Angiotensin-converting enzyme inhibitor captopril prevents activation-induced apoptosis by interfering with T cell activation signals

Captopril is an orally active inhibitor of angiotensin-converting enzyme (A CE) which is widely used as an anti-hypertensive agent. In addition to its ability to reduce blood pressure, captopril has a number of other biologica l activities. Recently the drug was shown to inhibit Fas-induced apoptosis in human activated peripheral T cells and human lung epithelial cells. In t his study, we investigated whether captopril blocks activation-induced apop tosis in murine T cell hybridomas, and found that captopril inhibited IL-2 synthesis and apoptotic cell death upon activation with anti-CD3 antibody. In addition, captopril inhibited an inducible caspase-3-like activity durin g activation-induced apoptosis. On the other hand, captopril did not interf ere with Fas signalling, since anti-Fas antibody-induced apoptosis in Fas() Jurkat cells was unaffected by the drug. Furthermore, we examined whether captopril blocks activation-induced apoptosis by interfering with expressi on of Fas, Fas ligand (FasL), or both on T cell hybridomas. FasL expression on activated T cells was significantly inhibited by captopril, whereas up- expression of Fas was partially inhibited, as assessed by cell surface stai ning. Taking all data together, we conclude that captopril prevents activat ion-induced apoptosis in T cell hybridomas by interfering with T cell activ ation signals. Captopril has been reported to induce systemic lupus erythem atosus syndrome, and our findings may be useful for elucidating the mechani sm of captopril-induced autoimmunity.