Acrolein stimulates eicosanoid release from bovine airway epithelial cells.
Injury to the airway mucosa after exposure to environmental irritants is associated with pulmonary inflammation and bronchial hyperresponsiveness. To better understand the relationships between mediator release and airway epithelial cell injury during irritant exposures, we studied the effects of acrolein, a low-molecular-weight aldehyde found in cigarette smoke, on arachidonic acid metabolism in cultured bovine tracheal epithelial cells. Confluent airway epithelial cell monolayers, prelabeled with [3H]arachidonic acid, released significant levels of 3H activity when exposed (20 min) to 100 microM acrolein. [3H]arachidonic acid products were resolved using reverse-phase high-performance liquid chromatography. Under control conditions the released 3H activity coeluted predominantly with the cyclooxygenase product, prostaglandin (PG) E2. After exposure to acrolein, significant "peaks" in 3H activity coeluted with the lipoxygenase products 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE, as well as with PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. Dose-response relationships for acrolein-induced release of immunoreactive PGF2 alpha and PGE2 from unlabeled epithelial monolayers demonstrated 30 microM acrolein as the threshold dose, with 100 microM acrolein inducing nearly a fivefold increase in both PGF2 alpha and PGE2. Cellular viability after exposure to 100 microM acrolein, determined by released lactate dehydrogenase activity, was not affected until exposure periods were greater than or equal to 2 h. These results implicate the airway epithelial cell as a possible source of eicosanoids after exposure to acrolein.
Doupnik
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CA
Department of Environmental Health, University of Cincinnati College of Medicine, Ohio 45267-0182.
Leikauf
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GD
D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015777:Eicosanoids / Q000302:isolation & purification / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D011865:Radioisotope Dilution Technique; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D001095:Arachidonic Acids; D015777:Eicosanoids; D014316:Tritium; D000171:Acrolein