Pulmonary vascular barrier regulation by thrombin and edg receptors

Lung vascular permeability is directly determined by the integrity of the endothelial cell (EC) monolayer, which involves dynamic regulation by the actomyosin cytoskeleton with subsequent effects on cell - cell and cell - matrix interactions. Although the list of biochemical and biophysical agonists that alter EC barrier regulation is extensive, in this chapter we consider two in particular - the barrier-disruptive serine protease thrombin and barrier-enhancing sphingosine-1-phosphate, an activator of the Edg receptor. Both agonists, via elaborate receptor-specific and tightly orchestrated signaling pathways, offer important insights into lung vascular barrier regulation with respect to the role of individual cellular components and signaling events that target the endothelial cytoskeleton. Additionally, we detail the combined effect of thrombin and cyclic stretch, mechanistically distinct agonists, to provide further insight into lung vascular regulation. Our understanding of EC barrier regulation and lung vascular permeability has advanced remarkably in only a short time and, with the use of newly available technologies, will undoubtedly continue to rapidly evolve.