Comparison of the T lymphocyte-dependent induction of angiotensin-converting enzyme and leucine aminopeptidase in cultured human monocytes

Abstract

The T lymphocyte-mediated induction of angiotensin-converting enzyme (ACE) in cultured autologous peripheral blood monocytes has been proposed as a model system for the investigation of the in vivo induction of ACE in the monocyte-derived granuloma epithelioid cells of some granulomatous diseases such as sarcoidosis. The studies described here were designed to evaluate the specificity of the model system by comparing the parameters for induction of ACE with those for the induction of another monocyte metallo-ecto-peptidase, leucine aminopeptidase (LAP). The concentration of LAP in freshly isolated monocytes was 0.09 mU/10(6) monocytes (s.e.m. 0.04) and increased to a maximal value of 0.19 mU/10(6) monocytes (s.e.m. 0.32) after 3 days when monocytes were cultured alone. ACE was not detectable in freshly isolated monocytes. However, after 6 days of culture, monocytes contained 0.22 mU ACE/10(6) monocytes (s.e.m. 0.04). Comparison of the levels of ACE and LAP induced during culture of monocytes alone indicated that the induction of these two enzymes were correlated. The induction of both enzymes was further enhanced by the presence of T lymphocytes in a dose-dependent manner. At 4 x 10(6) T lymphocytes per culture, ACE levels increased to 1.81 mU/10(6) monocytes (s.e.m. 0.24) and LAP levels to 1.03 mU/10(6) monocytes (s.e.m. 0.35). The enhancement of ACE activity required autologous lymphocytes, while heterologous T lymphocytes were equally effective in inducing LAP. Comparison of the levels of ACE and LAP induced during coculture of autologous T lymphocytes and monocytes from 21 independent donors, demonstrated no correlation between the induction of ACE and LAP. These data indicate that, although T lymphocytes also enhance the induction of LAP, the underlying mechanism must differ from that of ACE induction.