Amounts of angiotensin-converting enzyme mRNA reflect the burden of granulomas in granulomatous lung disease.

A number of granulomatous lung diseases, including sarcoidosis, are associated with an increase in angiotensin-converting enzyme (ACE) activity. To evaluate whether the amount of ACE activity reflects the burden of granulomas, we used an animal model of granulomatous lung disease caused by injecting killed Mycobacterium butyricum intravenously into mice after a primary intracutaneous injection with Freund's complete adjuvant. In this model, essentially all of the granulomas are present in the lung. RNA was isolated from one lung and assayed for ACE mRNA. The other lung was evaluated histologically; the area of lung occupied by granulomas was determined by morphometry. We found that total lung RNA and RNA specific for ACE increased in close correlation with the area of granulomas. These findings provide direct evidence that the amount of ACE activity in granulomatous disease reflects the total burden of granulomas. This may be a useful model to further evaluate ACE regulation in granulomatous lung disease.