| Inflammatory pulmonary conditions found in disease states such as ischemia-reperfusion, sepsis and acute lung injury have the hallmark increased permeability of the microvessels resulting in profound pathophysiological edema.{09}Regulation of the barrier formed by the endothelial cells lining the blood vessels is responsible for the controlled flux of fluid and macromolecules from the vascular space to the surrounding tissues. It is the compromise of this regulated flux that is responsible for the edema. Endothelial barrier integrity depends on the balance of two opposing forces, basal tension generated by the actin cytoskeleton and tethering forces mediated by cell adhesion complexes. The adherens junction plays an important role in regulating the barrier function of blood vessels by the endothelial cells. VE-cadherin is a single pass transmembrane protein found in endothelial cell adherens junctions that has been shown to play an important role in regulating endothelial monolayer integrity. N-cadherin is also found in endothelial cells; however, the relationship between N-cadherin and VE-cadherin in regulating endothelial cell function is not completely understood. Interestingly, an inverse relationship was found between N-cadherin and VE-cadherin expression levels in endothelial cells from different tissues. Our studies have also shown that p120 plays an important role in maintaining VE-cadherin levels but not N-cadherin levels in endothelial cells, indicating that p120 interaction with these two cadherins may be a point of regulation of the respective cadherin complexes and their role in endothelial monolayer integrity. |
