Stimulation of Differentiation of Mouse Myeloid Leukemic Cells and Induction of Interferon in the Cells by Double-stranded Polyribonucleotides1

Mouse myeloid leukemic Ml cells can be induced to differ entiate into mature macrophages and granulocytes by differ entiation-stimulating factor (D-factor) in conditioned medium of mouse peritoneal macrophages. Double-stranded RNA's, such as the copolymers of polyinosinic and polycytidylic acids and polyadenylic and polyuridylic acids, could not alone induce differentiation of the cells, but enhanced induction of differen tiation by low concentrations of the D-factor and induced a significant amount of interferon. Rabbit antiserum to purified Lcell interferon neutralized the antiviral activity of interferon of Ml cells. Simultaneous treatment of Ml cells with the antiinterferon serum and copolymer of polyinosine and polycyti dylic acids and D-factor abolished the enhancing effect of copolymer of polyinosine and polycytidylic acids on the action of the D-factor. These results suggest that the effect of doublestranded RNA's on induction of differentiation of Ml cells is mediated by interferon produced by the cells.