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

Daniel J. Bridges*, James E. G. Bunn, Jan A. van Mourik, Georges Grau, Roger J. S. Preston, Malcolm E. Molyneux, Valery Combes, James S. O'Donnell, Bas de Laat, Alister G. Craig

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)1472-1474
JournalBlood
Volume115
Issue number7
DOIs
Publication statusPublished - 18 Feb 2010

Fingerprint

Dive into the research topics of 'Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings'. Together they form a unique fingerprint.

Cite this