Induction of Cytotoxic Capacity by Recombinant Gamma Interferon in Human Myelomonocytic Leukaemia Cell Lines

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Abstract
We have investigated the ability of human recombinant gamma interferon (IFN-.gamma.) to induce functional differentiation in three human myelomonocytic cell lines U937, RC2A, and ML-2. Treatment with IFN-.gamma. indcued natural killer (NK) cell like cytotoxicity against K-562 cells in ML-2 and RC2A but not in U937. U937 and RC2A displayed a spontaneous antibody-dependent cell-mediated cytotoxicity (ADCC), which against nucleated target cells was significantly increased in U937 but not in RC2A after treatment with IFN-.gamma.. ML-2 did not display ADCC against nucleated targets either before or after IFN-.gamma. treatment, but lysed efficiently antibody-coated erythrocytes. All three cell lines displayed enhanced ADCC against erythrocytes after IFN-.gamma. treatment. Spontaneous phagocytosis of erythrocytes was seen in U937, and this was enhanced by IFN-.gamma. treatment, while ML-2 and RC2A were phagocytically inactive before and after treatment with IFN-.gamma.. The differentiated functions induced by IFN-.gamma. treatment in this panel of phenotypically closely related cell lines offers an interesting model for further studies on the IFN-.gamma. regulated gene expression. Moreover, the increased cytolytic capacity after exposure to IFN-.gamma. might have implications on the use of IFN-.gamma. for treatment of myelomonocytic malignancies. In such cases, IFN-.gamma. might even increase the aggressiveness of the tumour.