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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1109-1119. Prepublished online as a Blood First Edition Paper on June 4, 2008; DOI 10.1182/blood-2008-01-134304. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-134304v1 112/4/1109    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Kim, D. D. Articles by Song, W.-C. Search for Related Content PubMed PubMed Citation Articles by Kim, D. D. Articles by Song, W.-C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Deficiency of decay-accelerating factor and complement receptor 1–related gene/protein y on murine platelets leads to complement-dependent clearance by the macrophage phagocytic receptor CRIg David D. Kim1, Takashi Miwa1, Yuko Kimura1, Reto A. Schwendener2, Menno van Lookeren Campagne3, and Wen-Chao Song1 1 Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA; 2 Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland; and 3 Department of Immunology, Genentech, South San Francisco, CA Complement activation on human platelets is known to cause platelet degranulation and activation. To evaluate how normal platelets escape complement attack in vivo, we studied the fate of murine platelets deficient in 2 membrane complement regulatory proteins using an adoptive transfer model. We show here that deficiency of either decay-accelerating factor (DAF) or complement receptor 1–related gene/protein y (Crry) on murine platelets was inconsequential, whereas DAF and Crry double deficiency led to rapid clearance of platelets from circu-lation in a complement- and macrophage-dependent manner. This finding contrasted with the observation on erythrocytes, where Crry deficiency alone resulted in complement susceptibility. Quantitative flow cytometry revealed that DAF and Crry were expressed at similar levels on platelets, whereas Crry expression was 3 times higher than DAF on erythrocytes. Antibody blocking or gene ablation of the newly identified complement receptor CRIg, but not complement receptor 3 (CR3), rescued DAF/Crry-deficient platelets from complement-dependent elimination. Surprisingly, deficiency of CRIg, CR3, and other known complement receptors failed to prevent Crry-deficient erythrocytes from complement-mediated clearance. These results show a critical but redundant role of DAF and Crry in platelet survival and suggest that complement-opsonized platelets and erythrocytes engage different complement receptors on tissue macrophages in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Miwa, L. Zhou, Y. Kimura, D. Kim, A. Bhandoola, and W.-C. Song Complement-dependent T-cell lymphopenia caused by thymocyte deletion of the membrane complement regulator Crry Blood, March 19, 2009; 113(12): 2684 - 2694. [Abstract] [Full Text] [PDF] N. N. Gorgani, J. Q. He, K. J. Katschke Jr., K. Y. Helmy, H. Xi, M. Steffek, P. E. Hass, and M. van Lookeren Campagne Complement Receptor of the Ig Superfamily Enhances Complement-Mediated Phagocytosis in a Subpopulation of Tissue Resident Macrophages J. Immunol., December 1, 2008; 181(11): 7902 - 7908. [Abstract] [Full Text] [PDF]

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