INACTIVATION OF ALPHA1-PROTEINASE INHIBITOR AND BRONCHIAL MUCOUS PROTEINASE INHIBITOR BY CIGARETTE SMOKE IN VITRO AND IN VIVO

Aqueous solutions of unfractionated cigarette smoke suppress complex formation between human alpha1-proteinase inhibitor (α1Pi) and elastase in vitro. Oxidizing agents reproduce the effect of smoke, while anti-oxidants prevent it. Inhalation of cigarette smoke in rats causes a significant decrease in functional activity of rat lung α1Pi in vivo, which can be restored by treatment with reducing agents. Human bronchial mucous proteinase inhibitor (BMPi) is also inactivated by cigarette smoke and oxidants in vitro. Functional activity of BMPi obtained from human smokers is 20% lower than that from nonsmokers. Oxidation of proteinase inhibitors leading to their functional depression in the lung might constitute a major biochemical link between cigarette smoking and chronic obstructive lung disease in man.