Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production

Lara Pizurki, Zongmin Zhou, Konstantinos Glynos, Charis Roussos, Andreas Papapetropoulos

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

1. Angiopoietin-1 (Ang1) is an angiogenic growth factor that binds to the Tie2 receptor on vascular endothelium, promoting blood vessel maturation and integrity. In the present study, we have investigated whether Ang1 also possesses anti-inflammatory properties by determining its effects on endothelial barrier function, neutrophil (PMN) adherence to endothelial cells (EC) and production of the PMN chemotactic factor interleukin-8 (IL-8). 2. Pretreatment of endothelial monolayers with Ang1 attenuated the permeability increase induced by thrombin in both lung microvascular cells and a human endothelial cell line. Similarly, Ang1 prevented the permeability-inducing effects of platelet-activating factor, bradykinin and histamine. 3. Pretreatment of EC with Ang1 also reduced the adherence of PMN to EC stimulated by thrombin. In contrast to its ability to counteract the increase in monolayer permeability brought about by various inflammatory agents, Ang1 did not affect the ability of histamine, PAF, or tumor necrosis factor-α to stimulate PMN adherence to EC. 4. In addition to its ability to inhibit PMN adherence, Ang1 diminished IL-8 production from EC challenged with thrombin in a concentration-dependent manner. 5. When EC were preincubated with the specific Rho kinase (ROCK) inhibitor Y-27632, we observed a reduction in PMN adherence in response to thrombin, as well as a decrease in thrombin-stimulated IL-8 production. Coincubation of monolayers with Y-27632 and Ang1 did not further attenuate the above-mentioned responses. However, Ang-1 failed to inhibit the activation of RhoA in response to thrombin, suggesting that inhibition of EC adhesiveness for PMN and IL-8 production by Ang1 does not result from reduced ROCK activation. 6. We conclude that Ang1 can counteract several aspects of the inflammatory response, including endothelial permeability, PMN adherence to EC as well as inhibition of IL-8 production by EC.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalBritish Journal of Pharmacology
Volume139
Issue number2
DOIs
StatePublished - May 1 2003
Externally publishedYes

Fingerprint

Angiopoietin-1
Interleukin-8
Permeability
Neutrophils
Endothelial Cells
Thrombin
Histamine
TIE-2 Receptor
Adhesiveness
rho-Associated Kinases
Angiogenesis Inducing Agents
Platelet Activating Factor
Chemotactic Factors
Vascular Endothelium
Bradykinin
Blood Vessels
Intercellular Signaling Peptides and Proteins
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha

Keywords

  • Angiogenesis
  • Angiopoietin-1
  • Endothelium
  • IL-8
  • Inflammation
  • Neutrophils
  • Permeability
  • ROCK
  • Thrombin
  • Tie2

ASJC Scopus subject areas

  • Pharmacology

Cite this

Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. / Pizurki, Lara; Zhou, Zongmin; Glynos, Konstantinos; Roussos, Charis; Papapetropoulos, Andreas.

In: British Journal of Pharmacology, Vol. 139, No. 2, 01.05.2003, p. 329-336.

Research output: Contribution to journalArticle

Pizurki, Lara ; Zhou, Zongmin ; Glynos, Konstantinos ; Roussos, Charis ; Papapetropoulos, Andreas. / Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. In: British Journal of Pharmacology. 2003 ; Vol. 139, No. 2. pp. 329-336.
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