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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5046-5051. Prepublished online as a Blood First Edition Paper on September 10, 2008; DOI 10.1182/blood-2008-06-164350. This Article Full Text (PDF) All Versions of this Article: blood-2008-06-164350v1 112/13/5046    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Van Den Broeck, T. Articles by Leclercq, G. Search for Related Content PubMed PubMed Citation Articles by Van Den Broeck, T. Articles by Leclercq, G. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 20, 2008 Accepted August 10, 2008 Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator Tina Van Den Broeck, Frederik Stevenaert, Sylvie Taveirne, Veronique Debacker, Christel Vangestel, Bart Vandekerckhove, Tom Taghon, Patrick Matthys, Jean Plum, Werner Held, Mieke Dewerchin, Wayne M. Yokoyama, and Georges Leclercq* Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium Laboratory of Immunology, Katholieke Universiteit Leuven, Leuven, Belgium Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland Center for Transgene Technology and Gene Therapy, Katholieke Universiteit Leuven, Leuven, Belgium Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, United States * Corresponding author; email: georges.leclercq{at}ugent.be. The Ly49 natural killer (NK) cell receptor family comprises both activating and inhibitory members, which recognize major histocompatibility complex (MHC) class I or MHC class I-related molecules and are involved in target recognition. As previously shown, the Ly49E receptor fails to bind to a variety of soluble or cell-bound MHC class I molecules, indicating that its ligand is not an MHC class I molecule. Using BWZ.36 reporter cells, we demonstrate triggering of Ly49E by the completely distinct, non-MHC-related protein urokinase plasminogen activator (uPA). uPA is known to be secreted by a variety of cells, including epithelial and hematopoietic cells and levels are upregulated during tissue remodeling, infections and tumorigenesis. Here we show that addition of uPA to Ly49E-positive adult and fetal NK cells inhibits interferon- secretion and reduces their cytotoxic potential, respectively. These uPA-mediated effects are Ly49E-dependent, as they are reversed by addition of anti-Ly49E monoclonal antibody and by downregulation of Ly49E expression using RNA interference. Our results suggest that uPA, besides its established role in fibrinolysis, tissue remodeling and tumor metastasis, could be involved in NK cell mediated immune surveillance and tumor escape. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Ly49 receptors: not always a class I act? Colin G. Brooks Blood 2008 112: 4789-4790. [Full Text] [PDF]

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