Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1
Experimental & Molecular Medicine
;
: 733-745, 2007.
Article
in English
| WPRIM
| ID: wpr-21105
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Asthma
/
Recombinant Fusion Proteins
/
Allergens
/
Bronchial Hyperreactivity
/
Chemokines
/
Angiopoietin-1
/
Inflammation
/
Mice, Inbred C57BL
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2007
Type:
Article
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