Effect of rIFN-gamma on antibody-mediated cytotoxicity via human monocyte IgG Fc receptor II (CD32).
Human monocytes and macrophages express an isoform of IgG Fc receptor II (Fc gamma RII), Fc gamma RIIa. Two allotypic variants of this receptor could be distinguished with respect to their ability to bind murine (m)IgG1 complexes either strongly or weakly, defined as high-responder (HR) and low-responder (LR), respectively. We investigated the effect of recombinant (r)IFN-gamma on the ability of freshly isolated monocytes, and those cultured for 40 h and 9 days, to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Using human erythrocytes (E) sensitized with mIgG1 as target cells, Fc gamma RII was studied selectively. Cells which had been cultured for 40 h exhibit a significantly decreased Fc gamma RII expression, and Fc gamma RII-mediated ADCC activity as compared with freshly isolated monocytes. Co-culture with rIFN-gamma (40 h) reversed this decrease. Short-term rIFN-gamma-cultured cells, and fresh cells express similar numbers of Fc gamma RII, and exhibit comparable Fc gamma RII-mediated ADCC activity. Phagocytic activity was not affected. Prolonged culture of monocytes for 9 days, co-cultured with rIFN-gamma either from day 0 or from day 7, did not affect expression or functional activity of Fc gamma RII. Furthermore, the effects were observed in both HR and LR individuals. Our results show that rIFN-gamma has strong effects on Fc gamma RII-mediated responses specifically during the early stages of monocyte maturation, most likely by affecting receptor expression levels.
van Schie
R C
RC
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Verstraten
H G
HG
Tax
W J
WJ
van den Berkmortel
F W
FW
van de Winkel
J G
JG
de Mulder
P H
PH
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D017452:Receptors, IgG; D011994:Recombinant Proteins
D015703:Antigens, CD; D006684:HLA-DR Antigens; D017452:Receptors, IgG; D011994:Recombinant Proteins; D007371:Interferon-gamma