ArticleCellular microbiology2015
Plasmodium falciparum adhesion domains linked to severe malaria differ in blockade of endothelial protein C receptor.
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 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Meta-analysis of Plasmodium falciparummBio · 2019Pooled it
- Structural vulnerability in EPCR suggests functional modulation.Scientific reports · 2024Article
- Probing cerebral malaria inflammation in 3D human brain microvessels.Cell reports · 2023Article
- International Center of Excellence for Malaria Research for South Asia and Broader Malaria Research in India.The American journal of tropical medicine and hygiene · 2022Article
- Diverse Malaria Presentations across National Institutes of Health South Asia International Center for Excellence in Malaria Research Sites in India.The American journal of tropical medicine and hygiene · 2022Article
- Identification of a broad lipid repertoire associated to the endothelial cell protein C receptor (EPCR).Scientific reports · 2022Article
- Article
- Determinants of brain swelling in pediatric and adult cerebral malaria.JCI insight · 2021Article
- Review
- 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
- Interplay of Plasmodium falciparum and thrombin in brain endothelial barrier disruption.Scientific reports · 2019Article
- Article
- Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.EMBO molecular medicine · 2019Article
- Endothelial Protein C Receptor Could Contribute to Experimental Malaria-Associated Acute Respiratory Distress Syndrome.Journal of immunology research · 2019Article
- Opportunities for Host-targeted Therapies for Malaria.Trends in parasitology · 2018Review
- Elimination of intravascular thrombi prevents early mortality and reduces gliosis in hyper-inflammatory experimental cerebral malaria.Journal of neuroinflammation · 2018Article
- Endothelial cell protein C receptor-dependent signaling.Current opinion in hematology · 2018Review
- Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in EPCR-binding function.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Cytoadhesion of Plasmodium falciparum-infected erythrocytes to endothelial protein C receptor (EPCR) is associated with severe malaria. It has been postulated that parasite binding could exacerbate microvascular coagulation and endothelial dysfunction in cerebral malaria by impairing the protein C-EPCR interaction, but the extent of binding inhibition has not been fully determined. Here we expressed the cysteine-rich interdomain region (CIDRα1) domain from a variety of domain cassette (DC) 8 and DC13 P. falciparum erythrocyte membrane protein 1 proteins and show they interact in a distinct manner with EPCR resulting in weak, moderate and strong inhibition of the activated protein C (APC)-EPCR interaction. Overall, there was a positive correlation between CIDRα1-EPCR binding activity and APC blockade activity. In addition, our analysis from a combination of mutagenesis and blocking antibodies finds that an Arg81 (R81) in EPCR plays a pivotal role in CIDRα1 binding, but domains with weak and strong APC blockade activity were distinguished by their sensitivity to inhibition by anti-EPCR mAb 1535, implying subtle differences in their binding footprints. These data reveal a previously unknown functional heterogeneity in the interaction between P. falciparum and EPCR and have major implications for understanding the distinct clinical pathologies of cerebral malaria and developing new treatment strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.