Role of Angiotensin-converting Enzyme in Bacille Calmette-Guérin-induced Granulomatous Inflammation. Increased Angiotensin-converting Enzyme Levels in Lung Lavage and Suppression of Inflammation with Captopril

Lung lavage levels of angiotensin-converting enzyme (ACE)-like activity were increased in C57BL/6 mice with Bacille Calmette-Guérin (BCG)-induced chronic granulomatous pulmonary inflammation and splenomegaly. Contrariwise, ACE activity was not increased in lung lavage fluids of CBA mice that developed only minimal pulmonary inflammation in response to BCG. ACE-like activity correlated with the intensity of inflammation and Captopril, a specific competitive inhibitor of ACE activity, markedly suppressed the induction and maintenance of the BCG-induced inflammatory response in both lungs and spleen. It was necessary, however, to provide sustained treatment with large doses of Captopril in order to reduce the inflammatory response. After a single intraperitoneal injection of Captopril, ACE levels in lung lavage of BCG-injected mice were reduced but returned to preinjection levels or greater within 24 h. The highest dose of Captopril was more effective in reducing the lung fluid level of ACE in BCG-inflamed lungs. This suggests that sustained daily injections of Captopril were necessary to maintain reduced ACE levels. In vitro studies indicated that high concentrations of Captopril did not affect macrophage mobility or chemotactic activity for macrophages. Thus, ACE may act as a molecular mediator of BCG-induced granulomatous inflammation in the lung.