Witten M L, Grad R, Quan S F, Sobonya R E, Hubbard A K, Lantz R C, Lentz L A, Devine L C, Lemen R J
Department of Physiology, University of Arizona Health Sciences Center, Tucson 85724.
Exp Lung Res. 1990 Jul-Aug;16(4):339-53. doi: 10.3109/01902149009108849.
We studied the effects of acute smoke exposure on lung permeability, eicosanoids, and inflammatory cell activity. Thirty-five New Zealand white rabbits were anesthetized, paralyzed, and exposed to 60 tidal volume breaths of diesel fuel-polycarbonate plastic smoke or sham smoke within 10 min. At 1 h postexposure the rabbits were killed and their lungs were removed for bronchoalveolar lavage (BAL) or pathologic procedures. Smoke exposure caused decreases in technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, mol. wt. 492 Da) biological half-life (t1/2), BAL plasminogen activator, and BAL leukotriene B4 (LTB4). In addition, alveolar macrophage acid phosphatase enzyme activity increased in smoke-exposed rabbits. The leukotriene synthesis inhibitor, piriprost (U-60,257), given before smoke exposure, caused attenuation of the changes in 99mTcDTPA uptake and plasminogen activator, swelling of type I alveolar cell epithelium, a large increase in lung inflammatory cells, and decreases in BAL LTB4, prostaglandin E2 (PGE2), and TxB2 (stable metabolite of thromboxane, TxA2). We conclude that changes in alveolar-capillary barrier permeability and plasminogen activator activity occur within 1 h after exposure to smoke and may play an early role in the inflammatory process associated with smoke inhalation injury. Furthermore, piriprost attenuates the smoke-induced increase in alveolar-capillary barrier permeability and decrease in plasminogen activator activity and causes a swelling of type I alveolar epithelium. However, our data suggest that neither lung eicosanoids or the alveolar macrophage lysis process plays a major role in the smoke-induced increase in alveolar-capillary barrier permeability.
我们研究了急性烟雾暴露对肺通透性、类花生酸和炎症细胞活性的影响。35只新西兰白兔被麻醉、麻痹，并在10分钟内接受60次潮气量的柴油-聚碳酸酯塑料烟雾或假烟雾暴露。暴露后1小时处死兔子，取出肺进行支气管肺泡灌洗（BAL）或病理检查。烟雾暴露导致锝标记的二乙三胺五乙酸（99mTcDTPA，分子量492 Da）生物半衰期（t1/2）、BAL纤溶酶原激活剂和BAL白三烯B4（LTB4）降低。此外，烟雾暴露的兔子肺泡巨噬细胞酸性磷酸酶活性增加。在烟雾暴露前给予白三烯合成抑制剂吡嘧司特（U-60,257），可减轻99mTcDTPA摄取和纤溶酶原激活剂的变化、I型肺泡上皮细胞肿胀、肺炎症细胞大量增加，以及BAL中LTB4、前列腺素E2（PGE2）和TxB2（血栓素TxA2的稳定代谢产物）降低。我们得出结论，暴露于烟雾后1小时内肺泡-毛细血管屏障通透性和纤溶酶原激活剂活性发生变化，可能在与烟雾吸入性损伤相关的炎症过程中起早期作用。此外，吡嘧司特可减轻烟雾诱导的肺泡-毛细血管屏障通透性增加和纤溶酶原激活剂活性降低，并导致I型肺泡上皮肿胀。然而，我们的数据表明，肺类花生酸或肺泡巨噬细胞溶解过程在烟雾诱导的肺泡-毛细血管屏障通透性增加中均不起主要作用。
