ArticleCellular microbiology2015
Diverse functional outcomes of Plasmodium falciparum ligation of EPCR: potential implications for malarial pathogenesis.
Article in Cellular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
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- Hemostatic and protein C pathway dysfunction in the pathogenesis of experimental cerebral malaria.Haematologica · 2022Article
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- Determinants of brain swelling in pediatric and adult cerebral malaria.JCI insight · 2021Article
- Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes.PLoS pathogens · 2021Article
- Malaria link of hypertension: a hidden syndicate of angiotensin II, bradykinin and sphingosine 1-phosphate.Human cell · 2021Review
- Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood-brain barrier in cerebral malaria.The Journal of experimental medicine · 2021Article
- Congenital Transmission of Apicomplexan Parasites: A Review.Frontiers in microbiology · 2021Review
- PfEMP1 A-Type ICAM-1-Binding Domains Are Not Associated with Cerebral Malaria in Beninese Children.mBio · 2020Article
- Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro.Malaria journal · 2020Article
- Mediterranean Diet: Lipids, Inflammation, and Malaria Infection.International journal of molecular sciences · 2020Review
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- Testing the effect of PAR1 inhibitors onWellcome open research · 2020Article
- Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries.Science advances · 2020Article
- Interplay of Plasmodium falciparum and thrombin in brain endothelial barrier disruption.Scientific reports · 2019Article
- Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Plasmodium falciparum-infected erythrocytes (IRBC) expressing the domain cassettes (DC) 8 and 13 of the cytoadherent ligand P. falciparum erythrocyte membrane protein 1 adhere to the endothelial protein C receptor (EPCR). By interfering with EPCR anti-coagulant and pro-endothelial barrier functions, IRBC adhesion could promote coagulation and vascular permeability that contribute to the pathogenesis of cerebral malaria. In this study, we examined the adhesion of DC8- and DC13-expressing parasite lines to endothelial cells from different microvasculature, and the consequences of EPCR engagement on endothelial cell function. We found that IRBC from IT4var19 (DC8) and IT4var07 (DC13) parasite lines adhered to human brain, lung and dermal endothelial cells under shear stress. However, the relative contribution of EPCR to parasite cytoadherence on different types of endothelial cell varied. We also observed divergent functional outcomes for DC8 cysteine-rich interdomain region (CIDR)α1.1 and DC13 CIDRα1.4 domains. IT4var07 CIDRα1.4 inhibited generation of activated protein C (APC) on lung and dermal endothelial cells and blocked the APC-EPCR binding interaction on brain endothelial cells. IT4var19 CIDRα1.1 inhibited thrombin-induced endothelial barrier dysfunction in lung endothelial cells, whereas IT4var07 CIDRα1.4 inhibited the protective effect of APC on thrombin-induced permeability. Overall, these findings reveal a much greater complexity of how CIDRα1-expressing parasites may modulate malaria pathogenesis through EPCR adhesion.
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