An in vitro model for the induction of angiotensin-converting enzyme in sarcoidosis: possible parallels to the immune response.
The T lymphocyte-dependent induction of angiotensin-converting enzyme (ACE) in cultured normal peripheral blood monocytes is a useful experimental model of the in vivo induction of ACE in monocyte-derived sarcoid granuloma epithelioid cells. Because of the possible parallels between ACE induction and immune activation in this model system, the ability of T lymphocytes to induce ACE was compared under a variety of conditions to their immune activation, as measured by 3H-thymidine incorporation. The ability of T cells to induce monocyte ACE was compared in the presence or absence of proliferation. The on-going autologous mixed lymphocyte reaction did not stimulate a further increase in ACE activity compared to the cultures where no proliferation occurred, showing that ACE induction does not depend on full immune T cell activation. Recognition of self though is crucial since in allogeneic monocyte/T lymphocyte co-cultures ACE was not induced above the levels found in monocytes alone. It was also shown that the immune cooperation between monocytes and T cells in reaction against monocyte-presented soluble antigen prevented T lymphocyte stimulated monocyte ACE induction, suggesting the possibility that self class II antigen recognition rather than foreign antigen recognition may be involved in the pathogenesis of sarcoidosis. Reaction to T mitogens (PHA, ConA), known to stimulate the production of interleukins, decreased monocyte ACE synthesis, indicating that soluble ACE-inducing factor probably does not belong to the group of immune interleukins.
Vuk-Pavlović
Z
Z
Thoracic Diseases Research Unit, Mayo Clinic/Foundation, Rochester, MN 55905.
Rohrbach
M S
MS
D000328:Adult; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D012507:Sarcoidosis / Q000201:enzymology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D008934:Mitogens; D007703:Peptidyl-Dipeptidase A