Interaction between cisplatin treated murine peritoneal macrophages and L929 cells: involvement of adhesion molecules, cytoskeletons, upregulation of Ca2+ and nitric oxide dependent cytotoxicity

Murine peritoneal macrophages on treatment with cisplatin (10 microg/ml) showed increased binding to L929 cells. Cisplatin treated macrophage on co-incubation with L929 cells form a distinct cytoplasmic contact between the two cells. The plasmalemmae of the two cells fuse over a large surface area. The formation of contact between the cisplatin treated macrophage and L929 cell results in the induction of apoptosis in L929 cell. Untreated macrophages did not form a contact with L929 cells and no apoptosis is observed in L929 cells. Immunofluorescence microscopical studies clearly show the participation of cytoskeleton and the adhesion molecules in the formation of contact between the two cells. Further, a significant enhancement of the expression of iNOS and cytosolic Ca2+ was observed in cisplatin treated macrophages co-incubated with L929 cells. Cisplatin treated macrophages produced significant amount of NO when co-incubated with L929 cells, while there was minimal production of NO by untreated macrophages co-incubated with L929 cells. Cisplatin treated macrophage-induced L929 cell death was NO dependent, since L-NMMA (500 microM) significantly inhibited the cytotoxicity of L929 cells. The addition of excess L-arginine (2mM) reversed the L-NMMA induced inhibition of NO production and L929 cell cytotoxicity.