Shima M, Adachi M
Department of Public Health, School of Medicine, Chiba University.
Nihon Eiseigaku Zasshi. 1991 Jun;46(2):724-33. doi: 10.1265/jjh.46.724.
The purpose of this study was to evaluate the role of ozone, a reactive product of environmental photochemical oxidation, in the development of pulmonary fibrosis. Male Wistar rats were exposed continuously to 0.5 ppm ozone for 1,4,7 and 14 days, and alveolar macrophages and lavage fluid obtained by bronchoalveolar lavage were examined. The results were as follows: 1) The total protein content in the lavage fluid was significantly increased compared to the control at 1 to 7 days by ozone exposure. Both alveolar macrophage and neutrophil counts increased in response to ozone exposure. However, approximately 90% of the free cells recovered were alveolar macrophages throughout the exposure period. 2) The plasminogen activator (PA) activity released from alveolar macrophages did not change in the group exposed for 1 day. But the activities were significantly high in the groups exposed for 4 to 14 days. 3) The PA activity of the lavage fluid showed a marked increase on the 1st day of ozone exposure, and subsequently decreased rapidly. However, the significantly increased activity was maintained throughout the exposure period. 4) In contrast, the procoagulant (PC) activity was unchanged on the 1st day of ozone exposure but the activity increased significantly on the 4th day, and was maintained at a high level until the 14th day. 5) The elastase inhibitory capacity (EIC) of the lavage fluid was significantly increased compared to the control by ozone exposure, but this difference was not seen throughout the exposure period when the EIC was corrected for the total protein content in the lavage fluid. These results revealed that both PA and PC activities increased in the alveolar fluid of rats exposed to 0.5 ppm ozone. The transition in the respective activities suggested that the fibrinolytic pathway in the alveoli was enhanced early in the exposure to ozone, while the coagulation pathway was enhanced later. This imbalance in coagulation homeostasis may be important in the regulation of fibrotic responses in the lungs of rats exposed to ozone. These findings are in agreement with morphological reports indicating that ozone exposure initially damaged the alveoli and later caused pulmonary fibrosis.
本研究的目的是评估环境光化学氧化的活性产物臭氧在肺纤维化发展过程中的作用。将雄性Wistar大鼠连续暴露于0.5 ppm臭氧中1天、4天、7天和14天，然后对通过支气管肺泡灌洗获得的肺泡巨噬细胞和灌洗液进行检测。结果如下：1）与对照组相比，暴露于臭氧1至7天时，灌洗液中的总蛋白含量显著增加。臭氧暴露后，肺泡巨噬细胞和中性粒细胞计数均增加。然而，在整个暴露期间，回收的游离细胞中约90%是肺泡巨噬细胞。2）暴露1天的组中，肺泡巨噬细胞释放的纤溶酶原激活物（PA）活性没有变化。但在暴露4至14天的组中，该活性显著升高。3）灌洗液的PA活性在臭氧暴露第1天显著增加，随后迅速下降。然而，在整个暴露期间，该活性一直维持在显著升高的水平。4）相比之下，促凝剂（PC）活性在臭氧暴露第1天没有变化，但在第4天显著增加，并一直维持在高水平直至第14天。5）与对照组相比，臭氧暴露使灌洗液的弹性蛋白酶抑制能力（EIC）显著增加，但在校正灌洗液中的总蛋白含量后，在整个暴露期间未观察到这种差异。这些结果表明，暴露于0.5 ppm臭氧的大鼠肺泡液中PA和PC活性均增加。各自活性的转变表明，在暴露于臭氧的早期，肺泡中的纤维蛋白溶解途径增强，而凝血途径在后期增强。这种凝血稳态的失衡可能在暴露于臭氧的大鼠肺部纤维化反应的调节中起重要作用。这些发现与形态学报告一致，表明臭氧暴露最初会损伤肺泡，随后导致肺纤维化。
