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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2825-2831. Prepublished online as a Blood First Edition Paper on July 6, 2004; DOI 10.1182/blood-2004-02-0671. This Article Full Text (PDF) All Versions of this Article: 2004-02-0671v1 104/9/2825    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hazenbos, W. L W Articles by Kinoshita, T. Search for Related Content PubMed PubMed Citation Articles by Hazenbos, W. L W Articles by Kinoshita, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2004 Accepted June 14, 2004 GPI-anchor deficiency in myeloid cells causes impaired FcR effector functions Wouter L W Hazenbos, Bjoern E Clausen, Junji Takeda, and Taroh Kinoshita* Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Social and Environmental Medicine, Osaka University Medical School, Osaka, Japan * Corresponding author; email: tkinoshi{at}biken.osaka-u.ac.jp. Signaling by transmembrane IgG-Fc receptors (FcR) in response to ligand involves association with membrane microdomains containing GPI-anchored proteins. Recent in vitro studies showed enhancement of FcR signaling by forced monoclonal antibody-mediated co-crosslinking with various glycosyl phosphatidylinositol (GPI)-anchored proteins. Here, the possibility that GPI-anchored proteins are involved in normal physiological FcR effector functions in response to natural ligand was studied using myeloid-specific GPI-anchor deficient mice, generated by Cre-loxP conditional targeting. GPI anchor-deficient primary myeloid cells exhibited normal FcR expression and binding or endocytosis of model IgG-immune complexes (IgG-IC). Strikingly, after stimulation with IgG-IC, tumor necrosis factor-a release, dendritic cell maturation and antigen presentation were strongly reduced by GPI anchor-deficiency. Tyrosine phosphorylation of the FcR -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 GPI-anchored proteins in physiological FcR effector functions in vitro and in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Bayry, S. Lacroix-Desmazes, M. D. Kazatchkine, O. Hermine, D. F. Tough, and S. V. Kaveri Modulation of Dendritic Cell Maturation and Function by B Lymphocytes J. Immunol., July 1, 2005; 175(1): 15 - 20. [Abstract] [Full Text] [PDF] J. Y. Kang, Y. Hong, H. Ashida, N. Shishioh, Y. Murakami, Y. S. Morita, Y. Maeda, and T. Kinoshita PIG-V Involved in Transferring the Second Mannose in Glycosylphosphatidylinositol J. Biol. Chem., March 11, 2005; 280(10): 9489 - 9497. [Abstract] [Full Text] [PDF]

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