the role of overproduction of nitric oxide in apoptosis of balb/c mice macrophages infected with leishmaniamajor in vitro

nitric oxide (no) derived from activated macrophages has been shown to be crucial for the host's leishmanicidal activities. excess no, however, can in¬duce apoptosis in some cell types, including macrophages. in the present inves¬tigation, we studied the role of no in inducing apoptosis of balb/c mice mac¬rophages infected with leishmania major in vitro. the peritoneal macrophages were harvested and cultured with or without l.major in the presence of a donat¬ing reagent (s-nitroso-n-acetylpenicillamine (snap)) or an inhibitor of no synthase (ng -methyl-l-arginine (nmma)). the concentration of no in cul¬ture supernatants was measured after 18 hours incubation. simultaneously, mac¬rophages undergoing apoptosis were identified by fluorescence and electron mi¬croscopy. the results showed an increase in apoptosis rate in parallel to nitrite production in macrophages cultured in the presence of snap. although mac¬rophages infected with l.major had no significant increase in no production, they showed a significant increase in apoptosis rate. besides, macrophages cul¬tured with nmma, had a decreased no production but the apoptosis rate in¬creased. therefore, mechanisms involved in apoptosis induction in the last two groups may be different from no overproduction.