The interferon-gamma receptor in human monocytes is different from the one in nonhematopoietic cells.
The receptor for interferon-gamma (IFN-gamma) on peripheral blood monocytes was characterized and was compared with that of human WISH cells. 125I-IFN-gamma was specifically bound to both cells; however, different binding characteristics were obtained. In the case of monocytes, Scatchard analysis gave an upward concave dependency curve, indicating either multiple binding sites or a negative cooperativity among the binding sites. In contrast, a linear Scatchard plot was obtained for the binding in WISH cells. Competition studies gave even more striking differences. Acid-treated IFN-gamma (95% inactivated) effectively competed with 125I-IFN-gamma for binding to the receptor on WISH cells, but not on monocytes. The significance of these differences was evaluated by analyzing the various biological activities of IFN-gamma in these two cell types. IFN-gamma was found to induce an antiviral state in WISH cells, but not in monocytes. Acid-treated IFN-gamma was found to be almost as active as IFN-gamma itself in inducing HLA-DR in WISH cells, but was almost completely inactive as an HLA-DR inducer in monocytes. It is proposed that these variations in biological activity stem from the presence of different receptors for IFN-gamma in monocytes and in WISH cells. Moreover it is suggested that the immunoregulatory functions of IFN-gamma in monocytes are related to the presence of a distinct IFN-gamma receptor in these cells.
Orchansky
P
P
Rubinstein
M
M
Fischer
D G
DG
D000650:Amnion / Q000166:cytology; D001667:Binding, Competitive; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D011971:Receptors, Immunologic / Q000032:analysis / Q000145:classification* / Q000187:drug effects; D017471:Receptors, Interferon
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D007371:Interferon-gamma