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Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings.

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Bridges, Daniel J, Bunn, J., van Mourik, Jan A, Grau, Georges, Preston, Roger J S, Molyneux, Malcolm E, Combes, Valery, O'Donnell, James S, de Laat, Bas and Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 (2010) 'Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings.'. Blood, Vol 115, Issue 7, pp. 1472-4.

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Abstract

During Plasmodium falciparum malaria infections, von Willebrand factor (VWF) levels are elevated, postmortem studies show platelets colocalized with sequestered infected erythrocytes (IEs) at brain microvascular sites, whereas in vitro studies have demonstrated platelet-mediated IE adhesion to tumor necrosis factor-activated brain endothelium via a bridging mechanism. This current study demonstrates how all these observations could be linked through a completely novel mechanism whereby IEs 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 IEs 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 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). We propose that this new mechanism contributes to sequestration both independently of and in concert with current adhesion mechanisms.

Item Type: Article
Additional Information: Published in final edited form as: Blood. 2010 February 18; 115(7): 1472–1474. doi:10.1182/blood-2009-07-235150.
Uncontrolled Keywords: VWF; malaria; adhesion; P. falciparum; platelets
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 300 Blood platelets
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1182/blood-2009-07-235150
Depositing User: Mary Creegan
Date Deposited: 14 Jun 2010 08:33
Last Modified: 17 Jul 2020 10:57
URI: https://archive.lstmed.ac.uk/id/eprint/1013

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