Platelet factor 4 mediates inflammation in experimental cerebral malaria.

Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
Cell host & microbe (Impact Factor: 13.02). 09/2008; 4(2):179-87. DOI:10.1016/j.chom.2008.07.003
Source: PubMed

ABSTRACT 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.

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