Extracellular elastolytic activity in human lung lavage: a comparative study between smokers and non-smokers.
Unrestrained proteolysis in the lung is believed to initiate emphysema, a disease common among tobacco smokers. However, few studies have found extracellular protease activity in human lung lavage. In this investigation, elastase and serine protease activities were measured in bronchoalveolar lavage supernatants (BAL) from patients undergoing routine investigations. Significantly more elastolytic activity (against insoluble [3H]-elastin) was recovered in the lavage of smokers than that of non-smokers. However, no significant difference was found when the levels of serine proteolytic activity (against N-succinyl-L-trialanyl-p-nitroanilide) were compared. The elastolytic component of the protease activity rose from 5% in non-smokers' BAL to over 30% in that of smokers, suggesting that elastase activity is selectively enhanced by smoking. In lavages from most smokers, 80% or more of the elastase activity was serine-dependent, whereas lavages from non-smokers contained variable proportions of serine elastase. Both alpha 1-proteinase inhibitor (alpha 1-PI) and a low molecular weight antiprotease, bronchial mucus proteinase inhibitor (BMPI) were detectable in the lavage samples, the latter contributing up to 76% of the total antiprotease quantified in the lavage. Functional antiprotease was detected in 85% of the lavages. Since there were no differences in either antiprotease levels or functional inhibitory capacities between lavages from smokers and controls, it is concluded that the imbalance in the protease/antiprotease profile of the smokers' lung results from an enhancement of proteases, specifically of elastolytic activity, rather than a reduction in inhibitory capacity.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism; D001999:Bronchoscopy; D004549:Elastin / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009093:Mucus / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism; D012697:Serine Endopeptidases; D012907:Smoking; D007507:Therapeutic Irrigation; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D011480:Protease Inhibitors; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D000515:alpha 1-Antitrypsin; D004549:Elastin; D010450:Endopeptidases; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase