Regulation of macrophage Fc receptor expression and phagocytosis by histidine-rich glycoprotein.
Regulation of macrophage Fc receptor (Fc gamma R)-mediated phagocytic function by histidine-rich glycoprotein (HRG) was investigated. Pretreatment of oil-elicited inflammatory mouse peritoneal macrophages with HRG for 1-3 hr increased their Fc gamma R-mediated binding and phagocytosis of IgG-opsonized sheep erythrocyte conjugates (EA). A significant reduction of Fc gamma R-dependent EA binding and phagocytosis occurred after pretreatment of macrophages with HRG for more than 8 hr. These results indicate that HRG is capable of modulating Fc gamma R expression in a biphasic fashion, which directly affects the overall efficiency of phagocytosis. HRG differentially regulated the functions of Fc gamma R subclasses. For example, HRG reduced the efficiency of Fc gamma RII (Fc gamma 2b/gamma 1R)-dependent phagocytosis of erythrocytes conjugated with monoclonal IgG2b or IgG1 by macrophages pretreated with HRG for 24 hr. However, when similar studies were performed using erythrocytes coated with monoclonal IgG2a, HRG was less effective in inhibiting Fc gamma RI (Fc gamma 2aR)-dependent phagocytosis. As an HRG-binding glycosaminoglycan, heparin failed to block the regulatory function of HRG on macrophages. Similarly, interferon-gamma (IFN-gamma) was not capable of blocking the functional activity of HRG. These studies suggest that HRG regulates macrophage function via a novel pathway different from that of heparin or IFN-gamma.
Chang
N S
NS
Guthrie Research Institute, Laboratory of Molecular Immunology, Guthrie Medical Center, Sayre, Pennsylvania 18840.
Leu
R W
RW
Rummage
J A
JA
Anderson
J K
JK
Mole
J E
JE
D000818:Animals; D006493:Heparin / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000276:immunology*; D011506:Proteins / Q000276:immunology* / Q000302:isolation & purification; D017452:Receptors, IgG / Q000032:analysis*; D000099053:Histidine-Rich Glycoprotein
D007074:Immunoglobulin G; D011506:Proteins; D017452:Receptors, IgG; D000099053:Histidine-Rich Glycoprotein; D007371:Interferon-gamma; D006493:Heparin