POSSIBLE MECHANISMS OF EMPHYSEMA IN SMOKERS - CIGARETTE-SMOKE CONDENSATE SUPPRESSES PROTEASE INHIBITION INVITRO

Abstract

Elastin-agarose gels were impregnated with cigarette smoke condensate dissolved in dimethyl sulfoxide or with the solvent alone. This procedure affected neither local pH of the gel nor subsequent physical behavior (diffusion) of antiprotease. Elastases from various sources then diffused through impregnated gels toward a counter-diffusing sample of antiprotease. Effectiveness of the antiprotease in blocking the enzyme was determined from extent of elastolysis. Elastin substrates used included beef ligament elastin and dog lung elastin. Enzymes used were porcine pancreatic elastase and pure human leukocyte elastase. Antiproteases tested included human serum, pure human .alpha.1-antitrypsin, human bronchopulmonary lavage fluid and a synthetic chloromethyl ketone inactivator of elastase. Whole, unfractionated cigarette smoke condensate apparently suppressed all antiproteases tested, except for the chloromethyl ketone. Observations are discussed in terms of the protease-pathogenesis model of pulmonary emphysema.