TGF-beta(1) released from activated platelets can induce TNF-stimulated human brain endothelium apoptosis: A new mechanism for microvascular lesion during cerebral malaria


Wassmer, SC; de Souza, JB; Frère, C; Candal, FJ; Juhan-Vague, I; Grau, GE; (2006) TGF-beta(1) released from activated platelets can induce TNF-stimulated human brain endothelium apoptosis: A new mechanism for microvascular lesion during cerebral malaria. Journal of immunology (Baltimore, Md, 176 (2). pp. 1180-4. ISSN 0022-1767

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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.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 16394007
Web of Science ID: 234553800062
URI: http://researchonline.lshtm.ac.uk/id/eprint/12161

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