EFFECTS OF SULFHYDRYL AND NON-SULFHYDRYL ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS ON MITOGEN-INDUCED PROLIFERATION OF MOUSE SPLENOCYTES

The effects of some angiotensin converting enzyme (ACE) inhibitors (al acepril, captopril, enalaprilat, enalapril maleate and lisinopril) on mitogen-induced proliferation of B- and T-lymphocytes were evaluated i n C57 mouse spleen cells. Concanavalin A (Con A), a specific T-lymphoc yte mitogen, and lipopolysaccharide (LPS), a specific B-lymphocyte mit ogen, were used in these studies. Optimum doses of the mitogens were d etermined (Con A, 2 mcg/ml; LPS, 50 mcg/ml) since the concentration of mitogen used may itself affect the proliferative response. Both capto pril and alacepril dose-dependently enhanced mitogen-induced prolifera tion of B- and T-lymphocytes. In LPS-stimulated B-lymphocytes, the eff ective stimulatory concentration range was 0.1-20 mM for captopril and 0.05-10 mM for alacepril. In Con A-induced T-lymphocytes, the effecti ve stimulatory concentration range was 0.02-20 mM for captopril and 0. 05-10 mM for alacepril. Mitogen-induced proliferative responses were i nhibited when concentrations of captopril and alacepril exceeded 20 mM and 10 mM, respectively, which affected the number of viable cells. E nalapril dose-dependently inhibited mitogen-induced proliferation of B -lymphocytes (0.2-10 mM) and T-lymphocytes (0.15-10 mM). Enalaprilat, the active parent diacid of enalapril, had a weaker inhibitory effect on mitogen-induced proliferative responses of both B- (2-20 mM) and T- lymphocytes (0.4-20 mM). Lisinopril, a lysine derivative of enalaprila t, also inhibited mitogen-induced proliferation of B- (4-36 mM) and T- lymphocytes (4-36 mM). The ACE inhibitors had different effects (enhan cement or inhibitory) on mitogen-induced lymphocyte proliferation. The immunomodulatory effect of captopril may be associated with its free sulphydryl group, while the mechanisms of the non-sulphydryl (enalapri l and enalaprilat) and sulphur-containing (alacepril) inhibitors remai n uncertain.