Τίτλος:
Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Angiopoietins (Angs) are endothelium-selective ligands that exert most of their actions through the Tie-2 receptor. It is widely accepted that Ang-1 promotes the structural integrity of blood vessels and exhibits anti-inflammatory properties. In contrast, the role of Ang-2 remains less clear because it has been shown to behave as a Tie-2 agonist or antagonist under different experimental conditions. To define the role of Ang-2 in acute inflammation, we studied the effects of recombinant Ang-2 administration in vivo. We show herein that Ang-2, but not Ang-1, induces edema formation in the mouse paw in a dose-dependent manner; the edema seems to be fast-peaking (maximum at 30 min) and resolves within 4 h. The effect of Ang-2 is blocked by the coadministration with a soluble form of the Tie-2 receptor or Ang-1. NO and prostaglandin E2 levels in mouse paw following the injection of Ang-2 remained unaltered, suggesting that the action of Ang-2 does not involve these mediators. In addition, Ang-2 exerted a weak stimulatory effect on leukocyte migration in the mouse paw. Similarly, Ang-2 injected into the mouse air pouch produced only a modest effect on cell extravasation that peaked at 30 min. However, when cell migration was elicited using zymosan, Ang-2 significantly inhibited leukocyte migration. We conclude that Ang-2 by itself stimulates the extravasation of cell-poor fluid, but in the presence of ongoing inflammation it reduces cellular infiltration in tissues. Copyright © 2005 by The American Society for Pharmacology and Experimental Therapeutics.
Συγγραφείς:
Roviezzo, F.
Tsigkos, S.
Kotanidou, A.
Bucci, M.
Brancaleone, V.
Cirino, G.
Papapetropoulos, A.
Περιοδικό:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Λέξεις-κλειδιά:
angiopoietin 1; angiopoietin 2; angiopoietin receptor; nitric oxide; prostaglandin E2; zymosan, animal cell; animal experiment; article; cell infiltration; dose response; edema; extravasation; inflammation; inhibition kinetics; leukocyte migration; male; mouse; nonhuman; priority journal; stimulation, Angiopoietin-1; Angiopoietin-2; Animals; Blood Vessels; Capillary Permeability; Cell Movement; Dinoprostone; Edema; Endothelium, Vascular; Enzyme Inhibitors; Exudates and Transudates; Inflammation; Leukocytes; Male; Mice; Nitric Oxide; Peroxidase; Receptor, TIE-2; Vascular Endothelial Growth Factor A; Zymosan
DOI:
10.1124/jpet.105.086553
