title: The lipid moiety of haemozoin (Malaria Pigment) and P. falciparum parasitised red blood cells bind synthetic and native endothelin-1.
abstract: Endothelin1 (ET-1) is a 21-amino acid peptide produced by the vascular endothelium under hypoxia, that acts locally as regulator of vascular tone and inflammation. The role of ET-1 in Plasmodium falciparum malaria is unknown, although tissue hypoxia is frequent as a result of the cytoadherence of parasitized red blood cell (pRBC) to the microvasculature. Here, we show that both synthetic and endothelial-derived ET-1 are removed by parasitized RBC (D10 and W2 strains, chloroquine sensitive, and resistant, resp.) and native haemozoin (HZ, malaria pigment), but not by normal RBC, delipidized HZ, or synthetic beta-haematin (BH). The effect is dose dependent, selective for ET-1, but not for its precursor, big ET-1, and not due to the proteolysis of ET-1. The results indicate that ET-1 binds to the lipids moiety of HZ and membranes of infected RBCs. These findings may help understanding the consequences of parasite sequestration in severe malaria.
authors.affiliation: Dipartimento di Sanità Pubblica-Microbiologia-Virologia, Università degli Studi di Milano, via Pascal 36, 20133 Milan, Italy. nicoletta.basilico@unimi.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Basilico
authors.forename: Silvia
authors.initials: S
authors.lastname: Parapini
authors.forename: Francesca
authors.initials: F
authors.lastname: Sisto
authors.forename: Fausta
authors.initials: F
authors.lastname: Omodeo-Salè
authors.forename: Paolo
authors.initials: P
authors.lastname: Coghi
authors.forename: Fernando
authors.initials: F
authors.lastname: Ravagnani
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
mesh_terms: D002460:Cell Line; D042783:Endothelial Cells; D019332:Endothelin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D006420:Hemeproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008055:Lipids; D016778:Malaria, Falciparum / Q000097:blood* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D019332:Endothelin-1; D006420:Hemeproteins; D008055:Lipids; C020753:hemozoin