Chrysotile asbestos and H2O2 increase permeability of alveolar epithelium

Our plain-English summary of Chrysotile asbestos and H2O2 increase permeability of alveolar epithelium, by S.Y. Gardner, A.R. Brody, J.B. Mangum, et al (Experimental Lung Research, 1997).

The study

• Authors: S.Y. Gardner, A.R. Brody, J.B. Mangum, J.I. Everitt
• Journal: Experimental Lung Research
• Published: 1997;23(1):1-16
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This was a laboratory study on cells, not on people. The authors isolated alveolar type II cells from the lungs of 6-week-old male rats and grew them on porous filters into cell layers meant to model the lining of the lung's air sacs. They exposed the layers to chrysotile asbestos at 5, 10 and 25 micrograms per square centimeter for 24 hours, or to latex beads at the same amounts as a comparison particle. In separate experiments they used hydrogen peroxide, a reactive oxygen chemical, at 50, 75 and 100 micromolar for 1 hour. Chrysotile caused a dose-dependent fall in the layers' electrical resistance, a measure of barrier tightness, and a dose-dependent rise in permeability to radiolabeled sucrose. Latex beads had no effect on permeability. Hydrogen peroxide had similar effects. These changes occurred without detectable cytotoxicity on two tests, LDH release and radiolabeled adenine release; the authors described this as subtle injury. In preliminary experiments, 150 to 250 micromolar hydrogen peroxide was cytotoxic. The authors concluded that this increased permeability may link events in the air sacs to later interstitial lung disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment using cultured rat lung cells as a model of the alveolar barrier
• Who was studied: Alveolar type II cells isolated from 6-week-old male CD rats, grown as monolayers on porous filters and used on day 3 or 4 of culture. The work was done at the Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA. The number of rats is not stated.
• Exposure: Chrysotile asbestos (Plastibest-20, from the National Institute of Environmental Health Sciences) at 5, 10 and 25 micrograms per square centimeter for 24 hours. Latex beads at the same concentrations served as control particles. In separate experiments, hydrogen peroxide was given at 50, 75 and 100 micromolar for 1 hour.
• Main results:
  • Chrysotile asbestos at 5, 10 and 25 micrograms per square centimeter for 24 hours produced a dose-dependent decrease in the transepithelial resistance of the cell layers. Exact values appear only in a figure that is unreadable in the scan.
  • Permeability of the cell layers to radiolabeled sucrose increased in a dose-dependent way after asbestos treatment, while latex beads had no effect.
  • The asbestos-related changes occurred without cytotoxicity, as measured by LDH release and radiolabeled adenine release.
  • The authors described the asbestos-induced permeability increase as occurring after subtle injury, meaning without cytotoxicity, and without inflammatory cells present.
  • Scanning electron microscopy showed that the cells had taken up asbestos and latex particles without appreciable changes in their structure.
  • Hydrogen peroxide at 50, 75 and 100 micromolar for 1 hour produced a dose-dependent decrease in transepithelial resistance.
  • Permeability of the cell layers increased in a dose-dependent way after hydrogen peroxide treatment, without cytotoxicity at these concentrations.
  • In preliminary experiments (data not shown), hydrogen peroxide at 150 to 250 micromolar also lowered resistance, but these concentrations were cytotoxic.
• The authors' conclusion: The authors concluded that chrysotile asbestos directly decreased resistance and increased permeability of alveolar epithelium without cytotoxicity, and that this was not a nonspecific particle effect. They found that hydrogen peroxide had similar effects. They suggested this increase in permeability may serve as a link between particle and inflammatory-cell interactions in the air sacs and the later development of interstitial lung disease.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Epithelium, Asbestos Exposure, Reactive Oxygen Species (ROS), Lactate Dehydrogenase (LDH), Scanning Electron Microscopy (SEM), Interstitial.

Related studies

• Asbestos-induced lung epithelial permeability: potential role of nonoxidant pathways — M.W. Peterson, J. Kirschbaum (1998)
• In vitro biodegradation of chrysotile fibres by alveolar macrophages and mesothelial cells in culture: comparison with a pH effect — M.C. Jaurand, A. Gaudichet, et al. (1984)
• Chrysotile asbestos causes AEC apoptosis via the caspase activation in vitro and in vivo — T. Kido, Y. Morimoto, et al. (2008)
• Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals — A. Aljandali, H. Pollack, et al. (2001)
• The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro — K. Donaldson, J. Slight, et al. (1988)
• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)

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