In order to clarify the role of nitrogen dioxide (NO
2) in the development of lung injury, male Wistar rats were exposed continuously to 0.3 or 5.0ppm NO
2 for 10, 20, 30, 60 and 90 days, and alveolar macrophages and lavage fluid obtained by bronchoalveolar lavage were examined. The results were as follows:
1) The number of alveolar macrophages increased significantly in response to NO
2 exposure. Throughout the whole test period, the largest number was obtained in the group exposed to 5.0ppm, followed by the group exposed to 0.3ppm, and then by the control group.
2) The plasminogen activator (PA) released from alveolar macrophages was increased dosedependently by NO
2 exposure. The activities were significantly high in the groups exposed for 10 to 20 days at each concentration, and then slightly decreased at 30 days. Thereafter, activity showed a tendency to increase, reaching the maximum level on the 60th day of exposure.
3) Similarly, the fibrinolytic activity in the lavage fluid was increased dose-dependently by NO
2 exposure. The maximum activity was noted on the 10th day of exposure, followed by a rapid decrease up to the 30th day, and a slight rise again between the 60th and 90th day.
4) In the group exposed to 5.0ppm NO
2, total protein in the lavage fluid increased, and the elastase inhibitory capacity (EIC) per milligram of protein decreased. In the group exposed to 0.3ppm NO
2, however, no difference from the control group was noted.
These results revealed that the alveolar macrophages were affected and increased PA activity as a result of exposure to as little as 0.3ppm NO
2. This was shown to result in an increase of the fibrinolytic activity in the alveoli, leading to damage to the lung tissue. This evidence may explain the morphological findings of the appearance of emphysematous change in the lungs of rats exposed to low levels of NO
2. For the detection of the effect of NO
2 on the lung tissue, PA appears to be a more sensitive indicator than EIC.
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