Le CD154 plaquettaire : Une nouvelle interface dans l’hémostase et la réaction inflammatoire

Platelet-associated CD154: a new interface in haemostasis and in the inflammatory reaction

¹ GREF Inserm E362, IFR 66, Université de Bordeaux 2 et Département de Néphrologie, Hôpital Pellegrin, place Amélie Raba Léon, 33076 Bordeaux Cedex, France
² GREF Inserm E362 et IFR 66, Université de Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux Cedex France
³ IFR 4 et Laboratoire d’Hématologie, Hôpital Cardiologique, avenue de Magellan, 33604 Pessac, France
⁴ Inserm E0217, Université de Bordeaux 2-Victor Segalen, 146, rue Léo Saignat, 33076 Bordeaux Cedex France
⁵ CIRID CNRS UMR 5164, Université de Bordeaux 2-Victor Segalen, 146, rue Léo Saignat, 33076 ordeaux Cedex France
⁶ Service de édecine Interne, Hôpital du Haut-Lévêque, avenue du Haut- évêque, 33604 Pessac, France

^* yahsou.delmas@chu-bordeaux.fr

Résumé

Il a récemment été montré que les plaquettes sanguines exprimaient le CD154 (ligand du CD40), qu’elles extériorisent à leur surface lors de leur activation. Cette découverte a eu des consequences importantes sur la compréhension de la biologie de la plaquette. D’une part, le CD154intervient dans la stabilisation du thrombus plaquettaire. D’autre part, l’interaction des plaquettes avec les cellules exprimant le récepteur CD40 a mis en évidence de nouvelles interfaces liant les plaquettes à la réaction inflammatoire, la coagulation et le remodelage de la matrice extracellulaire. Cela est tout particulièrement vrai pour les interactions plaquettes/vaisseaux et le CD154 plaquettaire joue un rôle clé dans la maladie athéromateuse. Enfin, l’expression du CD154 confère aux plaquettes une competence immunologique, leur faisant jouer un role potentiel dans la réponse immune ou dans les pathologies associées à une auto-immunisation antiplaquettaire comme le purpura thrombopénique idiopathique.

Abstract

Blood platelets play a crucial part in the blood clotting process by forming the platelet plug. Recent evidence indicates that they are likely to play a key role in the inflammatory reaction via CD154/CD40 interactions. CD40 was known to be widely expressed, for instance on cells of the vasculature including endothelial cells, smooth muscle cells and macrophages. It was also known that the triggering of CD40 on these cells led to the acquisition of an activated pro-inflammatory and pro-coagulant phenotype. It was subsequently shown that platelets express CD154 which is cryptic in unstimulated platelets but is expressed at the platelet surface upon platelet activation. When expressed at the platelet surface and exposed to CD40-expressing vascular cells, the platelet-associated CD154 triggers a variety of pro-inflammatory and pro-coagulant responses including induction of adhesion receptors, release of cytokines and chemokines, induction of tissue factor and of metalloproteinases. Plateletassociated CD154 is also involved in platelet/platelet interactions during platelet aggregation. Furthermore, in vivo models have emphasized the critical role of the platelet-associated CD154 in the progression of atherosclerotic disease and in the stabilization of arterial thrombi. Recent data show that CD40-bearing cells involved in fibrosis such as hepatic stellate cells and glomerular mesangial cells also respond to plateletassociated CD154, thus suggesting a new mechanism by which platelets may be instrumental in the inflammatory diseases of the liver or the kidney. Finally, platelet-associated CD154 has been shown to have immune competence both in vitro and in vivo, observations that open new fields of research on the potential implications of platelets in the immune response and auto-immune diseases.