Monocytosis associated with the growth of transplanted syngeneic rat sarcomata differing in immunogenicity

Abstract

Summary.-The effect of the growth of two syngeneic transplanted sarcomata of widely differing biological properties on the number of monocytes in the blood of rats was measured (1) by binding of a specific antimacrophage serum to leucocytes, and (2) by sedimenting in a density gradient rosettes between mononuclear cells and antibody-coated sheep red cells under conditions in which B-cells are not brought down. For the 4 syngeneic sarcomata studied there was a progressive increase in the number of monocytes with tumour growth and the values returned to normal a few days after their surgical removal. The extent of monocytosis was related to the immunogenicity of the tumour and was most pronounced for the HSBPA sarcoma, which is highly immunogenic, has a low rate of spontaneous metastasis and contains many macrophages, and least for the MC-3 sarcoma which is essentially non-immunogenic, invariably gives rise to distant metastases and contains only about 8% macrophages. The growth of sarcomata had previously been found to reduce the number of monocytes which enter inflammatory lesions, both non-specific and due to a delayed hypersensitivity reaction. This " antiinflammatory" action of sarcomata which is related to their immunogenicity cannot be ascribed to the preferential uptake of monocytes by the tumours and it is concluded that the monocytes in the blood of tumour-bearers, though increased in number, are modified so that they do not enter sites of inflammation.

Inhibition of Phagocytosis and Glucose Metabolism of Alveolar Macrophages during Pulmonary Tumour Growth

“…Optimal bacterial phagocytosis by AM appears dependent upon humoral opsonic factors (Reynolds, Kazmierowski and Newball, 1975) and the maintenance of glucose metabolism for the provision of metabolic energy (Ouchi, Selvaraj and Sbarra, 1965 (Gee et al, 1974) and increased transport of glucose to provide an energy substrate (Bonventre and Mukkada, 1974;Gudewicz et al, 1976b Pike and Snyderman (1976) of depressed macrophage chemotactic behaviour under the influence of a lowmol.-wt heat-stable inhibitory factor isolated from growing tumours in mice, lend credence to this concept. The present findings of increased macrophage content of the alveolar space and altered macrophage physiological behaviour with tumour growth, must be considered with respect to the data of Eccles, Bandlow and Alexander (1976) and Eccles and Alexanider (1974). They observed increased macrophage content of growing tumours, which was related to the degree of immunogenicity of the tumour, and a parallel impairment of monocyte ability to enter a site of inflammation.…”

“…They observed increased macrophage content of growing tumours, which was related to the degree of immunogenicity of the tumour, and a parallel impairment of monocyte ability to enter a site of inflammation. Tumour growth following transplantation, as investigated in rats with 2 svugenieic transplanted sarcomas, elicited a distinct monocytosis which declined after surgical removal of the tumour (Eccles et al, 1976). They proposed that states of "immunological anergy" with tumour growth may be related to the lack of availability and participation of macrophages in the inflammatory response, although the mechanism remains to be defined.…”

Monocytes and macrophages in malignant melanoma. I. Peripheral blood macrophage precursors

“…The nature of this defect, qualitative or quantitative, was unclear. However, Eccles, Bandlow and Alexander (1976) argue that the defect is qualitative, since they have subsequently shown that such apparently anergic rats show a significant monocytosis rather than a monocytopenia. Furthermore, Normann and Sorkin (1976) have confirmed this observation in rats bearing DMBA-induced tumours.…”

Effect of X-irradiation on host-cell infiltration and growth of a murine fibrosarcoma

“…However, while the irradiated mice were obviously unable to respond immunologically to either FS6 fibrosarcoma cells or SRBC until 2-3 weeks after irradiation, the changes in the macrophage content paralleled the expected rate of recovery of bone marrow and other haemopoietic tissues (Volkman and Collins, 1968). However, as recently demonstrated (Eccles, Bandlow and Alexander, 1976) there is an interrelationship between blood monocyte and tumour macrophage levels and the immunogenicity of the tumour, implying that the level of blood monocytes and tumour macrophages is under immunological control. The presence of T cells, albeit in low numbers, within the FS6 tumour mass, may be relevant to the mechanism determining the level of macrophages found associated with tumours, especially if it can be demonstrated that they show an affinity for the FS6 neo-39 plastic cells.…”