Oxidant Effects on Rat and Human Lung Proteinase Inhibitors

摘要

The activity of alpha-1-proteinase inhibitor (alpha-PI) in lung lavage fluids was measured by elastase inhibition and the immunological concentration by enzyme-linked immunoassay. The inhibitor's functional activity was defined as active: immunological concentration. In rats chronically exposed to 10 ppm nitrogen dioxide (NO2) or diesel emissions (3.5 mg/cu m particulates), only diesel exposures caused a decrease in functional activity. In rats chronically exposed to NO2 (0.5 ppm background with peaks of 1.5 ppm) or ozone (O3)(0.06 ppm background with peaks of 0.25 ppm), functional activity and immunological concentration were unchanged. In other protocols, rats were exposed acutely to 0.8 ppm or 1.2 ppm O3, or to 0.5 ppm or 0.8 ppm O3 with 8 percent carbon dioxide. Functional activity was not reduced, but immunological concentration and elastase inhibitory activity were increased in relation to the total amount of O3 inhaled. The functional activity of alpha1-PI also was measured in the bronchoalveolar lavage fluids of humans acutely exposed to NO2 (0.05 ppm with 2 ppm peaks, or to 1.5 ppm continuously) or to O3 (0.4 ppm) during exercise. Functional activity and immunological concentrations were unchanged. Bronchial leukocyte proteinase inhibitor (BLPI) was looked for but was not found in the rat. In nasal lavage fluids from humans acutely exposed to 0.4 ppm O3, functional activity of BLPI decreased immediately after exposure, but was unchanged 18 hours later. The immunological concentration was unchanged in the study and in bronchoalveolar lavage fluids from individuals exposed to NO2. Human mast cell tryptase was measured in nasal and bronchoalveolar lavage fluids from subjects exposed acutely to 0.4 ppm O3 with exercise. Tryptase was elevated in the nasal fluids immediately and 18 hours after exposure, and in 8 of 9 bronchoalveolar lavage fluid samples obtained 18 hours after exposure.