title: Purinergic control of inflammation and thrombosis: Role of P2X1 receptors.
abstract: Inflammation shifts the hemostatic mechanisms in favor of thrombosis. Upon tissue damage or infection, a sudden increase of extracellular ATP occurs, that might contribute to the crosstalk between inflammation and thrombosis. On platelets, P2X1 receptors act to amplify platelet activation and aggregation induced by other platelet agonists. These receptors critically contribute to thrombus stability in small arteries. Besides platelets, studies by our group indicate that these receptors are expressed by neutrophils. They promote neutrophil chemotaxis, both in vitro and in vivo. In a laser-induced injury mouse model of thrombosis, it appears that neutrophils are required to initiate thrombus formation and coagulation activation on inflamed arteriolar endothelia. In this model, by using P2X1-/ - mice, we recently showed that P2X1 receptors, expressed on platelets and neutrophils, play a key role in thrombus growth and fibrin generation. Intriguingly, in a model of endotoxemia, P2X1-/ - mice exhibited aggravated oxidative tissue damage, along with exacerbated thrombocytopenia and increased activation of coagulation, which translated into higher susceptibility to septic shock. Thus, besides its ability to recruit neutrophils and platelets on inflamed endothelia, the P2X1 receptor also contributes to limit the activation of circulating neutrophils under systemic inflammatory conditions. Taken together, these data suggest that P2X1 receptors are involved in the interplay between platelets, neutrophils and thrombosis. We propose that activation of these receptors by ATP on neutrophils and platelets represents a new mechanism that regulates thrombo-inflammation.
authors.affiliation: Laboratory of Thrombosis and Hemostasis, GIGA -Cardiovascular Sciences, University of Liège, Liège, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Oury
authors.affiliation: Laboratory of Thrombosis and Hemostasis, GIGA -Cardiovascular Sciences, University of Liège, Liège, Belgium.
authors.forename: Christelle
authors.initials: C
authors.lastname: Lecut
authors.affiliation: Laboratory of Thrombosis and Hemostasis, GIGA -Cardiovascular Sciences, University of Liège, Liège, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hego
authors.affiliation: Laboratory of Thrombosis and Hemostasis, GIGA -Cardiovascular Sciences, University of Liège, Liège, Belgium.
authors.forename: Odile
authors.initials: O
authors.lastname: Wéra
authors.affiliation: Laboratory of Thrombosis and Hemostasis, GIGA -Cardiovascular Sciences, University of Liège, Liège, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Delierneux
keywords: Inflammation; P2X receptor; Thrombosis