Induction of cytotoxic capacity by recombinant gamma interferon in human myelomonocytic leukaemia cell lines.
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 induced 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.
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology*; D012397:Rosette Formation
D011961:Receptors, Fc; D011994:Recombinant Proteins; D007371:Interferon-gamma