Possible mechanisms of emphysema in smokers: cigarette smoke condensate suppresses protease inhibition in vitro.

To study the possible role of suppression of antiproteases by cigarette smoke in the pathogenesis of pulmonary emphysema in smokers, the following experiments were carried out. 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 were then allowed to diffuse through the impregnated gels toward a counter-diffusing sample of antiprotease. The effectiveness of the antiprotease in blocking the enzyme was determined from the extent of elastolysis. The elastin substrates used included beef ligament elastin and dog lung elastin. The enzymes used were porcine pancreatic elastase and pure human leukocyte elastase. The antiproteases tested included human serum, pure human a1-antitrypsin, human bronchopulmonary lavage fluid, and a synthetic chloromethyl ketone inactivator of elastase. The results showed that whole, unfractionated cigarette smoke condensate suppressed all of the antiproteases tested, except for the chloromethyl ketone. These observations are discussed in terms of the protease-pathogenesis model of pulmonary emphysema.