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

摘要: Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event the pathogenesis severe childhood malaria, which responsible for about one million deaths every year. mediated by specific interactions between members P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on endothelial lining. Severe malaria associated with expression PfEMP1 subtypes containing domain cassettes (DCs) 8 13 (ref. 3), but receptor parasites expressing these proteins was unknown. Here we identify C (EPCR), mediates cytoprotective effects activated C, as DC8 DC13 PfEMP1. We show that EPCR binding through amino-terminal cysteine-rich interdomain region (CIDRα1) group A subfamilies, CIDRα1 interferes to EPCR. This adhesive property links cytoadhesion involved anticoagulation pathways, has implications understanding pathology development new interventions.