Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1.
- Author:
Kyung Sun LEE
1
;
Ka Young LEE
;
So Ri KIM
;
Hee Sun PARK
;
Seoung Ju PARK
;
Kyung Hoon MIN
;
Chung Hyun CHO
;
Gou Young KOH
;
Ho Sung PARK
;
Yong Chul LEE
Author Information
1. Department of Internal Medicine, Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju 561-180, Korea. leeyc@chonbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
angiopoietin-1;
asthma;
capillary permeability;
receptor, Tie-2
- MeSH:
Allergens/immunology;
Angiopoietin-1/genetics/pharmacology/*therapeutic use;
Animals;
Asthma/*prevention & control;
Bronchial Hyperreactivity/physiopathology/prevention & control;
Chemokines/metabolism;
Inflammation/pathology/*prevention & control;
Mice;
Mice, Inbred C57BL;
Recombinant Fusion Proteins/*therapeutic use
- From:Experimental & Molecular Medicine
2007;39(6):733-745
- CountryRepublic of Korea
- Language:English
-
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.
