Effect of acute ozone exposure on the proteinase-antiproteinase balance in the rat lung.
Lung disease may result from a persisting proteinase excess or a depletion of antiproteinase in pulmonary parenchyma. We investigated the in vivo effect of a 48-hr exposure to ozone at 0.5, 1.0, or 1.5 ppm on proteinase and antiproteinase activity of rat lungs. Elastase inhibitory capacities of serum, lung tissue, and airway washings were measured as indicators of antielastase activity. Trypsin inhibitory capacity was measured using an esterolytic procedure. Proteinase was measured as radioactive release from a 14C-globin substrate. The 48-hr exposures to O3 at levels up to 1 ppm produced concentration-dependent decreases of 35-80% of antiproteinase activities in serum and in lung tissue. However, exposure to 1.5 ppm O3 resulted in no decrease in antiproteinase activities. Acid proteinase activities (pH 4.2) were increased 65-120% by exposure to 1 or 1.5 ppm O3, which correlated with inflammatory cells noted histologically. At 1.5 ppm O3, pulmonary edema and hemorrhage were noted in histologic sections. These changes led to a flooding of the alveoli with up to 40 times normal protein levels and a greater than fivefold increase in airway antiproteinase. These data suggest that serum and soluble lung tissue antiproteinase activity decreased upon exposure to low levels of ozone. However, if O3 exposure is high enough to produce pulmonary hemorrhage, antiproteinase may increase following serum exudation. These changes may be important in the development of ozone-induced lung diseases, especially emphysema.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000201:enzymology; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D010126:Ozone / Q000633:toxicity*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism*; D051381:Rats; D014361:Trypsin Inhibitors / Q000378:metabolism
D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D010126:Ozone; D004549:Elastin; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase