Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity.

Abstract

The elastase inhibitory capacity per milligram .alpha.1-proteinase inhibitor (.alpha.1PI) was measured in the bronchoalveolar lavage (BAL) fluid from 26 healthy smokers and 24 nonsmokers. Activity was decreased by 40% in smokers'' BAL fluid compared to nonsmokers. This effect was demonstrated by using human neutrophil elastase and porcine pancreatic elastase as test enzyme elastase, EC 3.4.21.11, and was reproducible when selected individuals in each group underwent lavage on repeated occasions. The functional activity of .alpha.1-antichymotrypsin was not decreased in smokers'' BAL fluid. Crossed antigen-antibody electrophoresis confirmed that inactivation of .alpha.1PI was responsible for the decrease in the elastase inhibitory capacity of smokers'' BAL fluid. .alpha.1PI purified from smokers'' BAL fluids contained methionine sulfoxide (4 mol/mol of inactive .alpha.1PI); .alpha.1PI from nonsmokers'' BAL fluid did not. Smokers'' .alpha.1PI was indistinguishable from nonsmokers'' .alpha.1PI on the basis of electrophoretic mobility, MW and immunoreactivity. Thus oxidation of methionine residues in lung .alpha.1PI was associated with cigarette smoking. Because chemical oxidation of .alpha.1PI in vitro caused loss of its elastase inhibitory activity, methionine oxidation may also be the cause of decreased functional activity of lung .alpha.1PI in smokers. Oxidative inactivation of .alpha.1PI in the lungs of cigarette smokers may play a role in the development of pulmonary epmphysema in this group.