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Effect of Endogenous and Exogenous Interferons on the Differentiation of Human Monocyte Cell Line U937¹

INSERM, Unité 245 et Centre National de la Recherche Scientifique, U.A.C. 113, Center INSERM, Hôpital St-Antoine, 184, rue du Faubourg St-Antoine, 75571 Paris Cédex 12, France; INSERM, Unité 91, Hôpital Henri Mondor, 51, avenue du Maréchal de Lattre de Tassigny, 94010 Creteil, France; and Instituto Superiore di Sanita, Laboratorio di Ematologia, Viale Regina Elena, 299-00161 Roma, Italy

The effect of interferons (IFNs) on the differentiation of hematopoietic cells was examined with the human monocyte cell line U937. The differentiation of U937 was induced by hydroxyvitamin D₃ and was evaluated through the study of specific markers.

The induction of the U937 differentiation was associated with a production of IFN and with a marked increase in (2'5') oligoadenylate synthetase. Addition of anti-IFN-/ß antibodies inhibited the enhancement of (2'5') oligoadenylate synthetase and reduced the inhibitory effect of hydroxyvitamin D₃ on cell growth. Nevertheless, neutralization of endogenous IFN excreted during U937 cell maturation did not modify the expression of the differentiation markers examined. Exogenous natural IFN-, IFN-ß, or recombinant (r) IFN-, when added to the culture medium, did not promote a "global" U937 differentiation. Most of the differentiation markers, except for reduction of nitroblue-tetrazolium, were not induced by IFN- or -ß. However, rIFN- was able to induce the appearance of several monocytic membrane markers at an extent comparable or slightly inferior to that elicited by hydroxyvitamin D₃. Different effects on the expression of HLA antigens were obtained with these IFNs: IFN- or -ß enhanced mainly class I HLA antigen expression, whereas rIFN- increased selectively the expression of class II HLA DC1 but not HLA DR antigens. In contrast, phytohemagglutinin-leukocyte conditioned medium elicited a marked and selective enhancement of the expression of HLA-DR antigens. This induction of HLA DC1 antigens by rIFN- was not observed in two other leukemic cell lines (HL60 and HEL). The present study shows that IFN- or -ß may participate in the antiproliferative effect occurring during cellular differentiation, while IFN- may be involved in the induction of the expression of specific monocytic markers involved in cellular immunoregulation.

¹ This research was supported in part by grants from INSERM (U.245, U.91), Centre National de la Recherche Scientifique (U.A.C. 113), Fondation pour la Recherche Médicale, and Associazione Italiana per la Ricerca sul Cancro.

² To whom requests for reprints should be addressed, at U.245 INSERM, Centre INSERM, Hôpital St-Antoine, 184, rue du Faubourg St-Antoine, 75571 Paris Cédex 12, France.

Received 3/17/87. Revised 9/14/87. Accepted 9/30/87.