title: Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum.
abstract: Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PF4 is released by platelets on contact with parasitized red cells, and the protein directly kills intraerythrocytic parasites. This function for PF4 is critically dependent on Fy, which binds PF4. Genetic disruption of Fy expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4. The protective function afforded by platelets during a malarial infection may therefore be compromised in Duffy-negative individuals, who do not express Fy.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia. brendan.mcmorran@mq.edu.au
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: McMorran
authors.forename: Laura
authors.initials: L
authors.lastname: Wieczorski
authors.forename: Karen E
authors.initials: KE
authors.lastname: Drysdale
authors.forename: Jo-Anne
authors.initials: JA
authors.lastname: Chan
authors.forename: Hong Ming
authors.initials: HM
authors.lastname: Huang
authors.forename: Clare
authors.initials: C
authors.lastname: Smith
authors.forename: Chalachew
authors.initials: C
authors.lastname: Mitiku
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.forename: Gaetan
authors.initials: G
authors.lastname: Burgio
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foote
mesh_terms: D001792:Blood Platelets / Q000276:immunology*; D002478:Cells, Cultured; D004375:Duffy Blood-Group System / Q000235:genetics / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D010978:Platelet Factor 4 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D010978:Platelet Factor 4