SEARCH:   Advanced

Blood, 15 December 2007, Vol. 110, No. 13, pp. 4492-4502. Prepublished online as a Blood First Edition Paper on September 7, 2007; DOI 10.1182/blood-2007-02-076539. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-076539v1 110/13/4492    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 February 23, 2007 Accepted August 29, 2007 CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages Eric Vachon, Raiza Martin, Vivian Kwok, Vera Cherepanov, Chung-Wai Chow, Claire M. Doerschuk, Jonathan Plumb, Sergio Grinstein, and Gregory P. Downey* Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada Toronto General Hospital Research Institute of the University Health Network, Toronto, Ontario, Canada Division of Integrative Biology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States Department of Cellular Biology, Research Institute of the Hospital for Sick Children, Toronto, Ontario, Canada * Corresponding author; email: downeyg{at}njc.org. Diverse receptors including Fc receptors and 2 integrins (CR3, CD11b/CD18) have been implicated in phagocytosis but their distinct roles and interactions with other receptors in particle engulfment are not well defined. CD44, a transmembrane adhesion molecule involved in binding and metabolism of hyaluronan, may have additional functions in regulation of inflammation and phagocytosis. We have recently reported that CD44 is a fully competent phagocytic receptor that is able to trigger ingestion of large particles by macrophages. Here we investigated the role of co-receptors and intracellular signalling pathways in modulation of CD44-mediated phagocytosis. Using biotinylated erythrocytes coated with specific antibodies (Ebabs) as the phagocytic prey, we determined that CD44-mediated phagocytosis is reduced by 45% by a blocking CD11b antibody. Further, CD44-mediated phagocytosis was substantially (42%) reduced in CD18 null mice. Immunofluorescence microscopy revealed that CD11b is recruited to the phagocytic cup. The mechanism of integrin activation and mobilization involved activation of the GTPase Rap1. CD44-mediated phagocytosis was also sensitive to the extracellular concentration of the divalent cation Mg2+ but not Ca2+. Additionally, buffering of intracellular Ca2+ did not affect CD44-mediated phagocytosis. Taken together, these data suggest that CD44 stimulation induces inside-out activation of CR3 through the GTPase Rap1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Zen, D.-Q. Liu, L.-M. Li, C. X.-J. Chen, Y.-L. Guo, B. Ha, X. Chen, C.-Y. Zhang, and Y. Liu The Heparan Sulfate Proteoglycan Form of Epithelial CD44v3 Serves as a CD11b/CD18 Counter-receptor during Polymorphonuclear Leukocyte Transepithelial Migration J. Biol. Chem., February 6, 2009; 284(6): 3768 - 3776. [Abstract] [Full Text] [PDF] Y. Miyake, M. Sakurai, S. Tanaka, W. A. S. Tunjung, M. Yokoo, H. Matsumoto, H. Aso, T. Yamaguchi, and E. Sato Expression of Hyaluronan Synthase 1 and Distribution of Hyaluronan During Follicular Atresia in Pig Ovaries Biol Reprod, February 1, 2009; 80(2): 249 - 257. [Abstract] [Full Text] [PDF] A. G. Dupuy and E. Caron Integrin-dependent phagocytosis - spreading from microadhesion to new concepts J. Cell Sci., June 1, 2008; 121(11): 1773 - 1783. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020