Storm, Janet, Jespersen, Jakob S, Seydel, Karl B, Szestak, Tadge, Mbewe, Maurice, Chisala, Ngawina V, Phula, Patricia, Wang, Christian W, Taylor, Terrie E, Moxon, Christopher A et al (show 2 more authors)
(2019)
Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.
EMBO MOLECULAR MEDICINE, 11 (2).
e9164-.
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Abstract
Sequestration of <i>Plasmodium falciparum</i>-infected erythrocytes (IE) within the brain microvasculature is a hallmark of cerebral malaria (CM). Using a microchannel flow adhesion assay with TNF-activated primary human microvascular endothelial cells, we demonstrate that IE isolated from Malawian paediatric CM cases showed increased binding to brain microvascular endothelial cells compared to IE from uncomplicated malaria (UM) cases. Further, UM isolates showed significantly greater adhesion to dermal than to brain microvascular endothelial cells. The major mediator of parasite adhesion is <i>P. falciparum</i> erythrocyte membrane protein 1, encoded by <i>var</i> genes. Higher levels of <i>var</i> gene transcripts predicted to bind host endothelial protein C receptor (EPCR) and ICAM-1 were detected in CM isolates. These data provide further evidence for differential tissue binding in severe and uncomplicated malaria syndromes, and give additional support to the hypothesis that CM pathology is based on increased cytoadherence of IE in the brain microvasculature.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | cerebral malaria, cytoadherence, paediatric patient isolates, PfEMP1, Plasmodium falciparum |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 13 May 2019 10:11 |
| Last Modified: | 14 Feb 2024 08:52 |
| DOI: | 10.15252/emmm.201809164 |
| Open Access URL: | http://embomolmed.embopress.org/content/11/2/e9164 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3041028 |
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