The production of immunoregulatory factors by a human macrophage-like cell line: I. Characterization of an inhibitor of lymphocyte DNA synthesis

Stimulation of the human histiocytic lymphoma, U937, with the lectins concanavalin A or phytohemagglutinin, results in the production of an inhibitor of mitogen-induced peripheral blood lymphocyte proliferation. This inhibitor of DNA synthesis (IDS) has an apparent molecular weight of ~65,000, is heat (56 °C) and acid (pH 2.0) labile, but is resistant to 10 −4 M 2-mercaptoethanol treatment. The mechanism of action is nontoxic and reversible within 24 hr of removal of the cells from IDS-containing supernatants. A variety of lymphoid and lymphoblastoid cell lines of B and T lymphocyte origin are sensitive to the effects of IDS. In contrast, the nonlymphoid cell lines HeLa, L929, MCF-7, and T47-D are unaffected by exposures to high concentrations of IDS preparations. The relationship of the IDS to other macrophage-derived inhibitory factors is discussed.