APOPTOSIS AS A MECHANISM OF LECTIN-DEPENDENT MONOCYTE-MEDIATED CYTOTOXICITY

In this study we investigated the mechanisms of cytotoxicity mediated by pokeweed mitogen (PWM)-activated human peripheral blood monocytes. By using DNA electrophoresis and propidium iodide (PI)-DNA staining fl ow cytometry, we demonstrated that apoptotic cell death of target U937 cells and Raji cells was induced in lectin (PWM)-dependent monocyte-m ediated cytotoxicity (LDMC). The LDMC-mediated DNA fragmentation in U9 37 cells and Raji cells was induced in lectin (PWM)-dependent monocyte mediated cytotoxicity(LDMC). The LDMC-mediated DNA fragmentation in U 937 cells was completely inhibited by anti-TNF alpha monoclonal antibo dy (mAb), but not by the addition of monosaccharide (N-acetylglucosami ne, GlcNac, a sugar specifically recognized by PWM and a lectin-like r eceptor on monocytes). In contrast, GlcNAc inhibited the DNA fragmenta tion in Raji cells induced by LDMC which the anti-TNF alpha mAb had no effect. PWM was found to stimulate the production of nitric oxide (NO ) from monocytes. Tho NO-production was enhanced in the presence of ta rget Raji cells, while the enhanceme nt LL as abolished by the treatme nt with GlcNAc. By flow cytometry, we found that PWM bound to tumour. cells as well as monocytes, and inhibited the expression of HLA-DR ant igen on tumour cells. These results suggest that the presence of lecti n molecules on the surface of monocytes and tumour cells may bring the two cells together, thus facilitating the induction of apoptosis in t arget cells by triggering the production of cytolytic factors (TNF and NO) and the modification of target cell surface antigen (HLA-DR).