GPI-anchor deficiency in myeloid cells causes impaired FcgammaR effector functions.

Blood
Wouter L W HazenbosTaroh Kinoshita

Abstract

Signaling by transmembrane immunoglobulin G (IgG)-Fc receptors (FcgammaRs) in response to ligand involves association with membrane microdomains that contain glycosyl phosphatidylinositol (GPI)-anchored proteins. Recent in vitro studies showed enhancement of FcgammaR signaling by forced monoclonal antibody-mediated cocrosslinking with various GPI-anchored proteins. Here, the possibility that GPI-anchored proteins are involved in normal physiologic FcgammaR effector functions in response to a model ligand was studied using myeloid-specific GPI-anchor-deficient mice, generated by Cre-loxP conditional targeting. GPI-anchor-deficient primary myeloid cells exhibited normal FcgammaR expression and binding or endocytosis of IgG-immune complexes (IgG-ICs). Strikingly, after stimulation with IgG-ICs, tumor necrosis factor-alpha release, dendritic cell maturation, and antigen presentation were strongly reduced by GPI-anchor deficiency. Tyrosine phosphorylation of the FcR gamma-chain in response to IgG-IC was impaired in GPI-anchor-deficient cells. Myeloid GPI-anchor deficiency resulted in attenuated in vivo inflammatory processes during IgG-IC-mediated alveolitis. This study provides the first genetic evidence for an essential role of GP...Continue Reading

References

Apr 1, 1982·Immunobiology·A Blussé van Oud Alblas, R van Furth
Oct 1, 1981·European Journal of Immunology·J M Austyn, S Gordon
Aug 1, 1996·The Journal of Clinical Investigation·K RajewskyF Schwenk
Jan 20, 1997·The Journal of Experimental Medicine·C WinzlerP Ricciardi-Castagnoli
Jun 5, 1997·Nature·K Simons, E Ikonen
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·M TarutaniJ Takeda
Oct 23, 1997·Journal of Leukocyte Biology·M F GeertsmaP H Nibbering
Jan 7, 1998·The Journal of Cell Biology·J M GreenE J Brown
Apr 1, 1998·Nature·J Banchereau, R M Steinman
Dec 22, 1999·The Journal of Immunology : Official Journal of the American Association of Immunologists·F Y ChuangJ C Unkeless
Jan 6, 2000·Transgenic Research·B E ClausenI Förster
Mar 13, 2001·Annual Review of Immunology·J V Ravetch, S Bolland
Feb 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danita H SchuurhuisFerry Ossendorp
Jun 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hajime KonoZen-ichiro Honda
Nov 5, 2002·Current Opinion in Immunology·P Mark Hogarth
Mar 5, 2003·Annual Review of Immunology·Michelle DykstraSusan K Pierce

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Citations

Apr 20, 2010·Journal of Leukocyte Biology·Marcela RosasPhilip R Taylor
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Aug 28, 2013·Critical Reviews in Biochemistry and Molecular Biology·Dilani G Gamage, Tamara L Hendrickson
Apr 18, 2015·Orphanet Journal of Rare Diseases·Maja Tarailo-GraovacClara D M van Karnebeek
Sep 14, 2007·DNA Sequence : the Journal of DNA Sequencing and Mapping·Dong Hoon Lee, Sang Gu Kang
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jagadeesh BayrySrini V Kaveri
May 11, 2013·Cancer Discovery·Yanli PangLi Yang
Dec 30, 2004·The Journal of Biological Chemistry·Ji Young KangTaroh Kinoshita

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