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Blood, 1 January 2006, Vol. 107, No. 1, pp. 135-142. Prepublished online as a Blood First Edition Paper on September 6, 2005; DOI 10.1182/blood-2005-03-1312. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-03-1312v1 107/1/135    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 Qi, J. C. Articles by Krilis, S. A. Search for Related Content PubMed PubMed Citation Articles by Qi, J. C. Articles by Krilis, S. A. Related Collections Cell Adhesion and Motility Signal Transduction Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor Jian C. Qi, Jing Wang, Sravan Mandadi, Kumiko Tanaka, Basil D. Roufogalis, Michele C. Madigan, Kenneth Lai, Feng Yan, Beng H. Chong, Richard L. Stevens, and Steven A. Krilis From the Department of Medicine, University of New South Wales, and Department of Immunology, Allergy and Infectious Diseases, St George Hospital, New South Wales, Australia; the Faculty of Pharmacy, University of Sydney, New South Wales, Australia; the Department of Clinical Ophthalmology, Save Sight Institute, Sydney Eye Hospital, New South Wales, Australia; the Department of Medicine, University of New South Wales, and the Department of Haematology, St George Hospital, New South Wales, Australia; and the Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA. Interleukin-16 (IL-16) induces the chemotaxis and activation of mast cells (MCs) and other cell types. While it has been concluded that CD4 is the primary IL-16 receptor on T cells, at least one other IL-16 receptor exists. We now show that the IL-16–responsive human MC line HMC-1 lacks CD4, and that the IL-16–mediated chemotactic and Ca2+ mobilization responses of this cell can be blocked by anti-CD9 monoclonal antibodies (mAbs) but not by mAbs directed against CD4 or other tetraspanins. Anti-CD9 mAbs also inhibited the IL-16–mediated activation of nontransformed human cord blood–derived MCs and mouse bone marrow–derived MCs by 50% to 60%. The chemotactic response of HMC-1 cells to IL-16, as well as the binding of the cytokine to the cell's plasma membrane, was inhibited by CD9-specific antisense oligonucleotides. CD9 is therefore essential for the IL-16–mediated chemotaxis and activation of the HMC-1 cell line. In support of this conclusion, IL-16 bound to CD9-expressing CHO cell transfectants. The ability of wortmannin and xestopongin C to inhibit the IL-16–mediated chemotactic response of these cells suggests that the cytokine activates a phosphatidylinositol 3-kinase (PI3K)/inositol trisphosphate–dependent signaling pathway in MCs. This is the first report of a tetraspanin that plays a prominent role in a cytokine-mediated chemotactic response of human MCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mast cells: must they always be different? Hovav Nechushtan and Ehud Razin Blood 2006 107: 1-2. [Full Text] [PDF] This article has been cited by other articles: G. Min, H. Wang, T.-T. Sun, and X.-P. Kong Structural basis for tetraspanin functions as revealed by the cryo-EM structure of uroplakin complexes at 6-A resolution J. Cell Biol., June 19, 2006; 173(6): 975 - 983. [Abstract] [Full Text] [PDF]

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