Studies on the mechanism of macrophage cytotoxicity.
The interactions with tumor target cells of resident and BCG-activated murine peritoneal macrophages (M phi) as well as of BCG-activated M phi additionally stimulated by a lymphokine-like factor were investigated in order to get some insight into the cytolytic process mediated by activated M phi. The lymphokine-like factor enhancing the cytotoxicity of BCG-activated M phi (MCF) was isolated and partially purified from cell-free fluid of rat Zajdela ascites hepatoma. M phi cytotoxicity was determined by a modified 51Cr release assay. Scanning and transmission electron microscopic findings suggested a two-step mechanism of target cell lysis: a first step of specific attachment of processes of M phi on the target cell surface and a second step with transport of lysosome-like vesicles to the target cells obviously with liberation of these vesicles in the immediate vicinity of target cells resulting in a local accumulation of cytolytic substances. This interpretation was supported by findings after treatment of interacting effector and target cells with amphotericin B and bestatin which substances were modifying M phi cytotoxicity. MCF caused only an augmentation of M phi cytotoxicity without qualitative differences to the cytolytic action of merely BCG-activated M phi.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009368:Neoplasm Transplantation; D011554:Pseudopodia / Q000648:ultrastructure; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000648:ultrastructure
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D000666:Amphotericin B; D007930:Leucine; C012211:ubenimex