Interferon-gamma enhances target cell sensitivity to monocyte killing.
The mechanism of human peripheral blood monocyte-mediated cytotoxicity was investigated using the HT-29 human colon adenocarcinoma line, A673 human rhabdomyosarcoma line, and A375 human melanoma line as target cells. Pretreatment of these target cells with 100 U/ml of recombinant human interferon (IFN)-gamma for 48 hr increased their susceptibility to monocyte killing. Increased susceptibility to the lytic action was particularly pronounced at low effector/target cell ratios. Unlike IFN-gamma human IFN-alpha did not potentiate monocyte cytotoxicity, and pretreatment of HT-29 with IFN-alpha also had virtually no effect on their susceptibility to monocyte killing. However, IFN-gamma appeared to prime either monocytes or target cells to become responsive to IFN-alpha. Our data suggest that IFN-gamma can promote the killing of tumor cells by monocytes through two separate actions, one on the monocyte and one on the target cell.
D000230:Adenocarcinoma; D002460:Cell Line; D003110:Colonic Neoplasms; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008545:Melanoma; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012208:Rhabdomyosarcoma
D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma