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Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum
journal contribution
posted on 2023-05-17, 15:24 authored by McMorran, BJ, Wieczorski, L, Drysdale, KE, Chan, J-A, Huang, HM, Smith, C, Mitiku, C, Beeson, JG, Burgio, G, Simon James FooteSimon James FootePlatelets 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.
Funding
National Health & Medical Research Council
History
Publication title
ScienceVolume
338Issue
6112Pagination
1348-1351ISSN
0036-8075Department/School
Menzies Institute for Medical ResearchPublisher
Amer Assoc Advancement SciencePlace of publication
1200 New York Ave, Nw, Washington, USA, Dc, 20005Rights statement
Copyright The AuthorsRepository Status
- Restricted