Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitroand targets cell junctions

Inflammation is a basic pathological mechanism that underlies many diseases . An important component of the inflammatory response is the passage of pla sma components and leukocytes from the blood vessel into the tissues. The e ndothelial monolayer lining blood vessels reacts to stimuli such as thrombi n or vascular endothelial growth factor by changes in cell-cell junctions, an increase in permeability, and the leakage of plasma components into tiss ues. Other stimuli, such as tumor necrosis factor-alpha (TNF-alpha), are re sponsible for stimulating the transmigration of leukocytes. Here we show th at angiopoietin-1, a cytokine essential in fetal angiogenesis, not only sup ports the localization of proteins such as platelet endothelial cell adhesi on molecule-1 (PECAM-1) into junctions between endothelial cells and decrea ses the phosphorylation of PECAM-1 and vascular endothelial cadherin, but i t also strengthens these junctions, as evidenced by a decrease in basal per meability and inhibition of permeability responses to thrombin and vascular endothelial growth factor. Furthermore, angiopoietin-1 inhibits TNF-alpha- stimulated leukocyte transmigration. Angiopoietin-1 may thus have a major r ole in maintaining the integrity of endothelial monolayers.