title: Platelet factor 4 mediates inflammation in experimental cerebral malaria.
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.
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Srivastava
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cockburn
authors.forename: AnneMarie
authors.initials: A
authors.lastname: Swaim
authors.forename: Laura E
authors.initials: LE
authors.lastname: Thompson
authors.forename: Abhai
authors.initials: A
authors.lastname: Tripathi
authors.forename: Craig A
authors.initials: CA
authors.lastname: Fletcher
authors.forename: Erin M
authors.initials: EM
authors.lastname: Shirk
authors.forename: Henry
authors.initials: H
authors.lastname: Sun
authors.forename: M Anna
authors.initials: MA
authors.lastname: Kowalska
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: David
authors.initials: D
authors.lastname: Sullivan
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
authors.forename: Craig N
authors.initials: CN
authors.lastname: Morrell
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000469:parasitology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D054884:Host-Pathogen Interactions; D006801:Humans; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology*; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000235:genetics / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism
chemical_list: C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D010978:Platelet Factor 4