Demonstration of a free elastolytic metalloenzyme in human lung lavage fluid and its relationship to alpha 1-antiprotease.
Although the human alveolar macrophage in tissue culture can secrete an elastolytic metalloenzyme that is not inactivated by alpha 1-antiprotease (AAP), levels of this proteolytic activity and its relationship to AAP in human lung lavage fluid ( HLF ) are unknown from previous studies. Therefore, we measured elastolytic activity in concentrated (20- to 30-fold) HLF from 15 smokers and 10 nonsmokers and related results to measurements of AAP in these fluids. Activity (mean +/- SEM) against a C elastin substrate (expressed as nanograms of porcine pancreatic elastase equivalents per milligram of lavage fluid protein) in smokers, 18.9 +/- 6.7, significantly exceeded (p = 0.05) levels present in nonsmokers, 4.4 +/- 1.8. With the synthetic elastin-like chromophore substrate succinyl-trialanine-nitroanilide ( SLAPN ), activity in individual samples was reduced 79% by EDTA, a metalloproteinase inhibitor, whereas activity was reduced by only 29% in the presence of PMSF, a serine proteinase inhibitor. In addition, using a pooled sample of HLF and C elastin substrate, 80% of activity against the elastin substrate was eliminated by EDTA, whereas 51% was eliminated by PMSF. The activity measured with C elastin substrate correlated inversely with antigenic AAP (r = -0.05, p = 0.01), but no correlations were found between this activity and HLF cell number, cell viability, differential count, or subject smoking history. The detection of activity with C elastin in HLF , with primarily a metalloenzyme inhibitor profile, in the presence of antigenically detectable AAP, may have pathogenetic relevance for emphysema in humans.
D000328:Adult; D004492:Edetic Acid / Q000494:pharmacology; D004549:Elastin / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008297:Male; D009842:Oligopeptides; D010196:Pancreatic Elastase; D011480:Protease Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000201:enzymology; D012907:Smoking; D007507:Therapeutic Irrigation; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D009842:Oligopeptides; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; C015516:succinyl-trialanine-4-nitroanilide; D004549:Elastin; D004492:Edetic Acid; D010196:Pancreatic Elastase