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Blood, 15 January 2007, Vol. 109, No. 2, pp. 610-612. Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-05-022756. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-05-022756v1 109/2/610    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 Dasgupta, S. Articles by Lacroix-Desmazes, S. Search for Related Content PubMed PubMed Citation Articles by Dasgupta, S. Articles by Lacroix-Desmazes, S. Related Collections Brief Reports Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors Suryasarathi Dasgupta1,2, Yohann Repessé1,3, Jagadeesh Bayry1,2, Ana-Maria Navarrete1,2, Bharath Wootla1,2, Sandrine Delignat1,2, Theano Irinopoulou2,4, Caroline Kamaté5, Jean-Marie Saint-Remy6, Marc Jacquemin6, Peter J. Lenting5, Annie Borel-Derlon3, Srinivas V. Kaveri1,2, and Sébastien Lacroix-Desmazes1,2, 1 Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 681, Paris, France; 2 Université Pierre et Marie Curie–Paris 6, Institut des Cordeliers, Institut Fédératif de Recherche (IFR) 58, and Institut du Fer a Moulin, IFR 83, Paris, France; 3 Université de Caen, Laboratoire d'hématologie Equipe d'Accueil (EA) 3212, Caen, France; 4 INSERM, U536, U706, Paris, France; 5 Laboratory for Thrombosis and Haemostasis, Department of Hematology, University Medical Center, Utrecht, The Netherlands; 6 Center for Molecular and Vascular Biology, University of Leuven, Belgium Von Willebrand factor (VWF) is a chaperone molecule for procoagulant factor VIII (FVIII). Its role in the reduction of the immunogenicity of therapeutic FVIII in patients with hemophilia A has been evoked but lacks clear cellular and molecular rationale. Here, we demonstrate that VWF protects FVIII from being endocytosed by human dendritic cells (DCs) and subsequently presented to FVIII-specific T cells. The immunoprotective effect of VWF requires a physical interaction with FVIII because the endocytosis of FVIII was significantly restored on hindering the formation of the VWF-FVIII complex. Interestingly, VWF had no direct inhibitory effect either on the ability of DCs to present antigenic peptides or on the activation potency of CD4+ T cells. We thus propose that VWF may reduce the immunogenicity of FVIII by preventing, upstream from the activation of immune effectors, the entry of FVIII in professional antigen-presenting cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Dasgupta, A. M. Navarrete, S. Andre, B. Wootla, S. Delignat, Y. Repesse, J. Bayry, A. Nicoletti, E. L. Saenko, R. d'Oiron, et al. Factor VIII bypasses CD91/LRP for endocytosis by dendritic cells leading to T-cell activation Haematologica, January 1, 2008; 93(1): 83 - 89. [Abstract] [Full Text] [PDF] S. Delignat, S. Dasgupta, S. Andre, A.-M. Navarrete, S. V. Kaveri, J. Bayry, M.-H. Andre, S. Chtourou, Z. Tellier, and S. Lacroix-Desmazes Comparison of the immunogenicity of different therapeutic preparations of human factor VIII in the murine model of hemophilia A Haematologica, October 1, 2007; 92(10): 1423 - 1426. [Abstract] [Full Text] [PDF] T. Calvez, Y. Laurian, and J. Goudemand Associations between type of product and inhibitors in previously untreated patients (PUPs) with severe hemophilia: switches and particular products can disturb analysis Blood, August 1, 2007; 110(3): 1073 - 1074. [Full Text] [PDF] S. Dasgupta, A.-M. Navarrete, J. Bayry, S. Delignat, B. Wootla, S. Andre, O. Christophe, M. Nascimbeni, M. Jacquemin, L. Martinez-Pomares, et al. A role for exposed mannosylations in presentation of human therapeutic self-proteins to CD4+ T lymphocytes PNAS, May 22, 2007; 104(21): 8965 - 8970. [Abstract] [Full Text] [PDF]

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