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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2832-2839. Prepublished online as a Blood First Edition Paper on December 5, 2006; DOI 10.1182/blood-2006-06-032524. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-06-032524v1 109/7/2832    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 Othman, M. Articles by Lillicrap, D. Search for Related Content PubMed PubMed Citation Articles by Othman, M. Articles by Lillicrap, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance Maha Othman1, Andrea Labelle1, Ian Mazzetti1, Hisham S. Elbatarny2, and David Lillicrap1 1 Department of Pathology and Molecular Medicine and 2 Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, Canada Thrombocytopenia has been consistently reported following the administration of adenoviral gene transfer vectors. The mechanism underlying this phenomenon is currently unknown. In this study, we have assessed the influence of von Willebrand Factor (VWF) and P-selectin on the clearance of platelets following adenovirus administration. In mice, thrombocytopenia occurs between 5 and 24 hours after adenovirus delivery. The virus activates platelets and induces platelet-leukocyte aggregate formation. There is an associated increase in platelet and leukocyte-derived microparticles. Adenovirus-induced endothelial cell activation was shown by VCAM-1 expression on virus-treated, cultured endothelial cells and by the release of ultra-large molecular weight multimers of VWF within 1 to 2 hours of virus administration with an accompanying elevation of endothelial microparticles. In contrast, VWF knockout (KO) mice did not show significant thrombocytopenia after adenovirus administration. We have also shown that adenovirus interferes with adhesion of platelets to a fibronectin-coated surface and flow cytometry revealed the presence of the Coxsackie adenovirus receptor on the platelet surface. We conclude that VWF and P-selectin are critically involved in a complex platelet-leukocyte-endothelial interplay, resulting in platelet activation and accelerated platelet clearance following adenovirus administration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. V. Shashkova, K. Doronin, J. S. Senac, and M. A. Barry Macrophage Depletion Combined with Anticoagulant Therapy Increases Therapeutic Window of Systemic Treatment with Oncolytic Adenovirus Cancer Res., July 15, 2008; 68(14): 5896 - 5904. [Abstract] [Full Text] [PDF] X. Huang, L. Zhuang, Y. Cao, Q. Gao, Z. Han, D. Tang, H. Xing, W. Wang, Y. Lu, G. Xu, et al. Biodistribution and kinetics of the novel selective oncolytic adenovirus M1 after systemic administration Mol. Cancer Ther., June 1, 2008; 7(6): 1624 - 1632. [Abstract] [Full Text] [PDF] D. Stone, Y. Liu, D. Shayakhmetov, Z.-Y. Li, S. Ni, and A. Lieber Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver J. Virol., May 1, 2007; 81(9): 4866 - 4871. [Abstract] [Full Text] [PDF]

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