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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4149-4158. Prepublished online as a Blood First Edition Paper on February 2, 2006; DOI 10.1182/blood-2005-09-3808. This Article Full Text (PDF) All Versions of this Article: 2005-09-3808v1 107/10/4149    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 Vachon, E. Articles by Downey, G. P Search for Related Content PubMed PubMed Citation Articles by Vachon, E. Articles by Downey, G. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 22, 2005 Accepted January 12, 2006 CD44 is a Phagocytic Receptor Eric Vachon, Raiza Martin, Jonathan D Plumb, Vivian Kwok, R. William Vandivier, Michael Glogauer, Andras Kapus, Xiaomin Wang, Chung-Wai Chow, Sergio Grinstein, and Gregory P Downey* Department of Medicine, Division of Respirology, University of Toronto, Toronto, Ontario, Canada Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Colorado, Denver, CO, USA CIHR Group in Matrix Dynamics, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada Research Institute, Toronto General Hospital of the University Health Network, Toronto, Ontario, Canada Department of Medicine, Division of Respirology, University of Toronto, Toronto, Ontario, Canada; Research Institute, Toronto General Hospital of the University Health Network, Toronto, Ontario, Canada * Corresponding author; email: gregory.downey{at}utoronto.ca. CD44, a transmembrane adhesion molecule involved in binding and metabolism of hyaluronan, has additional functions in inflammatory and immune responses, contributing to the ingestion and clearance of particles and apoptotic cells. Our goal was to determine the specific role of CD44 in phagocytosis and whether it functions as a primary or accessory phagocytic receptor. Using hyaluronan-coated beads and erythrocytes coated with anti-CD44 antibodies as the phagocytic prey, we determined that CD44 mediates efficient phagocytosis in primary murine peritoneal macrophages and in the murine macrophage cell line RAW 264.7. In RAW cells, the phagocytic index for anti-CD44-coated erythrocytes was 25 ± 3 (mean ± SEM) compared to < 1 for erythrocytes coated with isotype-matched control antibodies. Uptake of anti-CD44-coated erythrocytes was abrogated by pre-treatment with a blocking antibody to CD44 and was absent in primary cultures of CD44-deficient murine macrophages. Down-regulation of Fc receptors by aggregated IgG-induced internalization, which blocks uptake of IgG-coated particles, had no effect on CD44-mediated particle engulfment. Using a combination of immunoprecipitation, pharmacological inhibition and genetic deletion, we determined that CD44-mediated phagocytosis involves Syk, Rac1, and phosphatidylinositol 3-kinase and induced activation of the phagocyte oxidase. We conclude that CD44 is a competent phagocytic receptor that efficiently mediates internalization of large particles. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Huebener, T. Abou-Khamis, P. Zymek, M. Bujak, X. Ying, K. Chatila, S. Haudek, G. Thakker, and N. G. Frangogiannis CD44 Is Critically Involved in Infarct Healing by Regulating the Inflammatory and Fibrotic Response J. Immunol., February 15, 2008; 180(4): 2625 - 2633. [Abstract] [Full Text] [PDF] C. Lau, X. Wang, L. Song, M. North, S. Wiehler, D. Proud, and C.-W. Chow Syk Associates with Clathrin and Mediates Phosphatidylinositol 3-Kinase Activation during Human Rhinovirus Internalization J. Immunol., January 15, 2008; 180(2): 870 - 880. [Abstract] [Full Text] [PDF] E. Vachon, R. Martin, V. Kwok, V. Cherepanov, C.-W. Chow, C. M. Doerschuk, J. Plumb, S. Grinstein, and G. P. Downey CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages Blood, December 15, 2007; 110(13): 4492 - 4502. [Abstract] [Full Text] [PDF] S. Garantziotis, J. W. Hollingsworth, R. B. Ghanayem, S. Timberlake, L. Zhuo, K. Kimata, and D. A. Schwartz Inter-{alpha}-Trypsin Inhibitor Attenuates Complement Activation and Complement-Induced Lung Injury J. Immunol., September 15, 2007; 179(6): 4187 - 4192. [Abstract] [Full Text] [PDF] A. M. Miller, M. J. Nolan, J. Choi, T. Koga, X. Shen, B. Y. J. T. Yue, and P. A. Knepper Lactate Treatment Causes NF-{kappa}B Activation and CD44 Shedding in Cultured Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1615 - 1621. [Abstract] [Full Text] [PDF] X. Zhu, M. S. Chang, R. C. Hsueh, R. Taussig, K. D. Smith, M. I. Simon, and S. Choi Dual Ligand Stimulation of RAW 264.7 Cells Uncovers Feedback Mechanisms That Regulate TLR-Mediated Gene Expression J. Immunol., October 1, 2006; 177(7): 4299 - 4310. [Abstract] [Full Text] [PDF]

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