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

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 conséquences importantes sur la compréhension de la biologie de la plaquette. D’une part, le CD154 intervient 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 compétence immunologique, leur faisant jouer un rôle potentiel dans la réponse immune ou dans les pathologies associées à une auto-immunisation antiplaquettaire comme le purpura thrombopénique idiopathique.

Summary

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. Platelet-associated 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 platelet-associated 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.