Macrophage Activation for Tumor Cytotoxicity: Reactivity of Peritoneal and Bone Marrow Macrophages

Abstract

Peritoneal macrophages recovered from mice infected with intracellular parasites such as Mycobacterium bovis, strain BCG,Toxoplasma gondii or Listeria monocitogenes exert non specific cytotoxic activity against tumor cells in vitro (1 ,2).Macrophage cytotoxicity is selectively expressed against neoplastic cells.Tumor cells,derived from viral or chemical carcinogen-induced or spontaneous syngeneic and non syngeneic tumors,were found to be quantitatively more susceptible to macrophage cytophatic effects than were non neoplastic cells.Tumor cell killing requires cell to cell contact;soluble cytotoxic factors released by macrophages or by macrophage-tumor cell interactions have not been described.A cinemicrographic analysis revealed that macrophage-tumor cell interactions are characterized by repeated and relatively short (2 hr.) contacts inducing permanent tumor cytostasis and degenerative morphological changes (3).The development of a cytotoxicity assay based on radioisotope release facilitated quantitative analysis of macrophage tumoricidal activity (4).Tumor cell death was evaluated as release of tritiated thymidine from prelabeled target cells into supernatant culture fluids BCG-activated macrophages induced significant release of ³HTdR from tumor cells by 24 hours;however,optimal measurement of tumor cytotoxicity (50% total counts) was observed after 48–72 hours.Macrophages from uninfected mice or from oil-, starch- or thioglycollate induced peritoneal exudates had little effect on labeled tumor mono-layers.