[Changes of procoagulant and fibrinolytic activities in the alveoli of rats exposed to ozone].
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.
Shima
M
M
Department of Public Health, School of Medicine, Chiba University.
Adachi
M
M
D000818:Animals; D001779:Blood Coagulation Factors / Q000187:drug effects*; D005342:Fibrinolysis / Q000187:drug effects*; D008264:Macrophages; D008297:Male; D010126:Ozone / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains
D001779:Blood Coagulation Factors; C045072:macrophage procoagulant activity; D010126:Ozone