Integrins and coagulation: a role for ROS/redox signaling?
Integrin regulation and signaling play a central role in the hemostasis process, particularly at the level of endothelial cells by regulating the contractility and barrier function of these cells and in platelets by controlling adhesion and aggregation at the site of cell injury. Reactive oxygen species (ROS) have emerged as an important mediator both transducing the signals associated with integrin activation and modulating integrin function. Ligation of integrins in endothelial cells and platelets induces activation of the Ras/mitogen-activated protein kinase, nuclear factor-kappaB, and phosphatidylinositol 3-kinase and Rho-GTPases pathways. Following vessel-wall injury and associated with activation and recruitment of platelets, there is a production of ROS concomitant with the stimulation of the blood coagulation. Moreover, ROS are capable of inducing conformational changes in integrins to change their binding affinity and function. This review will explore how ROS have emerged as an important modulator of integrins in coagulation through both outside-in (integrins stimulating ROS production to effect intracellular events) and inside-out signaling (intracellular ROS altering integrin function).