Natural resistance of mice to transplants of foreign bone marrow or leukemia cells is mediated by radioresistant non-T effectors which may interact with accessory macrophage-like cells sensitive to the toxicity of silica particles. The role of the accessory cells was reinvestigated by means of the soluble antimacrophage agent Seakem-9 carrageenan, and for comparison with silica particles. The agents abrogated or weakened resistance to parental, allogeneic, and xenogeneic rat marrow grafts when a single relatively small dose (2 mg/mouse or less) was injected intravenously into irradiated mice, 5 to 24 hr after transplantation. This effect was dose dependent, not influenced by the sex of recipients and donors and, unlike the effect of silica particles, not prevented by the previous injection into the mice of the lysosomal stabilizer (i.e., macrophage protector) poly-2-vinylpyridine N-oxide. This discrepancy raised the possibility that carrageenan weakened resistance by impairing the function of cells other than macrophages, whereas silica particles did so by way of selective macrophage depletion. However, the combined effect of suboptimal doses of carrageenan and silica particles was additive, a result which favors the view that carrageenan functioned as an anti-macrophage agent in vivo. These experiments reiterate the importance of macrophage-like cells interacting with radioresistant non-T cells (presumably null lymphocytes) in the development of natural cell-mediated responses such as resistance to hemopoietic grafts and generation of killer cells for certain lymphomas.

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This work was supported by NIH Research Grants AM-13969 and CA-12844, and by Contract NO1-CM-53766 from the Division of Cancer Treatment, National Cancer Institute.

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