Ozone-induced augmentation of eicosanoid metabolism in epithelial cells from bovine trachea.
Epithelial injury and inflammation have been implicated in ozone-induced airway hyperresponsiveness. Because ozone is relatively insoluble and highly reactive, toxicologic effects of this compound may be limited to the plasma membranes of airway epithelium. We hypothesize that oxidant damage to epithelium may result in elaboration of various eicosanoids, which are known to alter airway smooth muscle responsiveness and epithelial cell functions (including ion transport). To examine eicosanoid metabolism after exposure to 0.1 to 10.0 ppm ozone, epithelial cells derived from bovine trachea were isolated and grown to confluency. Bovine tracheal cells in culture expressed differentiated features characteristic of epithelial cells, including a plasma membrane with a specialized polar morphology, an extensive network of filaments that were connected through intercellular junctional complexes, and keratin-containing monofilaments as determined by indirect immunofluorescent localization. Monolayers were alternately exposed to ozone and culture medium for 2 h in a specially designed in vitro chamber using a rotating inclined platform. Eicosanoid products were measured by the release of [3H]-labeled products from cells incubated with [3H]-arachidonic acid for 24 h before exposure and by the release of immunoreactive products into the cell supernatant. Both methods revealed ozone-induced increases in cyclooxygenase and lipoxygenase product formation with significant increases in prostaglandins E2, F2 alpha, 6-keto F1 alpha, and leukotriene B4. Release rates of immunoreactive products were dose-dependent, and ozone concentrations as low as 0.1 ppm produced an increase in prostaglandin F2 alpha. These findings are consistent with the hypothesis that ozone can augment eicosanoid metabolism in airway epithelial cells.
Leikauf
G D
GD
Institute of Environmental Medicine, New York University Medical Center, Tuxedo.
Driscoll
K E
KE
Wey
H E
HE
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004537:Eicosanoic Acids / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D010126:Ozone / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D010126:Ozone