Role of Macrophages in the Tumor-Induced Suppression of Mitogen Responses in Rats

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Abstract
Concanavalin A (Con A) responses by spleen cells from tumor-bearing (TB) female (WAG/Rij × BN/Bi)F1 rats were markedly depressed, as determined by incorporation of 14C-Iabeled thymidine ([14C]TdR). This decline in Con A responsiveness was accompanied by a rise (from ±6 to ±14%) in the relative number of phagocytic cells in suspensions of spleen cells from TB animals (TB spleen cells). Treatment of TB spleen cells with carbonyl iron powder or subjecting them to glass adherence led to a complete restoration of the Con A response and a return to normal in the numbers of macrophages. The restorative effect of macrophage depletion was negated by the addition of 10% peritoneal exudate cells from normal animals. The addition of extra numbers of macrophages (5% or more) to normal spleen cell cultures caused the inhibition of [14C]TdR incorporation after Con A stimulation. Thus this study suggests the possibility that the low Con A responsiveness of TB spleen cells was caused by a quantitative rather than a qualitative change in the spleen macrophage population. The possibility that the decline in [14C]TdR uptake into Con A-stimulated TB spleen cells was caused by soluble inhibitory factors in the supernatants from TB spleen cell cultures was excluded.