New insights into the regulation of vascular permeability

The endothelium size selectively allows transport of fluids, ions, macromolecules, and leukocytes across the vessel wall paracellularly by dynamically opening intercellular junctions or transcellularly through caveolae. However, persistent opening of intercellular junctions leads to the formation of protein-rich edema in the interstitial tissue, a hallmark of tissue inflammation that, if left untreated, causes fatal diseases like acute respiratory distress syndrome (ARDS). The requirements for continuous transendothelial protein flux while limiting leukocyte flux into tissue imply that signaling processes exist in the endothelium that dynamically controls protein flux and leukocyte migration between the vascular and extravascular spaces. In this chapter, we discuss the signaling mechanisms elicited by several well-known inflammatory mediators that increase endothelial permeability. Specifically, we have concentrated in reviewing the new concepts dealing with the restoration of normal endothelial permeability by sphingosine kinase 1 following inflammatory stimulus.