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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 16, 2008 Accepted May 21, 2008 Deficiency of DAF and Crry on murine platelets leads to complement-dependent clearance via the macrophage phagocytic receptor CRIg David D Kim, Takashi Miwa, Yuko Kimura, Reto A Schwendener, Menno van Lookeren Campagne, and Wen-Chao Song* Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States Institute of Molecular Cancer Research, University Zurich, Zurich, Switzerland Department of Immunology, Genentech, Inc, South San Francisco, CA, United States * Corresponding author; email: song{at}spirit.gcrc.upenn.edu. 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 two 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 the circulation 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 DAF and Crry to be 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 or both failed to prevent Crry-deficient erythrocytes from complement-mediated clearance. These results demonstrate 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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