Platelet Factor 4 Mediates Inflammation in Experimental Cerebral Malaria

Kalyan Srivastava, Ian A. Cockburn, Anne Marie Swaim, Laura E. Thompson, Abhai Tripathi, Craig A. Fletcher, Erin M. Shirk, Henry Sun, M. Anna Kowalska, Karen Fox-Talbot, David Sullivan, Fidel Zavala, Craig N. Morrell

Research output: Contribution to journalArticlepeer-review


Cerebral malaria (CM) is a major complication of Plasmodium falciparum infection in children. The pathogenesis of CM involves vascular inflammation, immune stimulation, and obstruction of cerebral capillaries. Platelets have a prominent role in both immune responses and vascular obstruction. We now demonstrate that the platelet-derived chemokine, platelet factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria (ECM). Plasmodium-infected red blood cells (RBCs) activated platelets independently of vascular effects, resulting in increased plasma PF4. PF4 or chemokine receptor CXCR3 null mice had less severe ECM, including decreased T cell recruitment to the brain, and platelet depletion or aspirin treatment reduced the development of ECM. We conclude that Plasmodium-infected RBCs can directly activate platelets, and platelet-derived PF4 then contributes to immune activation and T cell trafficking as part of the pathogenesis of ECM.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalCell Host and Microbe
Issue number2
StatePublished - Aug 14 2008



ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology


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