MONOCYTIC DIFFERENTIATION MODULATES APOPTOTIC RESPONSE TO CYTOTOXIC ANTI-FAS ANTIBODY AND TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN MONOBLAST U937 CELLS

Interferon-gamma (IFN-gamma), vitamin D-3 (VD), and retinoic acid (RA) induce differentiation of human monoblastic leukemia U937 cells to ma crophage-like cells with potential superoxide anion-generating activit y upon further stimulation. Here we report that U937 cells thus differ entiated show various responses to apoptotic induction with a cytotoxi c anti-Fas antibody and tumor necrosis factor (TNF), VD-or RA-treated U937 cells acquired resistance against Fas- or TNF receptor (TNFR)-med iated apoptosis, whereas apoptotic cell death was accelerated in IFN-g amma-treated cells, By flow cytometric analyses, no decrease in expres sion of surface Fas antigen or p55 TNFR was observed in differentiated U937 cells, Cell surface expression of CD11b was seen only when diffe rentiation was induced with VD or RA but not with IFN-gamma, The growt h of VD- or RA-treated cells was retarded but IFN-gamma-treated cells were prolific, These findings suggest that the differentiation state d iffers with the inducer and that the cellular response to apoptotic in duction is closely related to the state including the cell cycle.