Effects of human fibroblast (β) or leukocyte (α) interferon (IFN) on differentiations of a human histiocytic lymphoma-derived cell line (U937) or promyelocytic leukemia-derived cell line (HL-60) were studied. When cultured with β-IFN (400-1,000 U/ml). U937 cells showed gross morphologic and microscopic changes consisting of clumping, increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, and membrane ruffling. After culture with β-IFN, the number of U937 cells reactive with B43.4.1 monoclonal antibody, which is specific for human monocytes, natural killer cells, and neutrophils, increased from <10% of U937 cells to 47%. β-IFN treatment also enhanced antibody-dependent cellular cytotoxicity against chicken erythrocytes by U937 cells. The same morphologic, phenotypic, and functional changes were also observed when U937 were treated with recombinant or natural α-IFN. The effects of α-IFN were totally abolished by anti-α-IFN serum. In contrast, HL-60, which differentiates toward cells of the monocyte lineage in response to phorbol 12-myristate 13-acetate (based on the above criteria), and toward granulocytes in response to dimethyl sulfoxide, did not differentiate when cultured with α- or β-IFN. No consistent relationship between induction of differentiation and changes in phospholipid methylation were observed.
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