TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction.

Détails

ID Serval
serval:BIB_818673C2AF27
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction.
Périodique
European Cytokine Network
Auteur(s)
Grau G.E., Tacchini-Cottier F., Vesin C., Milon G., Lou J.N., Piguet P.F., Juillard P.
ISSN
1148-5493 (Print)
ISSN-L
1148-5493
Statut éditorial
Publié
Date de publication
1993
Volume
4
Numéro
6
Pages
415-419
Langue
anglais
Résumé
Pathogenic mechanisms of brain microvascular injury were studied in an experimental model of cerebral malaria (CM). The lesion, leading to perivascular microhemorrhages, is due to cytokine overproduction, and is associated with the sequestration of macrophages and parasitized erythrocytes in cerebral venules. In this in vivo model, we demonstrate that platelets are critical effectors of the neurovascular injury. First, electron microscopy indicated that during CM platelets adhere to and probably damage brain endothelial cells. Second, radiolabelled platelet distribution studies indicated that platelets sequestered in the brain and lung vasculature during CM. Non-cerebral malaria was not associated with cerebral sequestration of platelets. Third, in vivo treatment with a mAb to LFA-1 (which is expressed on platelets) selectively abrogated the cerebral sequestration of platelets, and this correlated with prevention of CM. Fourth, malaria-infected animals rendered thrombocytopenic were significantly protected against CM, further indicating that platelets are central to the pathogenesis of CM. Thus, a CD11a-dependent interaction between platelets and endothelial cells appears pivotal to microvascular damage. These data suggest a novel mechanism of action for anti-LFA-1 mAb in vivo and illustrate an unexpected role of platelets, in addition to monocytes, in vascular pathology.
Mots-clé
Animals, Blood Platelets/physiology, Blood Platelets/ultrastructure, Brain/blood supply, Brain/pathology, Capillaries/pathology, Cell Adhesion Molecules/metabolism, Disease Models, Animal, Intercellular Adhesion Molecule-1, Lymphocyte Function-Associated Antigen-1/metabolism, Malaria, Cerebral/pathology, Mice, Mice, Inbred CBA, Microscopy, Electron, Plasmodium berghei, Tumor Necrosis Factor-alpha/physiology
Pubmed
Web of science
Création de la notice
24/01/2008 15:09
Dernière modification de la notice
20/08/2019 14:41
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