title: The effects of chronic sidestream cigarette smoke exposure on eicosanoid production by tracheal epithelium.
abstract: Environmental exposure to sidestream cigarette smoke (SSCS) has been associated with an increased incidence of pulmonary infection and bronchospasm. Chronic exposure to SSCS could modify the release of bronchoreactive eicosanoids by tracheal epithelium, the site of initial contact by lung with inhaled toxins. To assess this possibility, New Zealand white rabbits were placed in an environmental chamber flushed with 3 L of SSCS, 15 min/day for 20 days. Eighteen hours after the last exposure the animals were sacrificed and the tracheas were explanted. At 7 days, the epithelial cell outgrowths were exposed to media containing endotoxin (10 micrograms/mL) or acrolein (50 microM), an aldehyde commonly found in smoke, or to control media. After a 2-h exposure, media were assayed for eicosanoids by radioimmunoassay. PGE2 was produced in epithelium from normal animals (5.7 +/- 1.3 ng/10(6) cells), and was not significantly different in SSCS-exposed epithelium. When incubated in medium containing acrolein, PGE2 production increased significantly in SSCS-exposed epithelium (14.9 +/- 2.5, p < .05) but not in control groups. Endotoxin also increased PGE2 production in SSCS-exposed cells (12.6 +/- 3.3 ng/10(6), p < .05). Baseline production of 6-keto PGF1 alpha was 10.8 +/- 3.2 ng/10(6) cells in non-SSCS controls and did not change significantly in these cells with the addition of endotoxin or acrolein. In acrolein plus SSCS-exposed cells, 6-keto PGF1 alpha increased, in a dose-dependent manner, to 88.1 +/- 26.1 ng/10(6) (p < .05 compared to all normals, SSCS-exposed controls, and SSCS plus LPS). TxB2 release in control, non-SSCS-exposed cells was 13.3 +/- 2.8 ng/10(6) cells and was significantly increased (P < .05) only in the SSCS plus acrolein group (60.7 +/- 16.2 ng/10(6) cells). The results indicate that even brief, recurrent exposure to SSCS can change the production of cyclooxygenase products, particularly PGE2, 6- keto PGF1 alpha, and TxB2. This may reflect an altered ability of SSCS-exposed tracheal epithelium to respond to environmental (e.g., acrolein) or bacterial (e.g., endotoxin) insults.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Joseph
authors.forename: M L
authors.initials: ML
authors.lastname: Witten
authors.forename: C H
authors.initials: CH
authors.lastname: Burke
authors.forename: C A
authors.initials: CA
authors.lastname: Hales
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000171:Acrolein / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015289:Leukotrienes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D011863:Radioimmunoassay; D013931:Thromboxanes / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014132:Trachea / Q000166:cytology*
chemical_list: D015777:Eicosanoids; D015289:Leukotrienes; D008070:Lipopolysaccharides; D013931:Thromboxanes; D014028:Tobacco Smoke Pollution; D015121:6-Ketoprostaglandin F1 alpha; D000171:Acrolein; D015232:Dinoprostone