Differential role of neutrophil Fcγ receptor IIIb (CD16) in phagocytosis, bacterial killing, and responses to immune complexes

被引:81
作者
Fossati, G
Moots, RJ
Bucknall, RC
Edwards, SW
机构
[1] Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England
[2] Univ Hosp Aintree, Liverpool, Merseyside, England
[3] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England
来源
ARTHRITIS AND RHEUMATISM | 2002年 / 46卷 / 05期
关键词
D O I
10.1002/art.10230
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 a 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. Conclusion. 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 serumopsonized 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.
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页码:1351 / 1361
页数:11
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