Modulation of bronchial epithelial cell barrier function by in vitro ozone exposure.
The epithelial cells lining the small, peripheral airways function as important targets for the action of inspired ozone. Loss of epithelial barrier integrity in these regions is a common element in ozone-induced airway inflammation. To investigate the direct effect of ozone on epithelial barrier function, canine bronchial epithelial (CBE) cells grown with an air interface were exposed for 3 hr to 0.2, 0.5, or 0.8 ppm ozone or to air. Mannitol flux, used as an index of paracellular permeability, increased above air controls by 461%, 774%, and 1172% at the three ozone concentrations, respectively. Transcellular electrical resistance exhibited a dose-related decrease. The immediate effect of 0.8 ppm ozone on permeability was significantly inhibited by preincubation for 48 hr in the presence of 1 ng/ml vitamin E (33%) or 1 microM vitamin A (34%). Responses to 0.5 ppm or 0.8 ppm were inhibited by pretreatment of the cells with 0.1 microM of the actin polymerizing agent phalloidin (34% and 25% inhibition, respectively). The increases in permeability induced by 0.2 and 0.5 ppm ozone were attenuated by 54% and 22%, respectively, at 18 hr after exposure, whereas that to 0.8 ppm was further enhanced by 42% at this time. The effects of ozone are modulated by the availability of antioxidants to the cells and appear to be associated with cytoskeletal dysfunction in CBE cells. The data are consistent with a loss of barrier function linked to a direct oxidative effect of ozone on individual CBE cells and indicate that the reversible or progressive nature of this effect is dose dependent.
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Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205.
Takahashi
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Croxton
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Spannhake
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D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000008:administration & dosage / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005453:Fluorescence; D008353:Mannitol / Q000008:administration & dosage / Q000378:metabolism; D010126:Ozone / Q000493:pharmacokinetics / Q000494:pharmacology*; D010590:Phalloidine / Q000008:administration & dosage / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000378:metabolism
D014801:Vitamin A; D014810:Vitamin E; D010590:Phalloidine; D003571:Cytochalasin B; D008353:Mannitol; D010126:Ozone