Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage

Fiorentina Roviezzo, Stelios Tsigkos, Anastasia Kotanidou, Mariarosaria Bucci, Vincenzo Brancaleone, Giuseppe Cirino, Andreas Papapetropoulos

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)738-744
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume314
Issue number2
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

Angiopoietin-2
Blood Vessels
Inflammation
Edema
Leukocytes
Angiopoietins
Zymosan
Dinoprostone
Endothelium
Cell Movement
Anti-Inflammatory Agents
Air
Ligands
Injections

ASJC Scopus subject areas

  • Pharmacology

Cite this

Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. / Roviezzo, Fiorentina; Tsigkos, Stelios; Kotanidou, Anastasia; Bucci, Mariarosaria; Brancaleone, Vincenzo; Cirino, Giuseppe; Papapetropoulos, Andreas.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 314, No. 2, 01.08.2005, p. 738-744.

Research output: Contribution to journalArticle

Roviezzo, Fiorentina ; Tsigkos, Stelios ; Kotanidou, Anastasia ; Bucci, Mariarosaria ; Brancaleone, Vincenzo ; Cirino, Giuseppe ; Papapetropoulos, Andreas. / Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. In: Journal of Pharmacology and Experimental Therapeutics. 2005 ; Vol. 314, No. 2. pp. 738-744.
@article{5e1406c9ed774e5b97c004c4a731e39b,
title = "Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage",
abstract = "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.",
author = "Fiorentina Roviezzo and Stelios Tsigkos and Anastasia Kotanidou and Mariarosaria Bucci and Vincenzo Brancaleone and Giuseppe Cirino and Andreas Papapetropoulos",
year = "2005",
month = "8",
day = "1",
doi = "10.1124/jpet.105.086553",
language = "English (US)",
volume = "314",
pages = "738--744",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage

AU - Roviezzo, Fiorentina

AU - Tsigkos, Stelios

AU - Kotanidou, Anastasia

AU - Bucci, Mariarosaria

AU - Brancaleone, Vincenzo

AU - Cirino, Giuseppe

AU - Papapetropoulos, Andreas

PY - 2005/8/1

Y1 - 2005/8/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=22944432543&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22944432543&partnerID=8YFLogxK

U2 - 10.1124/jpet.105.086553

DO - 10.1124/jpet.105.086553

M3 - Article

C2 - 15870388

AN - SCOPUS:22944432543

VL - 314

SP - 738

EP - 744

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -