Publication Date:
2012-12-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMorran, Brendan J -- Wieczorski, Laura -- Drysdale, Karen E -- Chan, Jo-Anne -- Huang, Hong Ming -- Smith, Clare -- Mitiku, Chalachew -- Beeson, James G -- Burgio, Gaetan -- Foote, Simon J -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Dec 7;338(6112):1348-51. doi: 10.1126/science.1228892.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia. brendan.mcmorran@mq.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23224555" target="_blank"〉PubMed〈/a〉
Keywords:
Blood Platelets/*immunology
;
Cells, Cultured
;
Duffy Blood-Group System/genetics/*immunology
;
Erythrocytes/*parasitology
;
Humans
;
*Malaria, Falciparum/blood/immunology/parasitology
;
Plasmodium falciparum/drug effects/growth & development/*immunology
;
Platelet Factor 4/genetics/*immunology/pharmacology
;
Receptors, Cell Surface/genetics/*immunology
;
Recombinant Proteins/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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