Cerebral malaria is associated with differential cytoadherence to brain endothelial cells
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Cerebral malaria is associated with differential cytoadherence to brain endothelial cells. / 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.; Lavstsen, Thomas; Craig, Alister G.
I: EMBO Molecular Medicine, Bind 2019, Nr. 11, e9164, 2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Cerebral malaria is associated with differential cytoadherence to brain endothelial cells
AU - Storm, Janet
AU - Jespersen, Jakob S.
AU - Seydel, Karl B.
AU - Szestak, Tadge
AU - Mbewe, Maurice
AU - Chisala, Ngawina V.
AU - Phula, Patricia
AU - Wang, Christian W.
AU - Taylor, Terrie E.
AU - Moxon, Christopher A.
AU - Lavstsen, Thomas
AU - Craig, Alister G.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - cerebral malaria
KW - cytoadherence
KW - paediatric patient isolates
KW - PfEMP1
KW - Plasmodium falciparum
U2 - 10.15252/emmm.201809164
DO - 10.15252/emmm.201809164
M3 - Journal article
C2 - 30610112
AN - SCOPUS:85059522343
VL - 2019
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 11
M1 - e9164
ER -
ID: 212853298