Relationships between suppressor macrophages and macrophage precursors in the spleens from tumor-bearing mice

Suppressor macrophages (Mφ) which can inhibit mitogen-induced lymphocyte proliferation appeared in the spleens of mice bearing transplanted MC-A fibrosarcoma cells. An analysis of the ontogeny of such Mφ revealed additional suppressor activity directed against macrophage stem cells. Treatment of spleen cell suspensions with carbonyl iron followed by centrifugation removed suppressor Mφ but did not deplete Mφ-colony forming cells (M-CFC) which could be demonstrated in soft agar culture in L-cell conditioned medium (LCM). Untreated spleen cells had normal numbers of M-CFC; phagocyte-depleted mononuclear cells showed a threefold increase in M-CFC 14 days after subcutaneous inoculation of 10⁶ MC-A cells per mouse. Further increases in M-CFC were also evident in similar preparations on Days 21 and 28 when the M-CFC concentration reached a maximum of eight times the normal level. The Mφ which developed from the M-CFC grown in the presence of LCM were later shown to have indomethacin-sensitive suppressor activity suggesting the mediation of this phenomenon by prostaglandins. These observations suggest that locally produced phagocytic suppressor Mφ from the spleens of tumorbearing mice play important roles not only as inhibitors of lymphocyte proliferation as reported earlier, but also as regulators of monocyte-Mφ production.