Quantitative stereological studies on the mechanism of immunosuppressive effect of nitrogen mustards of benzimidazole derivatives: the role of polymorphonuclear leukocytes and mononuclear phagocytes

The effect on antigen uptake and digestion in macrophages and polymorphonuclear leukocytes (PMNL) of 2 compounds of a series of benzimidazole nitrogen mustard derivatives has been investigated by ultrastructural quantitative stereological techniques in order to enlighten some mechanisms of the immunosuppressive effect of especially one of the chemicals. One compound, ZIMET 3393 (Cytostasan), is a powerful cancerostatic with only moderate immunosuppressive side effects while ZIMET 3164 proved an effective immunosuppressant with low cytostatic action. Results of a recent study (FRITSCH and GOTHE 1979) have lent support to the hypothesis that immunosuppression can be induced by an inhibition of antigen processing by macrophages through a membrane-stabilizing effect of the chemicals under investigation. It can be shown in the present study that in the case of ZIMET 3164 an increased competitive antigen phagocytosis and digestion takes place in PMNL. This alternative pathway of antigen processing is suggested to be ineffective with respect to enhancement of immune responses compared with that through macrophages, thus providing an additional possible mechanism of chemical immunosuppression.