Joseph P M, Witten M L, Burke C H, Hales C A
Department of Medicine, Massachusetts General Hospital, Boston 02114, USA.
Exp Lung Res. 1996 May-Jun;22(3):317-35. doi: 10.3109/01902149609031778.
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.
环境暴露于侧流香烟烟雾（SSCS）与肺部感染和支气管痉挛的发病率增加有关。长期暴露于SSCS可能会改变气管上皮细胞释放支气管反应性类花生酸，气管上皮是肺部与吸入毒素最初接触的部位。为了评估这种可能性，将新西兰白兔置于一个用3升SSCS冲洗的环境舱中，每天15分钟，共20天。最后一次暴露18小时后，处死动物并取出气管。在第7天，将上皮细胞生长物暴露于含有内毒素（10微克/毫升）或丙烯醛（50微摩尔）的培养基中，丙烯醛是烟雾中常见的一种醛，或暴露于对照培养基中。暴露2小时后，通过放射免疫分析法检测培养基中的类花生酸。正常动物的上皮细胞产生前列腺素E2（PGE2）（5.7±1.3纳克/10⁶个细胞），暴露于SSCS的上皮细胞中PGE2的产生没有显著差异。当在含有丙烯醛的培养基中孵育时，暴露于SSCS的上皮细胞中PGE2的产生显著增加（14.9±2.5，p<0.05），而对照组没有增加。内毒素也增加了暴露于SSCS的细胞中PGE2的产生（12.6±3.3纳克/10⁶个细胞，p<0.05）。非SSCS对照组中6-酮前列腺素F1α（6-keto PGF1α）的基础产量为10.8±3.2纳克/10⁶个细胞，添加内毒素或丙烯醛后这些细胞中的该产量没有显著变化。在丙烯醛加SSCS暴露的细胞中，6-keto PGF1α以剂量依赖的方式增加到88.1±26.1纳克/10⁶个细胞（与所有正常组、暴露于SSCS的对照组以及SSCS加脂多糖组相比，p<0.05）。对照的、未暴露于SSCS的细胞中血栓素B2（TxB2）的释放量为13.3±2.8纳克/10⁶个细胞，仅在SSCS加丙烯醛组中显著增加（P<0.05）（60.7±1,6.2纳克/10⁶个细胞）。结果表明，即使是短暂的、反复暴露于SSCS也会改变环氧化酶产物的产生，特别是PGE2、6-keto PGF1α和TxB2。这可能反映了暴露于SSCS的气管上皮细胞对环境（如丙烯醛）或细菌（如内毒素）损伤的反应能力发生了改变。
