Journal article
Platelet factor 4 and duffy antigen required for platelet killing of Plasmodium falciparum
BJ McMorran, L Wieczorski, KE Drysdale, JA Chan, HM Huang, C Smith, C Mitiku, JG Beeson, G Burgio, SJ Foote
Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2012
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 h..
View full abstractGrants
Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council
Funding Acknowledgements
We thank the Australian Red Cross Blood Services in Hobart and Brisbane for providing red blood cells and antibodies, the platelet donors, and C. Flowers and R. McWhirter for phlebotomy. We also acknowledge funding support from the National Health and Medical Research Council of Australia (grants 605524 and 490037), the Australian Cancer Research Foundation, the National Collaborative Research Infrastructure Strategy of Australia, The Bill and Melinda Gates Foundation Grand Challenges Explorations, The Howard Hughes Medical Institute, Australian Research Council (grant DP120100061 and Future Fellowship to J.G.B.), and the Victorian State Government Operational Infrastructure Support Scheme. Ethics approval for the platelet donations was received from the Human Research Ethics Committee (Tasmania) Network (H0009004). Data are deposited in the Dryad Repository: http://dx.doi.org/10.5061/dryad.8sb5h