Platelet factor 4 mediates inflammation in experimental cerebral malaria

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...

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Bibliographic Details
Published in:Cell host & microbe 2008-08, Vol.4 (2), p.179-187
Main Authors: Srivastava, Kalyan, Cockburn, Ian A, Swaim, AnneMarie, Thompson, Laura E, Tripathi, Abhai, Fletcher, Craig A, Shirk, Erin M, Sun, Henry, Kowalska, M Anna, Fox-Talbot, Karen, Sullivan, David, Zavala, Fidel, Morrell, Craig N
Format: Article
Language:English
Subjects:
Animals
Brain - immunology
Brain - parasitology
Erythrocytes - immunology
Erythrocytes - parasitology
Host-Pathogen Interactions
Humans
Malaria, Cerebral - immunology
Malaria, Cerebral - parasitology
Mice
Mice, Inbred C57BL
Mice, Knockout
Plasmodium falciparum
Plasmodium falciparum - immunology
Plasmodium falciparum - physiology
Platelet Activation
Platelet Factor 4 - genetics
Platelet Factor 4 - immunology
Receptors, CXCR3 - genetics
Receptors, CXCR3 - metabolism
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Summary: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.
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2008.07.003