Differential role of neutrophil Fcgamma receptor IIIB (CD16) in phagocytosis, bacterial killing, and responses to immune complexes.
OBJECTIVE
To determine the roles played by the neutrophil Fcgamma receptor type II (FcgammaRII) (CD32) and FcgammaRIIIb (CD16) in phagocytosis, bacterial killing, and activation by immune complexes (ICs) and to test the hypothesis that inhibition of pathologic effector neutrophil function is possible without compromising host defense.


METHODS
Receptor function was probed by enzymic removal of FcgammaRIIIb from the cell surface and by use of Fab/F(ab')(2) fragments of monoclonal antibodies to block receptor-ligand binding. Cells were challenged with (a) serum-opsonized Staphylococcus aureus, (b) serum- and IgG-opsonized latex particles, and (c) synthetic soluble and insoluble ICs to mimic bacterial and inflammatory stimuli.


RESULTS
Phosphatidylinositol-phospholipase C treatment removed >97% of surface FcgammaRIIIb from neutrophils previously treated with tumor necrosis factor alpha to mobilize intracellular stores of receptor. This treatment profoundly inhibited activation of primed neutrophils by soluble ICs of the type found in diseased rheumatoid joints, but had no effect on phagocytosis and killing of serum-opsonized S aureus.


CONCLUSIONS
FcgammaRIIIb plays a major role in the secretion of toxic products in response to ICs, but little or no role in the phagocytosis and killing of serum-opsonized bacteria. The selective suppression of effector neutrophil function is therefore possible. FcgammaRIIIb, or its intracellular signaling pathway, is a potential therapeutic target in inflammatory diseases such as rheumatoid arthritis, because disruption of its function should decrease inflammatory tissue damage, but not jeopardize host protection against infection.
Fossati
Gianluca
G
University of Liverpool, Liverpool, UK.
Moots
Robert J
RJ
Bucknall
Roger C
RC
Edwards
Steven W
SW
D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000382:microbiology; D001798:Blood Proteins / Q000276:immunology; D058851:GPI-Linked Proteins; D006358:Hot Temperature; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology; D008863:Microspheres; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D016897:Respiratory Burst / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D001798:Blood Proteins; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG