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Science 338 (6112): 1348-1351

Copyright © 2012 by the American Association for the Advancement of Science

Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum

Brendan J. McMorran,1,2,* Laura Wieczorski,2 Karen E. Drysdale,2 Jo-Anne Chan,3 Hong Ming Huang,1 Clare Smith,2 Chalachew Mitiku,2 James G. Beeson,3 Gaetan Burgio,1,2 Simon J. Foote1,2

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.

1 Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia.
2 Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000, Australia.
3 Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia.

* To whom correspondence should be addressed. E-mail: brendan.mcmorran{at}mq.edu.au


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors.
F. Bachelerie, A. Ben-Baruch, A. M. Burkhardt, C. Combadiere, J. M. Farber, G. J. Graham, R. Horuk, A. H. Sparre-Ulrich, M. Locati, A. D. Luster, et al. (2014)
Pharmacol. Rev. 66, 1-79
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