ROLE OF IMMUNE INTERFERON IN THE MONOCYTIC DIFFERENTIATION OF HUMAN PROMYELOCYTIC CELL-LINES INDUCED BY LEUKOCYTE CONDITIONED MEDIUM

  • 1 January 1985
    • journal article
    • research article
    • Vol. 66  (3) , 583-594
Abstract
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 cells 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 cells 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 IFNY, but its ability to induce differentiation is greater than expected on the basis of its content of IFN.gamma.. Treatments at 56.degree. 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 cells 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.