Exp Mol Med.
2007 Dec;39(6):733-745.
Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1
- Affiliations
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- 1Department of Internal Medicine, Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju 561-180, Korea. leeyc@chonbuk.ac.kr
- 2Department of Internal Medicine, Chungnam National University Medical School, Daejeon 301-747, Korea.
- 3Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
- 4Department of Pathology, Chonbuk National University Medical School, Jeonju 561-180, Korea.
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.
MeSH Terms
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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
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