Interferon-gamma treatment impairs Fc receptor type II-mediated phagocytosis of human macrophages by a post-receptor-binding mechanism.
The influence of priming by interferon-gamma (IFN-gamma) on FcR expression and function was investigated with human monocyte-derived macrophages. As a ligand specifically interacting with FcRII, bovine IgG1-coated erythrocytes (Bo1-EA) were used. The uptake of these particles by human monocytes and macrophages could be inhibited with anti-FcRII. Moreover, macrophages representing the phenotype that fails to interact with murine IgG1, as revealed in an anti-CD3 IgG1-driven T-cell proliferation assay, had a low avidity for Bo1-EA, and Bo1-EA-macrophage interaction could not be inhibited by anti-FcRII in these cells. Thus, anti-Leu-4 non-responsiveness in a T-cell stimulation assay is associated with an inability of FcRII to interact with bovine IgG1. An influence of IFN-gamma priming on FcRII expression and function was studied, therefore, in anti-Leu-4 responders (bovine IgG1 high responders in the phagocytosis test, susceptible to anti-FcRII treatment). IFN-gamma-primed macrophages from such donors displayed a markedly reduced phagocytosis of Bo1-EA. This reduction was observed both with adherent and with suspended macrophages This type of modulation was not due to a reduced expression of FcRII, nor due to a reduced avidity of expressed FcR to its ligand, as revealed by flow cytometric and rosetting analysis. Since phagocytosis of latex particles and of tanned erythrocytes is little influenced by IFN-gamma priming, our data suggest that IFN-gamma affects FcRII-mediated phagocytosis by a post-receptor-binding mechanism.
Jungi
T W
TW
Institute of Veterinary Virology, University of Berne, Switzerland.
Brcic
M
M
Leutwyler
C
C
Pfister
H
H
Spycher
M O
MO
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010587:Phagocytosis / Q000276:immunology*; D017452:Receptors, IgG; D011994:Recombinant Proteins
D015703:Antigens, CD; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011994:Recombinant Proteins; D007371:Interferon-gamma