title: Chrysotile asbestos and H2O2 increase permeability of alveolar epithelium.
abstract: The alveolar epithelium contains tight 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 cells, and the generation of reactive oxygen species such as hydrogen peroxide (H2O2). The present study examined changes in transepithelial resistance (Rt) (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 micrograms/cm2 for 24 h. In separate experiments, monolayers were exposed to H2O2 at concentrations of 50, 75, and 100 microM for 1 h Rt was measured using a voltohmmeter. Prior to treatment, monolayers had a high Rt (> 2000 ohms.cm2). Permeability was assessed by measuring flux of [3H]sucrose from apical to basolateral compartments. Cytotoxicity was evaluated by lactate dehydrogenase (LDH) and preincorporated [14C]adenine release. The morphological integrity of the monolayers was evaluated by scanning electron microscopy. Chrysotile asbestos and H2O2 exposure resulted in dose-dependent decrease in alveolar epithelial Rt and increases in permeability under conditions that did not result in over cytotoxicity. These results demonstrate that both chrysotile asbestos and H2O2 have effects on alveolar epithelial Rt and permeability and suggest a potential role for the alveolar epithelium in mediation of asbestos-induced pulmonary interstitial disease.
authors.affiliation: Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Gardner
authors.forename: A R
authors.initials: AR
authors.lastname: Brody
authors.forename: J B
authors.initials: JB
authors.lastname: Mangum
authors.forename: J I
authors.initials: JI
authors.lastname: Everitt
mesh_terms: D000818:Animals; D017632:Asbestos, Serpentine / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D017632:Asbestos, Serpentine; D006861:Hydrogen Peroxide