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Role of immune interferon in the monocytic differentiation of human
promyelocytic cell lines induced by leukocyte conditioned medium
ET Dayton, M Matsumoto-Kobayashi, B Perussia and G Trinchieri
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.
Volume 66,
Issue 3,
pp. 583-594,
09/01/1985
Copyright © 1985 by The American Society of Hematology
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