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, Kyung-Hoon Min, 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
Publication statusPublished - 2007 Dec 31
Externally publishedYes

Fingerprint

Respiratory Hypersensitivity
Angiopoietin-1
Inflammation
Capillary Permeability
Blood Vessels
Chemokine CCL5
Th2 Cells
Plasmas
Interleukin-13
Vascular Cell Adhesion Molecule-1
Interleukin-5
Intercellular Adhesion Molecule-1
Endothelial cells
Chemokines
Epidermal Growth Factor
Interleukin-4
Intravenous Administration
Protein-Tyrosine Kinases
Allergens
Lung Diseases

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Kyung, S. L., Ka, Y. L., So, R. K., Hee, S. P., Seoung, J. P., Min, K-H., ... 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.

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1. / Kyung, Sun Lee; Ka, Young Lee; So, Ri Kim; Hee, Sun Park; Seoung, Ju Park; Min, Kyung-Hoon; Cho, Chung Hyun; Gou, Young Koh; Ho, Sung Park; Yong, Chul Lee.

In: Experimental and Molecular Medicine, Vol. 39, No. 6, 31.12.2007, p. 733-745.

Research output: Contribution to journalArticle

Kyung, SL, Ka, YL, So, RK, Hee, SP, Seoung, JP, Min, K-H, Cho, CH, Gou, YK, Ho, SP & Yong, CL 2007, 'Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1', Experimental and Molecular Medicine, vol. 39, no. 6, pp. 733-745.
Kyung, Sun Lee ; Ka, Young Lee ; So, Ri Kim ; Hee, Sun Park ; Seoung, Ju Park ; Min, Kyung-Hoon ; Cho, Chung Hyun ; Gou, Young Koh ; Ho, Sung Park ; Yong, Chul Lee. / Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1. In: Experimental and Molecular Medicine. 2007 ; Vol. 39, No. 6. pp. 733-745.
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