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Severe malaria is associated with parasite binding to endothelial protein C receptor.

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Title: Severe malaria is associated with parasite binding to endothelial protein C receptor.
Authors: Turner, Louise, Lavstsen, Thomas, Berger, Sanne S., Wang, Christian W., Petersen, Jens E. V., Avril, Marion, Brazier, Andrew J., Freeth, Jim, Jespersen, Jakob S., Nielsen, Morten A., Magistrado, Pamela, Lusingu, John, Smith, Joseph D., Higgins, Matthew K., Theander, Thor G.
Source: Nature. 6/27/2013, Vol. 498 Issue 7455, p502-505. 4p. 1 Diagram, 1 Chart, 1 Graph.
Subjects: Malaria, Endothelial cells, Protein C, Plasmodium falciparum, Erythrocytes, Juvenile diseases, Membrane proteins, Gene expression
Abstract: Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year. Sequestration is mediated by specific interactions between members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins was unknown. Here we identify endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C, as the endothelial receptor for DC8 and DC13 PfEMP1. We show that EPCR binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDRα1) of DC8 and group A PfEMP1 subfamilies, and that CIDRα1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways, and has implications for understanding malaria pathology and the development of new malaria interventions. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Severe malaria is associated with parasite binding to endothelial protein C receptor.
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  Data: <searchLink fieldCode="DE" term="%22Malaria%22">Malaria</searchLink><br /><searchLink fieldCode="DE" term="%22Endothelial+cells%22">Endothelial cells</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+C%22">Protein C</searchLink><br /><searchLink fieldCode="DE" term="%22Plasmodium+falciparum%22">Plasmodium falciparum</searchLink><br /><searchLink fieldCode="DE" term="%22Erythrocytes%22">Erythrocytes</searchLink><br /><searchLink fieldCode="DE" term="%22Juvenile+diseases%22">Juvenile diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Membrane+proteins%22">Membrane proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink>
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  Data: Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year. Sequestration is mediated by specific interactions between members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins was unknown. Here we identify endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C, as the endothelial receptor for DC8 and DC13 PfEMP1. We show that EPCR binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDRα1) of DC8 and group A PfEMP1 subfamilies, and that CIDRα1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways, and has implications for understanding malaria pathology and the development of new malaria interventions. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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