© 2000 American Heart Association, Inc.
Molecular Medicine |
Angiopoietin-1 Is an Antipermeability and Anti-Inflammatory Agent In Vitro and Targets Cell Junctions
From the Vascular Biology Laboratory, Division of Immunology, Hanson Centre for Cancer Research (J.R.G., J.D., L.T., M.P., L.K., M.A.V.), Institute of Medical and Veterinary Science and the University of Adelaide, South Australia; CSIRO Molecular Science (A.U.), North Ryde, New South Wales, Australia; and Regeneron Pharmaceuticals, Inc (J.R., G.Y.), Tarrytown, NY.
Correspondence to J.R. Gamble, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science and the University of Adelaide, Frome Road, Adelaide, South Australia 5000. E-mail jennifer.gamble{at}imvs.sa.gov.au
Abstract—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-
(TNF-), 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-–stimulated leukocyte transmigration. Angiopoietin-1
may thus have a major role in maintaining the integrity of
endothelial monolayers.
Key Words: endothelium • inflammation • permeability • angiogenesis • cell junctions
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