Lavage angiotensin-converting enzyme as a marker of lung injury.
The source of angiotensin-converting enzyme (ACE) in lavage fluid remains controversial. I reassessed the levels of ACE in lavage fluid in contrasting models of lung injury in rats. In all 3 models examined, there was at least a 3-fold elevation in both ACE activity and total protein levels. However, determination of enzyme activity relative to total protein content (enzyme specific activity) revealed contrasting patterns. High dose intratracheal bleomycin instillation (500 micrograms) induced an increase in ACE activity relative to total protein. When a lower dose of bleomycin (50 micrograms) or when a 30-h exposure to 100% oxygen were used, both ACE and protein increased but enzyme specific activity did not change. In contrast, exposure to 100% oxygen for 48 h or to alpha-naphthylthiourea, an agent that rapidly induces protein edema without cell injury, caused a decrease in enzyme specific activity. The enzyme found in lavage fluid in these models is identical to the lung tissue enzyme with respect to cofactor requirements, inhibition by captopril, and has an apparent molecular weight of 175 kDa by SDS-polyacrylamide gel electrophoresis. These studies clearly refute the null hypothesis that lavage ACE levels in the injured lung merely reflect altered bulk protein transmigration.
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis*; D008171:Lung Diseases / Q000201:enzymology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D011506:Proteins / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
D011506:Proteins; D001761:Bleomycin; D007703:Peptidyl-Dipeptidase A