An in vitro model for the induction of angiotensin-converting enzyme in sarcoidosis. Evidence for a soluble ACE-inducing factor.

Normal peripheral blood T-lymphocytes (T) enhance monocyte (Mo) angiotensin converting enzyme (ACE) production in vitro. To evaluate the possible role of a soluble mediator in enzyme induction, the ability of conditioned medium (CM) from Mo-T cocultures to stimulate ACE in fresh Mo was examined. These studies demonstrated that CM promoted a dose-dependent increase in ACE. Generation of the active factor required both Mo and T during culture since neither cell alone yielded active CM. Time course studies revealed that the ACE-inducing activity appeared in CM after 3 to 4 days of culture and increased steadily thereafter. The CM effectively induced ACE in Mo from several donors in contrast to T-dependent induction, which required autologous conditions. The time courses for T-dependent and CM-dependent ACE induction were similar, and the results suggested that the Mo must go through some period of maturation before they respond to CM. We conclude that a soluble mediator derived from Mo-T cocultures enhances Mo ACE production. This in vitro system may be a useful experimental model of the in vivo induction of ACE in the Mo-derived sarcoid epithelioid cell.