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Blood, 1 February 2006, Vol. 107, No. 3, pp. 955-964. Prepublished online as a Blood First Edition Paper on October 4, 2005; DOI 10.1182/blood-2004-12-4856. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4856v1 107/3/955    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 Bonnefoy, A. Articles by Hoylaerts, M. F. Search for Related Content PubMed PubMed Citation Articles by Bonnefoy, A. Articles by Hoylaerts, M. F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13 Arnaud Bonnefoy, Kim Daenens, Hendrik B. Feys, Rita De Vos, Petra Vandervoort, Jos Vermylen, Jack Lawler, and Marc F. Hoylaerts From the Center for Molecular and Vascular Biology, Laboratory of Morphology and Molecular Pathology, and Laboratory for Thrombosis Research, Interdisciplinary Research Center, Campus Kortrijk, University of Leuven, Belgium; Department of Pathology, Harvard Medical School, Boston, MA; INSERM, U 553; Institut de Formation et de Recherche (IFR) 105, Institut d'Hématologie; and Université Paris VII Denis Diderot, Paris, France. The function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1-/- mice, via dynamic platelet interaction studies with A23187 [GenBank] -stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187 [GenBank] -stimulated blood vessels of WT mice, but Tsp1-/- platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1-/- vessels only. Stimulation generated temporary endothelium-associated ultralarge von Willebrand factor (VWF) multimers, triggering platelet string formation in 48% of WT versus 20% of Tsp1-/- vessels. Injection of human TSP-1 or thrombotic thrombocytopenic purpura (TTP) patient-derived neutralizing anti-ADAMTS13 antibodies corrected the defective platelet recruitment in Tsp1-/- mice, while having a moderate effect in WT mice. Photochemical injury of intestinal blood vessels induced thrombotic occlusions with longer occlusion times in Tsp1-/- venules (1027 ± 377 seconds) and arterioles (858 ± 289 seconds) than in WT vessels (559 ± 241 seconds, P < .001; 443 ± 413 seconds, P < .003) due to defective thrombus adherence, resulting in embolization of complete thrombi, a defect restored by both human TSP-1 and anti-ADAMTS13 antibodies. We conclude that in a shear field, soluble or local platelet-released TSP-1 can protect unfolded endothelium-bound and subendothelial VWF from degradation by plasma ADAMTS13, thus securing platelet tethering and thrombus adherence to inflamed and injured endothelium, respectively. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Liu, P. Garg, S. Yang, P. Gong, M. A. Pallero, D. S. Annis, Y. Liu, A. Passaniti, D. Mann, D. F. Mosher, et al. 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