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Blood First Edition Paper, prepublished online November 6, 2009; DOI 10.1182/blood-2009-07-235150. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 CrossRef Google Scholar Articles by Bridges, D. J. Articles by Craig, A. PubMed PubMed Citation Articles by Bridges, D. J. Articles by Craig, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 27, 2009; accepted October 8, 2009. Rapid activation of endothelial cells enables P. falciparum adhesion to platelet decorated von Willebrand factor strings Daniel J. Bridges1,6, James Bunn2, Jan A. van Mourik3, Georges Grau4, Roger J.S. Preston5, Malcolm Molyneux2, Valery Combes4, James S. O'Donnell5, Bas de Laat3 and Alister Craig1 1 Liverpool School of Tropical Medicine, Liverpool; 2 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; 3 Sanquin Blood Supply Foundation, Amsterdam, Netherlands; 4 Dept. Pathology, Faculty of Medicine, University of Sydney, Australia; 5 Haemostasis Research Group, Trinity Centre for Health Sciences, Trinity College Dublin, Ireland * Corresponding author; email: d.bridges{at}liverpool.ac.uk Abstract During Plasmodium falciparum malaria infections, von Willebrand factor (VWF) levels are elevated, post-mortem studies show platelets co-localised with sequestered infected erythrocytes (IE) at brain microvascular sites, while in vitro studies have demonstrated platelet-mediated IE adhesion to TNF-activated brain endothelium via a bridging mechanism. This current study demonstrates how all these observations could be linked through a completely novel mechanism whereby IE adhere via platelet decorated ultra-large VWF strings on activated endothelium. Using an in vitro laminar flow model, we have demonstrated tethering and firm adhesion of IE to the endothelium specifically at sites of platelet accumulation. We also show that an IE pro-adhesive state, capable of supporting high levels of binding within minutes of induction can be removed through the action of the VWF protease ADAMTS-13. We propose that this new mechanism contributes to sequestration both independently of and in concert with current adhesion mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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