Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.

Storm, Janet ORCID: https://orcid.org/0000-0001-7812-4220, Jespersen, Jakob S, Seydel, Karl B, Szestak, Tadge, Mbewe, Maurice, Chisala, Ngawina V, Phula, Patricia, Wang, Christian W, Taylor, Terrie E, Moxon, Christopher A, Lavstsen, Thomas and Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 (2019) 'Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.'. EMBO Molecular Medicine, Issue e9164.

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Abstract

Sequestration of -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 erythrocyte membrane protein 1, encoded by genes. Higher levels of 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
Subjects:	QS Anatomy > Histology > QS 532.5.E7 Epithelium QX Parasitology > Protozoa > QX 135 Plasmodia WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.15252/emmm.201809164
Depositing User:	Stacy Murtagh
Date Deposited:	07 Jan 2019 11:13
Last Modified:	17 Jul 2019 14:15
URI:	https://archive.lstmed.ac.uk/id/eprint/9935

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