Conditioned medium (CM) from lectin-stimulated human leukocytes contains factors that induce human promyelocytic cell lines to differentiate along the monocytic pathway. In this report, we show that human promyelocytic cell lines are also induced to differentiate along this pathway by immune interferon (IFN gamma). Various preparations of IFN alpha tested did not induce this differentiation. In cultures containing IFN gamma, the cells are induced to coordinately express monocyte markers and functions such as monocyte-specific surface antigens, HLA-DR antigens, nonspecific esterase, receptors for the Fc fragment of IgG, and the ability to mediate antibody-dependent cell- mediated cytotoxicity. Our data indicate that differentiation induced by IFN gamma is not secondary to an arrest of growth of promyelocytic cell lines, but rather that a proportion of cells is induced along a programmed pathway of terminal differentiation similar to that of normal monocytes. CM contains IFN gamma, but its ability to induce differentiation is greater than expected on the basis of its content of IFN gamma. Treatments at 56 degrees C or at pH 2.0, which abolish IFN gamma activity, abrogate the differentiation ability of CM. The antiviral activity and the differentiation activity contained in the CM are coeluted from gel filtration and reverse-phase columns. Monoclonal antibodies anti-IFN gamma, which completely abrogate the differentiation ability of IFN gamma and the antiviral activity in the CM, completely suppress the induction of some monocyte markers by CM, but only reduce the expression of others. When IFN gamma is added to CM, promyelocytic cell lines are induced to differentiate to a much greater extent than that induced by either IFN gamma or IFN gamma- depleted CM alone. These results show that the differentiation activity of leukocyte CM is due to the synergistic effect of IFN gamma and other factors not yet identified.

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