CYTOTOXIC EFFECTS OF ALKYLPHOSPHOCHOLINES OR ALKYLPHOSPHOCHOLINE-LIPOSOMES AND MACROPHAGES ON TUMOR-CELLS

The influence of the alkylphosphocholines (APC) on macrophage activati on to tumor cytotoxicity was investigated in vitro with both mouse per itoneal and rat liver macrophages. For this purpose the compouds were used either in micellar or in liposomal form. The cytotoxic effect of micellar or liposomal APC was increased with prolongation of the aliph atic chain and was reduced for the liposomal form. Peritoneal macropha ges incubated with APC-liposomes gave a comparable cytotoxic effect on MethA cells to that of the free, highly toxic APC alone, These liposo mes can activate rat liver macrophages (Kupffer cells) in vitro to a m oderate tumor cytotoxicity on C26 colon carcinoma cells, while the mic ellar APC were toxic to macrophages. A significant release of NO-radic als from peritoneal macrophages was obtained with Liposomes but not wi th micellar lipid. The release of tumor necrosis factor (TNF) was stim ulated by incubation with micellar or liposomal HPC. Whereas the micel lar HPC was comparable to lipolysaccharide (LPS) in TNF release stimul ation, the HPC-liposomes caused a much higher release.