Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Sun Lee Kyung, Young Lee Ka, Ri Kim So, Sun Park Hee, Ju Park Seoung, Hoon Min Kyung, Chung Hyun Cho, Young Koh Gou, Sung Park Ho, Chul Lee Yong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage. Recently, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 receptor in lung endothelial cells. We have used a mouse model for allergic airway disease to determine effects of COMP-Ang1 on allergen-induced bronchial inflammation and airway hyper-responsiveness. These mice develop the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased levels of Th2 cell cytokines (IL-4, IL-5, and IL-13), adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), and chemokines (eotaxin and RANTES), and increased vascular permeability. Intravenous administration of COMP-Ang1 reduced bronchial inflammation and airway hyper-responsiveness. In addition, the increased plasma extravasation in allergic airway disease was significantly reduced by the administration of COMP-Ang1. These results suggest that COMP-Ang1 attenuates airway inflammation and hyper-responsiveness, prevents vascular leakage, and may be used as a therapeutic agent in allergic airway disease.

Original languageEnglish
Pages (from-to)733-745
Number of pages13
JournalExperimental and Molecular Medicine
Volume39
Issue number6
DOIs
Publication statusPublished - 2007 Dec 31

Keywords

  • Angiopoietin-1
  • Asthma
  • Capillary permeability
  • Receptor, tie-2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1'. Together they form a unique fingerprint.

  • Cite this

    Kyung, S. L., Ka, Y. L., So, R. K., Hee, S. P., Seoung, J. P., Kyung, H. M., Cho, C. H., Gou, Y. K., Ho, S. P., & Yong, C. L. (2007). Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1. Experimental and Molecular Medicine, 39(6), 733-745. https://doi.org/10.1038/emm.2007.80