[Stereologic studies on the mechanism of action of two 1,2-substituted 5-bis-(beta-chlorethyl)aminobenzimidazole derivatives].

The effects of two 1,2-substituted 5-bis-(beta-chloroethyl)-amino-benzimidazole derivatives on the course of phagocytosis in murine peritoneal macrophages after intraperitoneal injection of bovine fibrin has been investigated by means of quantitative ultrastructural stereologic methods. One of the compounds, IMET 3164, is a strong immunosuppressive agent with membrane-stabilizing effects while the other one, IMET 3393 (Cytostasan) is an effective cytostatic drug with weak immunological effects. From the results the following conclusions can be drawn. After stimulation by intraperitoneal injection of fibrin, macrophages of untreated animals show a rapid antigen uptake and digestion as well as a formation of new lysosomes. Simultaneously, an immigration into the peritoneal cavity of monocytes and an emigration of strongly storing macrophages takes place. After treatment with either benzimidazole-N-mustard derivative, most pronounced after IMET 3164, a delayed antigen phagocytosis and digestion and an inhibition of formation of new lysosomes can be observed. Likewise, the intraperitoneal cell fluctuation is strongly reduced after IMET 3164. The findings lend support to the hypothesis that immunosuppression may be induced, among other mechanisms, by an inhibition of phagocytosis and antigen processing by means of membrane-stabilizing compounds.