Monocyte heterogeneity in angiotensin-converting enzyme induction mediated by autologous T lymphocytes

Abstract

The ability of monocyte subpopulations to be induced selectively by T lymphocytes to synthesize enhanced levels of angiotensin‐converting enzyme (ACE) was examined using an in vitro model employing normal peripheral blood monocytes and T lymphocytes. Separation of monocytes into subpopulations on the basis of buoyant density indicated no difference in the ability of the resulting monocyte subpopulations to produce basal levels of ACE when cultured in the absence of T lymphocytes. However, the subpopulations differed significantly in their ability to synthesize enhanced levels of ACE in response to the presence of autologous T lymphocytes; low‐density monocytes were induced by T lymphocytes to synthesize three‐fold more ACE than were highdensity monocytes. Surface antigen labelling using MoAbs demonstrated that the low‐density monocyte subpopulations also had a significantly higher percentage of Leu‐M2⁺ monocytes compared with the high‐density monocyte subpopulations. When monocytes were separated on the basis of the presence of the Leu‐M2 antigen using an immune rosetting technique, T lymphocytes were able to induce significantly elevated levels of ACE in the Leu‐M2⁺ enriched monocyte subpopulation but were unable to induce ACE beyond basal levels in the Leu‐M2⁺‐depleted monocyte subpopulation. These results demonstrate that monocytes are heterogeneous with respect to their ability to be induced by T lymphocytes to synthesize ACE. This raises the possibility that selective accumulation of a monocyte subpopulation in the granulomatous inflammation of sarcoidosis may be one of the factors required for elevated ACE synthesis in the resulting granuloma epithelioid cells.