Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions.
Inflammation is a basic pathological mechanism that underlies many diseases. An important component of the inflammatory response is the passage of plasma components and leukocytes from the blood vessel into the tissues. The endothelial monolayer lining blood vessels reacts to stimuli such as thrombin or vascular endothelial growth factor by changes in cell-cell junctions, an increase in permeability, and the leakage of plasma components into tissues. Other stimuli, such as tumor necrosis factor-alpha (TNF-alpha), are responsible for stimulating the transmigration of leukocytes. Here we show that angiopoietin-1, a cytokine essential in fetal angiogenesis, not only supports the localization of proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1) into junctions between endothelial cells and decreases the phosphorylation of PECAM-1 and vascular endothelial cadherin, but it also strengthens these junctions, as evidenced by a decrease in basal permeability 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 role in maintaining the integrity of endothelial monolayers.
Gamble
J R
JR
Vascular Biology Laboratory, Division of Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science and the University of Adelaide, South Australia. jennifer.gamble@imvs.sa.gov.au
Drew
J
J
Trezise
L
L
Underwood
A
A
Parsons
M
M
Kasminkas
L
L
Rudge
J
J
Yancopoulos
G
G
Vadas
M A
MA
D042683:Angiopoietin-1; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D010539:Permeability; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
D042683:Angiopoietin-1; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015820:Cadherins; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1