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 Blood, 15 April 2008, Vol. 111, No. 8, pp. 4096-4105.
Prepublished online as a Blood First Edition Paper on December 21, 2007; DOI 10.1182/blood-2007-05-089565.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Gas6 promotes inflammation by enhancing interactions between endothelial cells, platelets, and leukocytes

Marc Tjwa1,2, Lola Bellido-Martin3, Yuan Lin4, Esther Lutgens5, Stéphane Plaisance1,2, Françoise Bono6, Nathalie Delesque-Touchard6, Caroline Hervé6, Rute Moura7, An D. Billiau4, Cristina Aparicio3,8, Marcel Levi1,2, Mat Daemen5, Mieke Dewerchin1,2, Florea Lupu9, Jef Arnout7, Jean-Marc Herbert6, Mark Waer4, Pablo García de Frutos3,8, Björn Dahlbäck8, Peter Carmeliet1,2, Marc F. Hoylaerts7, and Lieve Moons1,2

1 Department of Transgene Technology and Gene Therapy, Flanders Institute of Biotechnology (VIB), Leuven, Belgium; 2 Center of Transgene Technology and Gene Therapy, Katholieke Universiteit (KU) Leuven, Leuven, Belgium; 3 Instituto de Investigaciones Biomédicas de Barcelona (IIBB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)–Consejo Superior de Investigaciones Cientificas (CSIC), Barcelona, Spain; 4 Laboratory of Experimental Transplantation, KU Leuven, Leuven, Belgium; 5 Department of Pathology, University of Maastricht, Masstricht, The Netherlands; 6 Cardiovascular-Thrombosis Research Department, Sanofi-Aventis, Toulouse, France; 7 Center of Molecular and Vascular Biology, KU Leuven, Leuven, Belgium; 8 Department of Clinical Chemistry, University of Lund, Malmo, Sweden; and 9 Cardiovascular Research Program, Oklahoma Medical Research Foundation, Oklahoma City

The role of Gas6 in endothelial cell (EC) function remains incompletely characterized. Here we report that Gas6 amplifies EC activation in response to inflammatory stimuli in vitro. In vivo, Gas6 promotes and accelerates the sequestration of circulating platelets and leukocytes on activated endothelium as well as the formation and endothelial sequestration of circulating platelet-leukocyte conjugates. In addition, Gas6 promotes leukocyte extravasation, inflammation, and thrombosis in mouse models of inflammation (endotoxinemia, vasculitis, heart transplantation). Thus, Gas6 amplifies EC activation, thereby playing a key role in enhancing the interactions between ECs, platelets, and leukocytes during inflammation.


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Gas6 inflames cell interactions
Delphine Borgel
Blood 2008 111: 3915. [Full Text] [PDF]



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