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Infection and Immunity, January 2006, p. 645-653, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.645-653.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Platelets Potentiate Brain Endothelial Alterations Induced by Plasmodium falciparum

Samuel C. Wassmer,^1, Valéry Combes,¹ Francisco J. Candal,² Irène Juhan-Vague,³ and Georges E. Grau^1*

Laboratory of Immunopathology, Unité des Rickettsies CNRS UMR6020, IFR 48, Faculty of Medicine, Université de la Méditerranée, 27, Bd. Jean Moulin, F-13385 Marseille Cedex 05, France,¹ Centers for Disease Control and Prevention, National Center for Infectious Diseases, Atlanta, Georgia 30333,² Laboratory of Haematology and Haemostasis, Fibrinolysis and Vascular Pathology, INSERM UMR 626, IFR 125, Faculty of Medicine, Université de la Méditerranée, 27, Bd. Jean Moulin, F-13385 Marseille Cedex 05, France³

Received 1 December 2004/ Returned for modification 20 January 2005/ Accepted 20 October 2005

Brain lesions of cerebral malaria (CM) are characterized by a sequestration of Plasmodium falciparum-parasitized red blood cells (PRBC) and platelets within brain microvessels, as well as by blood-brain barrier (BBB) disruption. In the present study, we evaluated the possibility that PRBC and platelets induce functional alterations in brain endothelium. In a human brain endothelial cell line, named HBEC-5i, exhibiting most of the features demanded for a pathophysiological study of BBB, tumor necrosis factor (TNF) or lymphotoxin (LT-) reduced transendothelial electrical resistance (TEER), enhanced the permeability to 70-kDa dextran, and increased the release of microparticles, a recently described indicator of disease severity in CM patients. In vitro cocultures showed that platelets or PRBC can have a direct cytotoxic effect on activated, but not on resting, HBEC-5i cells. Platelet binding was required, as platelet supernatant had no effect. Furthermore, platelets potentiated the cytotoxicity of PRBC for TNF- or LT--activated HBEC-5i cells when they were added prior to these cells on the endothelial monolayers. This effect was not observed when platelets were added after PRBC. Both permeability and TEER were strongly affected, and the apoptosis rate of HBEC-5i cells was dramatically increased. These findings provide insights into the mechanisms by which platelets can be deleterious to the brain endothelium during CM.

Editor: J. F. Urban, Jr.

Present address: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, P.O. Box 30096, Chichiri, Blantyre 3, Malawi.

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