P2X1: a unique platelet receptor with a key role in thromboinflammation

Thromboinflammation involves complex interactions between actors of inflammation and immunity and components of the hemostatic system, which are elicited upon infection or tissue injury. In this context, the interplay between platelets and innate immune cells has been intensively investigated. The ATP-gated P2X1 ion channel, expressed on both platelets and neutrophils is of particular interest. On platelets, this ion channel contributes to platelet activation and thrombosis, especially under high shear stress conditions of small arteries, whereas on neutrophils, it is involved in chemotaxis and in mitigating the activation of circulating cells. In vitro studies indicate that it may also be implicated in platelet-dependent immune responses during bacterial infection. More recently, in a mouse model of intestinal epithelial barrier disruption causing systemic inflammation, it has been reported that neutrophil P2X1 ion channel could play a protective role against exaggerated inflammation-associated thrombosis. This review will focus on this unique role of the ATP-gated P2X1 ion channel in thromboinflammation, highlighting possible implications and pointing to the need for further investigation of the role of P2X1 ion channels in the interplay between platelets and neutrophils during thrombus formation under various sterile or infectious inflammatory settings and in distinct vascular beds.