SEARCH:   Advanced

Blood, 1 February 2005, Vol. 105, No. 3, pp. 1085-1093. Prepublished online as a Blood First Edition Paper on September 23, 2004; DOI 10.1182/blood-2004-03-1101. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1101v1 105/3/1085    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 Crawley, J. T. B. Articles by Lane, D. A. Search for Related Content PubMed PubMed Citation Articles by Crawley, J. T. B. Articles by Lane, D. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Proteolytic inactivation of ADAMTS13 by thrombin and plasmin James T. B. Crawley, Jonathan K. Lam, James B. Rance, Luigina R. Mollica, James S. O'Donnell, and David A. Lane From the Haematology Department, Division of Investigative Sciences, Faculty of Medicine, Imperial College London, United Kingdom. The multimeric size and the function of circulating von Willebrand factor are modulated via its proteolytic cleavage by the plasma metalloproteinase, ADAMTS13. It is unclear how ADAMTS13 activity is regulated within the vascular system. In the absence of a regulatory mechanism, ADAMTS13 activity might compromise platelet adhesion at sites of vascular injury. We hypothesized that at sites of vascular injury, ADAMTS13 activity could be regulated locally by coagulation proteinases. Initiation of coagulation in human plasma resulted in the disappearance of added full-length recombinant ADAMTS13. This loss was inhibited by hirudin. Using purified proteins, we showed that ADAMTS13 is proteolyzed at several cleavage sites by thrombin in a time- and concentration-dependent manner. Furthermore, this proteolysis ablated ADAMTS13 activity against purified von Willebrand factor. Preincubation of thrombin with soluble thrombomodulin, but not heparin, inhibited the proteolysis of ADAMTS13, suggesting the involvement of thrombin exosite I (and not exosite II) in ADAMTS13 recognition. Plasmin also cleaved ADAMTS13 into similar fragments, resulting in the loss of ADAMTS13 activity. This study demonstrates the susceptibility of ADAMTS13 to proteolytic inactivation and suggests possible roles for thrombin and plasmin at sites of vascular injury. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Down-regulation of ADAMTS13 activity by serine proteases Yoshihiro Fujimura Blood 2005 105: 911-912. [Full Text] [PDF] This article has been cited by other articles: S. Zanardelli, A. C. K. Chion, E. Groot, P. J. Lenting, T. A. J. McKinnon, M. A. Laffan, M. Tseng, and D. A. Lane A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF Blood, September 24, 2009; 114(13): 2819 - 2828. [Abstract] [Full Text] [PDF] R. de Groot, A. Bardhan, N. Ramroop, D. A. Lane, and J. T. B. Crawley Essential role of the disintegrin-like domain in ADAMTS13 function Blood, May 28, 2009; 113(22): 5609 - 5616. [Abstract] [Full Text] [PDF] Q. de Mast, E. Groot, P. B. Asih, D. Syafruddin, M. Oosting, S. Sebastian, B. Ferwerda, M. G. Netea, P. G. de Groot, A. J. A. M. van der Ven, et al. ADAMTS13 Deficiency with Elevated Levels of Ultra-Large and Active von Willebrand Factor in P. falciparum and P. vivax Malaria Am J Trop Med Hyg, March 1, 2009; 80(3): 492 - 498. [Abstract] [Full Text] [PDF] M. D. Gardner, C. K. N. K. Chion, R. de Groot, A. Shah, J. T. B. Crawley, and D. A. Lane A functional calcium-binding site in the metalloprotease domain of ADAMTS13 Blood, January 29, 2009; 113(5): 1149 - 1157. [Abstract] [Full Text] [PDF] B. Ponnuchamy and R. A. Khalil Role of ADAMs in Endothelial Cell Permeability: Cadherin Shedding and Leukocyte Rolling Circ. Res., May 23, 2008; 102(10): 1139 - 1142. [Full Text] [PDF] M.-C. Chung, T. G. Popova, S. C. Jorgensen, L. Dong, V. Chandhoke, C. L. Bailey, and S. G. Popov Degradation of Circulating von Willebrand Factor and Its Regulator ADAMTS13 Implicates Secreted Bacillus anthracis Metalloproteases in Anthrax Consumptive Coagulopathy J. Biol. Chem., April 11, 2008; 283(15): 9531 - 9542. [Abstract] [Full Text] [PDF] J. Song, K. A Lee, T. S. Park, R. Park, and J. R. Choi Linear Relationship between ADAMTS13 Activity and Platelet Dynamics Even Before Severe Thrombocytopenia Ann. Clin. Lab. Sci., January 1, 2008; 38(4): 368 - 375. [Abstract] [Full Text] [PDF] K. K. Swisher, J. T. Doan, S. K. Vesely, H. C. Kwaan, B. Kim, B. Lammle, J. A. Kremer Hovinga, and J. N. George Pancreatitis preceding acute episodes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: report of five patients with a systematic review of published reports Haematologica, July 1, 2007; 92(7): 936 - 943. [Abstract] [Full Text] [PDF] S. Ferrari, F. Scheiflinger, M. Rieger, G. Mudde, M. Wolf, P. Coppo, J.-P. Girma, E. Azoulay, C. Brun-Buisson, F. Fakhouri, et al. Prognostic value of anti-ADAMTS13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS13 activity Blood, April 1, 2007; 109(7): 2815 - 2822. [Abstract] [Full Text] [PDF] C. K. N. K. Chion, C. J. M. Doggen, J. T. B. Crawley, D. A. Lane, and F. R. Rosendaal ADAMTS13 and von Willebrand factor and the risk of myocardial infarction in men Blood, March 1, 2007; 109(5): 1998 - 2000. [Abstract] [Full Text] [PDF] T. C. Nguyen, A. Liu, L. Liu, C. Ball, H. Choi, W. S. May, K. Aboulfatova, A. L. Bergeron, and J.-f. Dong Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis Haematologica, January 1, 2007; 92(1): 121 - 124. [Abstract] [Full Text] [PDF] E. R. Guinto, N. Grafos, D. G. Motto, and R. S. Greenfield Recombinant ADAMTS13 Processing by FXIa Is Distinct from Thrombin. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 4041 - 4041. [Abstract] [PDF] T. E. Adams and J. A. Huntington Thrombin-Cofactor Interactions: Structural Insights Into Regulatory Mechanisms Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1738 - 1745. [Abstract] [Full Text] [PDF] A. K. Chauhan, D. G. Motto, C. B. Lamb, W. Bergmeier, M. Dockal, B. Plaimauer, F. Scheiflinger, D. Ginsburg, and D. D. Wagner Systemic antithrombotic effects of ADAMTS13 J. Exp. Med., March 20, 2006; 203(3): 767 - 776. [Abstract] [Full Text] [PDF] S. Zanardelli, J. T. B. Crawley, C. K. N. C. K. Chion, J. K. Lam, R. J. S. Preston, and D. A. Lane ADAMTS13 Substrate Recognition of von Willebrand Factor A2 Domain J. Biol. Chem., January 20, 2006; 281(3): 1555 - 1563. [Abstract] [Full Text] [PDF] T. Ono, J. Mimuro, S. Madoiwa, K. Soejima, Y. Kashiwakura, A. Ishiwata, K. Takano, T. Ohmori, and Y. Sakata Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure Blood, January 15, 2006; 107(2): 528 - 534. [Abstract] [Full Text] [PDF] D. A. Lane, H. Philippou, and J. A. Huntington Directing thrombin Blood, October 15, 2005; 106(8): 2605 - 2612. [Abstract] [Full Text] [PDF] J. S. O'Donnell, T. A. J. McKinnon, J. T. B. Crawley, D. A. Lane, and M. A. Laffan Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis Blood, September 15, 2005; 106(6): 1988 - 1991. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020