The subversion of normal and Corynebacterium parvum-stimulated macrophage responses by the Landschutz ascites carcinoma
The objective of this study was to investigate the influence of the Landschutz ascites carcinoma (LAC) on macrophage activity in normal mice and those given the experimental immunotherapeutic agent Corynebacterium parvum (C.parvum). Tumour cell injection caused transient inhibition of the activity of the mononuclear phagocyte system (MPS) in both normal and C.parvum - treated hosts, as evidenced by impaired clearance of intravenous colloidal carbon and a shift in the distribution of antigen (sheep red blood cells) from the liver to the spleen. Similar depressions in the phagocytic index were observed in tumour-bearing mice receiving other MPS stimulating agents : endotoxin, zymosan and stilboestrol. Granuloma production in the liver in response to C.parvum was inhibited in tumour-bearing mice and macrophage proliferation within the spleen was also substantially reduced. Maturation of macrophages into epithelioid cells, characteristically formed in response to C.parvum, was not observed within granulomas of tumour-bearing mice. This inhibitory effect could not be ascribed to sequestration of microorganism within the growing tumour, or to diversion and sequestration of mononuclear phagocytes in the tumour, or to the presence of the lactate dehydrogenase-elevating virus in either host or tumour cells, or to decreased numbers of circulating monocytes in the bloodstream; ascites fluid was, itself, a source of colony- stimulating factor for monocytopoiesis and granulopoiesis in vitro. Ascites fluid and tumour-bearer serum (TBS) were chemotactic for neutrophils but inhibited the migration of macrophages, obtained from resident or stimulated peritoneal cell populations. This provides a mechanism whereby inflammatory responses of macrophages, but not neutrophils, could have been reduced systemically in tumour-bearers. The depression of macrophage activity by the LAC was attributed to heat-stable tumour-associated factor(s) present in ascites fluid and TBS, which were equally effective on resident and stimulated macrophage populations.