The lipid moiety of haemozoin (Malaria Pigment) and P. falciparum parasitised red blood cells bind synthetic and native endothelin-1.
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.
Basilico
Nicoletta
N
Dipartimento di Sanità Pubblica-Microbiologia-Virologia, Università degli Studi di Milano, via Pascal 36, 20133 Milan, Italy. nicoletta.basilico@unimi.it
Parapini
Silvia
S
Sisto
Francesca
F
Omodeo-Salè
Fausta
F
Coghi
Paolo
P
Ravagnani
Fernando
F
Olliaro
Piero
P
Taramelli
Donatella
D
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
D019332:Endothelin-1; D006420:Hemeproteins; D008055:Lipids; C020753:hemozoin