Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.
EMBO Mol Med
; 11(2)2019 02.
Article
in En
| MEDLINE
| ID: mdl-30610112
ABSTRACT
Sequestration of Plasmodium falciparum-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 P. falciparum erythrocyte membrane protein 1, encoded by var genes. Higher levels of var 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Brain
/
Cell Adhesion
/
Malaria, Cerebral
/
Endothelial Cells
/
Erythrocytes
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Year:
2019
Type:
Article