Ozone Inactivation of Human α\u3csub\u3e1\u3c/sub\u3e-Proteinase Inhibitor

Ozone decreased the trypsin, chymotrypsin, and elastase inhibitory activities of human α1-proteinase inhibitor (α1-PI) both in plasma and in solutions of the pure inhibitor. The total loss of porcine elastase inhibitory activity required 18 mol of ozone/mol of pure α1-PI and approximately 850 mol of ozone/mol of α1-PI in plasma. A corresponding loss of the ability to inhibit human leukocyte elastase was observed. Inactivated α1-PI contains four residues of methionine sulfoxide, in addition to oxidized tyrosine and tryptophan. Electrophoretic analysis demonstrated that the ozone-inactivated α1-PI did not form normal complexes with serine proteinases. These findings suggest that the inhalation of ozone could inactivate α1-PI on the airspace side of the lung to create a localized α1-PI deficiency, which might contribute to the development of emphysema