Demonstration of a free elastolytic metalloenzyme in human lung lavage fluid and its relationship to alpha1-antiprotease

M. S. Niederman, L. L. Fritts, W. W. Merrill, R. B. Fick, R. A. Matthay, H. Y. Reynolds, J. B. Gee

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24 Scopus citations

Abstract

Although the human alveolar macrophage in tissue culture can secrete an elastolytic metalloenzyme that is not inactivated by alpha1-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 14C 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 14C elastin substrate, 80% of activity against the elastin substrate as eliminated by EDTA, whereas 51% was eliminated by PMSF. The activity measured with 14C elastin substrate correlated inversely with antigenic AAP (r = -0.5, 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 14C elastin in HLF, with primarily a metalloenzyme inhibitor profile, in the presence of antigenically detectable AAP, may have pathogenetic relevance for emphysema in humans.

Original languageEnglish (US)
Pages (from-to)943-947
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume129
Issue number6
StatePublished - 1984

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

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