Suppression of macrophage oxidative metabolism by products of malignant and nonmalignant cells.

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Abstract
Each of 11 [mouse] tumors [P815 mastocytoma cells, PU5-1 lymphoma cells, L1210 lymphoma cells, EL-4 lymphoma cells, TLX9 lymphoma cells, YAC lymphoma cells, MC-6 mammary carcinoma cells, GIF sarcoma cells, adenocarcinoma 755 cells, RC-2 renal adenocarcinoma cells and J774 histiocytoma cells] tested produced a factor that markedly suppressed the ability of macrophages to release H2O2 or .**GRAPHIC**. in response to phorbol myristate acetate or zymosan. Of 7 normal cell types, 4 produced a similar activity, which was 3.5-7 times lower in titer than that in tumors cell-conditioned medium (TCM), and which was much more rapidly reversible in its effects. TCM caused 50% inhibition of H2O2 release when it was present in the medium for 48 h at a concentration of 13%, or when 100% TCM was present in the medium for 18 h. The H2O2-releasing capacity of macrophages incubated in TCM only returned to control levels by 6 d [days] after its removal. TCM prevented augumentation of H2O2-releasing capacity by lymphokines. The titer of suppressive activity in TCM depended on both the concentration of tumor cells and the duration of their incubation. TCM did not augment the activity of catalase, myeloperoxidase, glutathione peroxidase or glutathione reductase or the content of glutathione within macrophages, suggesting that decreased synthesis rather than increased catabolism was responsible for reduced secretion of H2O2. Suppression of the release of H2O2 or .**GRAPHIC**. by TCM was a relatively specific effect, in that TCM increased macrophage spreading and adherence to glass while exerting little influence on rates of phagocytosis, synthesis of protein, or secretion of lysozyme, plasminogen activator, or arachidonic acid and its metabolites. Tumor cells and some normal cells can secrete a factor that selectively deactivates macrophage oxidative metabolism.