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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 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 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 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  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator Tina Van Den Broeck1,*, Frederik Stevenaert1,*, Sylvie Taveirne1, Veronique Debacker1, Christel Vangestel1, Bart Vandekerckhove1, Tom Taghon1, Patrick Matthys2, Jean Plum1, Werner Held3, Mieke Dewerchin4, Wayne M. Yokoyama5, and Georges Leclercq1 1 Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium; 2 Laboratory of Immunology, Katholieke Universiteit Leuven, Leuven, Belgium; 3 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; 4 Center for Transgene Technology and Gene Therapy, Katholieke Universiteit Leuven, Leuven, Belgium; and 5 Division of Rheumatology, Washington University School of Medicine, St Louis, MO 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 up-regulated 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 down-regulation 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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