Pathways of tumour cell killing by activated macrophages: Both tumour cell membrane and nucleus can be the primary target

: Plasma membrane and nucleus can be primary targets of tumour cell killing by activated macrophages (AMo). Necrotic-type cytotoxicity with loss of membrane integrity and cytoplasmic swelling was expressed by AMo from normal and from perforin-deficient mice, indicating that perforin was not involved. Incubation with AMo consistently triggered the release of thymidine from prelabelled targets, whereas chromatin condensation and small DNA fragments were only occasionally detected. It is shown by means of Pulsed-Field Gel Electrophoresis that DNA degradation in target cells is a slowly progressing process that may stop at any time, indicating that nuclear-type killing doesnot necessarily lead to the formation of low molecular weight fragments. Neither Fas nor the p55 tumour necrosis factor receptor appear to be involved in signalling nuclear-type killing. Accordingly, AMo do mediate membrane- and nuclear-type killing but the mechanisms differ from those identified in T cell cytotoxicity.