of asbestosis. Mechanisms that may contribute to alveolar epithelial cell injury following asbestos expo sure include the physicochemical interactions between asbestos fibers and cell, and the generation of reactive oxygen species such as hydrog en peroxide (H2O2). The present study examined changes in transepithel ial resistance (R(t)) (a measure of barrier function) and permeability of alveolar epithelium after chrysotile asbestos and H2O2 exposure. A lveolar epithelial cell monolayers, obtained from isolation of rat alv eolar type II cells and grown on porous supports, were exposed to chry sotile asbestos or polystyrene beads (control) at concentrations of 5, 10, and 25 mu g/cm(2) for 24 h. In separate experiments, monolayers w ere 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, monolayer s had a high R(t) (>2000 ohms . cm(2)). Permeability was assessed by m easuring flux of [H-3] sucrose from apical to basolateral compartments . Cytotoxicity was evaluated by lactate dehydrogenase (LDH) and preinc orporated [C-14]adenine release. The morphological integrity of tile m onolayers was evaluated by scanning electron microscopy. Chrysotile as bestos and H2O2 exposure resulted in dose-dependent decreases in alveo lar epithelial R(t) and increases in permeability under conditions tha t 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 e pithelium in mediation of asbestos-induced pulmonary interstitial dise ase.