Inhibition by the Landschütz ascites carcinoma of the granulomatous inflammatory response to C. parvum

Abstract

Summary.-I.p. or i.v. administration of Corynebacterium parvum (CP) to MF1 mice induces a generalized inflammatory response, associated with marked hepatosplenomegaly and accompanied by a pronounced granulomatous response in the liver. Injection of the Landschutz ascites carcinoma (LAC) 24 h after CP substantially reduced the intensity of the inflammatory response, and decreased both the frequency and size of the hepatic granulomas, as revealed by morphometric analysis of histological sections.The difference in cellular composition of the granulomas between the experimental groups, as revealed by light microscopy, was further emphasized and characterized by ultrastructural studies. These revealed the predominance of macrophages within the granulomas in tumour-bearing mice, in contrast to the predominance of epithelioid cells in the lesions which developed in mice given CP alone.Our experimental findings show that the inhibitory effect of the growing LAC on granuloma formation in response to CP cannot be ascribed to (a) sequestration of the microorganism within the growing tumour, (b) a nonspecific inflammatory stimulus, (c) diversion and seqestration of mononuclear phagocytes in the growing tumour or (d) the presence of lactate dehydrogenase-elevating virus in either the host or tumour cells. The inhibition of liver granuloma formation is consistent with an effect mediated by soluble, heat-stable tumour-associated factor(s).

Tumour-Induced Suppression of Delayed-Type Hypersensitivity in the Mouse: Independence of Cyclophosphamide-Sensitive Suppressor Cells

“…We have previously shown that the growing LAC and soluble tumour-associated factors suppress ma crophage activities [19] and monocyte inflammatory responses in vivo [20] and in vitro [18]. There is, how ever, no reduction in the number of circulating mono cytes associated with growth of the tumour.…”

“…Mice received 106 viable LAC cells obtained by washing the cell sus pension twice in saline and adjusting to the appropriate concentra tion; viability always exceeded 95% as estimated by trypan blue dye exclusion. There was no contamination of the tumour-bearing mice with lactate dehydrogenase virus, as assessed by serum lactate de hydrogenase activity and electron microscopic examination of the LAC cells or host lymphoreticular organs [20]. The tumour was also mycoplasma-free as assessed by negative staining using bisbenzimid fluorochrom [4].…”

Investigation of the Procoagulant Activity Present in Ascitic Fluid and Serum of Mice Bearing the Landschütz Ascites Carcinoma

“…The Landschutz ascites carcinoma was passaged in female MF1 mice (8 12 weeks old) by intraperitoneal injection [16]. Washed tumour cells (day 11).…”

Cancer-Induced Alterations in T-Cell Subsets in Normal and Cyclophosphamide-Treated Mice

“…In previous reports, we have shown that growth of the Landschiitz ascites carcinom a (LAC) in mice is as sociated with im pairm ent of cell-mediated immune responses [8], m acrophage activities in vivo and in vitro [6,7] and the production, by splenic T cells, of various lymphokines [5]. The capacity of the tum our to subvert delayed-type hypersensitivity reactions and cytokine production has been observed in both nor mal anim als and in hosts pretreated with high dose cyclophospham ide (Cy) [5], an agent believed to de plete selectively the precursors of T-suppressor (Ts) cells [9,12,13,15], The latter observation suggests that the im m unosuppressive action of the LAC is in dependent o f Ts.…”