PT  - JOURNAL ARTICLE
AU  - Roviezzo, Fiorentina
AU  - Tsigkos, Stelios
AU  - Kotanidou, Anastasia
AU  - Bucci, Mariarosaria
AU  - Brancaleone, Vincenzo
AU  - Cirino, Giuseppe
AU  - Papapetropoulos, Andreas
TI  - Angiopoietin-2 Causes Inflammation in Vivo by Promoting Vascular Leakage
AID  - 10.1124/jpet.105.086553
DP  - 2005 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 738--744
VI  - 314
IP  - 2
4099  - http://jpet.aspetjournals.org/content/314/2/738.short
4100  - http://jpet.aspetjournals.org/content/314/2/738.full
SO  - J Pharmacol Exp Ther2005 Aug 01; 314
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics