[Changes of alveolar macrophage plasminogen activator in rats exposed to nitrogen dioxide]

In order to clarify the role of nitrogen dioxide (NO2) in the development of lung injury, male Wistar rats were exposed continuously to 0.3 or 5.0 ppm NO2 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 NO2 exposure. Throughout the whole test period, the largest number was obtained in the group exposed to 5.0 ppm, followed by the group exposed to 0.3 ppm, and then by the control group. 2) The plasminogen activator (PA) released from alveolar macrophages was increased dose-dependently by NO2 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 NO2 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 5.0 ppm NO2, total protein in the lavage fluid increased, and the elastase inhibitory capacity (EIC) per milligram of protein decreased. In the group exposed to 0.3 ppm NO2, 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 0.3 ppm NO2. 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 NO2. For the detection of the effect of NO2 on the lung tissue, PA appears to be a more sensitive indicator than EIC.