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Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum.

Publication ,  Journal Article
McMorran, BJ; Wieczorski, L; Drysdale, KE; Chan, J-A; Huang, HM; Smith, C; Mitiku, C; Beeson, JG; Burgio, G; Foote, SJ
Published in: Science
December 7, 2012

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 7, 2012

Volume

338

Issue

6112

Start / End Page

1348 / 1351

Location

United States

Related Subject Headings

  • Recombinant Proteins
  • Receptors, Cell Surface
  • Platelet Factor 4
  • Plasmodium falciparum
  • Malaria, Falciparum
  • Humans
  • General Science & Technology
  • Erythrocytes
  • Duffy Blood-Group System
  • Cells, Cultured
 

Citation

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McMorran, B. J., Wieczorski, L., Drysdale, K. E., Chan, J.-A., Huang, H. M., Smith, C., … Foote, S. J. (2012). Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum. Science, 338(6112), 1348–1351. https://doi.org/10.1126/science.1228892
McMorran, Brendan J., Laura Wieczorski, Karen E. Drysdale, Jo-Anne Chan, Hong Ming Huang, Clare Smith, Chalachew Mitiku, James G. Beeson, Gaetan Burgio, and Simon J. Foote. “Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum.Science 338, no. 6112 (December 7, 2012): 1348–51. https://doi.org/10.1126/science.1228892.
McMorran BJ, Wieczorski L, Drysdale KE, Chan J-A, Huang HM, Smith C, et al. Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum. Science. 2012 Dec 7;338(6112):1348–51.
McMorran, Brendan J., et al. “Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum.Science, vol. 338, no. 6112, Dec. 2012, pp. 1348–51. Pubmed, doi:10.1126/science.1228892.
McMorran BJ, Wieczorski L, Drysdale KE, Chan J-A, Huang HM, Smith C, Mitiku C, Beeson JG, Burgio G, Foote SJ. Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum. Science. 2012 Dec 7;338(6112):1348–1351.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 7, 2012

Volume

338

Issue

6112

Start / End Page

1348 / 1351

Location

United States

Related Subject Headings

  • Recombinant Proteins
  • Receptors, Cell Surface
  • Platelet Factor 4
  • Plasmodium falciparum
  • Malaria, Falciparum
  • Humans
  • General Science & Technology
  • Erythrocytes
  • Duffy Blood-Group System
  • Cells, Cultured