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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 31, 2005 Accepted July 5, 2005 Human and Mouse Mast Cells Use the Tetraspanin CD9 as an Alternate Interleukin 16 Receptor Jian Cheng Qi, Jing Wang, Sravan Mandadi, Kumiko Tanaka, Basil D Roufogalis, Michele C Madigan, Kenneth Lai, Feng Yan, Beng H Chong, Richard L Steven, and Steven A Krilis* Department of Medicine, Department of Immunology, Allergy & Infectious Disease, St. George Hospital, University of New South Wales, Sydney, New South Wales, Australia Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia Department of Clinical Ophthalmology, Save Sight Institute, Sydney Eye Hospital, Sydney, New South Wales, Australia Department of Medicine, Department of Haematology, St. George Hospital, University of New South Wales, Sydney, New South Wales, Australia Department of Medicine, Harvard Medical School & Brigham & Women's Hospital, Boston, Massachusetts, USA * Corresponding author; email: s.krilis{at}unsw.edu.au. Interleukin (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 non-transformed human cord blood-derived MCs and mouse bone marrow-derived MCs by 50-60%. The chemotactic response of HMC-1 cells to IL-16, as well as the binding of the cytokine to the cell's plasma membrane, were 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 signalling 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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