Induction of macrophage antitumor activity by gamma radiation

The authors have developed a model system for examination of macrophage-mediated tumor cells lysis, using the murine macrophage tumor cell line RAW 264.7. These cells, like normal macrophages, exhibit a strict requirement for interaction with both interferon-γ (IFN-γ, the priming signal) and bacterial lipopolysaccharide (LPS, the triggering signal) in the development of tumor cytolytic activity. In this system, the priming effects of IFN-γ decay rapidly following withdrawal of this mediator and the cells become unresponsive to LPS. They have recently observed that gamma radiation of the RAW 264.7 cells results in development of a primed state which is stable and responsive to LPS triggering for a least 48 hours. Irradiation-induced development of the primed phenotype is not solely the result of cytostatic effects as LPS treatment alone results in marked decreases in 3H-TdR incorporation in the absence of cytolytic potential. In addition to delivering the priming signal for tumor cytotoxicity, irradiation of this cell line results in changes in cell morphology that are typical of activation. Finally, treatment with irradiation results in increased cell surface expression of MHC-encoded Class I antigens; however, Class II antigen expression is not induced. Thus, the effects of gamma radiation on this cell line are strikingly similar to those resulting from incubation with IFN-γ