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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings
Blood, Volume 115, No. 7, Year 2010
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Description
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. © 2010 by The American Society of Hematology.
Authors & Co-Authors
Bridges, Daniel J.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Bunn, James Edward G.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Malawi, Zomba
University of Malawi
van Mourik, Jan A.
Netherlands, Amsterdam
Stichting Sanquin Bloedvoorziening
Grau, Georges Emile Raymond
Australia, Sydney
Faculty of Medicine and Health
Preston, Roger J.S.
Ireland, Dublin
Trinity College Dublin
Molyneux, Malcolm Edward
Malawi, Zomba
University of Malawi
Combes, Valery
Australia, Sydney
Faculty of Medicine and Health
O'Donnell, James S.
Ireland, Dublin
Trinity College Dublin
de Laat, Bas
Netherlands, Amsterdam
Stichting Sanquin Bloedvoorziening
Craig, Alister Gordon
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Statistics
Citations: 120
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1182/blood-2009-07-235150
ISSN:
00064971
Research Areas
Cancer
Infectious Diseases