Nitrogen dioxide exposure and alveolar macrophage elastase in hamsters

Adult male hamsters were exposed to 30 +/- 5 ppm nitrogen dioxide (NO2) for periods as long as 30 days. Alveolar macrophages obtained by lung lavage at 0, 2, 5, 14, and 30 days of exposure were present in increased amounts, with the greatest increase 8 times the control amount at 14 days of NO2 exposure. No elastolytic activity was observed in the cell-free lavage fluid. Alveolar macrophages were cultured in serum-free medium for 1 to 6 days. The mediums were collected and assayed for elastolytic activity using Sepharose-coupled [3H] soluble elastin as substrate. Elastolytic activity in the secretions increased significantly at days 2 and 5 but was greatest after 14 days of NO2 exposure. These observations indicate that the secretions of alveolar macrophages from hamsters exposed to NO2 increased elastolytic activity. This activity correlates with the duration of NO2 exposure for periods as long as 14 days. The increased elastolysis observed appears to be dependent on increased numbers of macrophages rather than on increased elastolytic secretion per cell. Inhibition studies with a battery of elastase inhibitors indicated that the elastase(s) secreted from NO2 and control alveolar macrophages have identical properties. The response of hamster macrophage elastase to inhibitors differs from that observed in the mouse and in humans in that it is not inhibited by EDTA, human serum or 1,10-phenanthroline.