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KMID : 0620920070390060733
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Experimental & Molecular Medicine
2007 Volume.39 No. 6 p.733 ~ p.745
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Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1
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Lee Kyung-Sun
Lee Ka-Young
Kim So-Ri
Park Hee-Sun
Park Seoung-Ju
Min Kyung-Hoon
Cho Chung-Hyun
Koh Gou-Young
Park Ho-Sung
Lee Yong-Chul
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Abstract
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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.
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KEYWORD
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angiopoietin-1, asthma, capillary permeability, receptor, Tie-2
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