title: TGF-beta1 released from activated platelets can induce TNF-stimulated human brain endothelium apoptosis: a new mechanism for microvascular lesion during cerebral malaria.
abstract: Platelets have recently been shown to accumulate in brain microvessels of patients with cerebral malaria and to modulate the binding of Plasmodium falciparum-infected red cells to human brain endothelium in vitro. In the present study we used a platelet-endothelial cell coculture model to investigate the mechanisms by which platelets modify the function of human brain microvascular endothelial cells (HBEC). Platelets were found to have a proapoptotic effect on TNF-activated HBEC, and this was contact-dependent, as inhibiting platelet binding prevented endothelial cell killing. We also showed that the supernatants of thrombin-activated platelets killed TNF-stimulated HBEC and that TGF-beta1 was the main molecule involved in endothelial cell death, because its inhibition completely abrogated the activated-platelet supernatant effect. Our data illustrate another aspect of the duality of TGF-beta1 in malaria and may provide new insights into the pathogenesis of cerebral malaria.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche (UMR) 6020, Faculty of Medicine, Institut Fédératif de Recherches (IFR) 48, Université de la Méditerranée, Marseille, France.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Wassmer
authors.forename: J Brian
authors.initials: JB
authors.lastname: de Souza
authors.forename: Corinne
authors.initials: C
authors.lastname: Frère
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Candal
authors.forename: Irène
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
mesh_terms: D000818:Animals; D017209:Apoptosis; D001792:Blood Platelets / Q000276:immunology*; D001921:Brain / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D016779:Malaria, Cerebral / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008833:Microcirculation / Q000276:immunology / Q000473:pathology; D010963:Plasmodium falciparum / Q000472:pathogenicity; D015539:Platelet Activation; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha