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 language | English |
|---|---|
| Pages (from-to) | 733-745 |
| Number of pages | 13 |
| Journal | Experimental and Molecular Medicine |
| Volume | 39 |
| Issue number | 6 |
| Publication status | Published - 2007 Dec 31 |
| Externally published | Yes |
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Keywords
- Angiopoietin-1
- Asthma
- Capillary permeability
- Receptor, tie-2
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
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 journal › Article
}
TY - JOUR
T1 - Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1
AU - Kyung, Sun Lee
AU - Ka, Young Lee
AU - So, Ri Kim
AU - Hee, Sun Park
AU - Seoung, Ju Park
AU - Min, Kyung-Hoon
AU - Cho, Chung Hyun
AU - Gou, Young Koh
AU - Ho, Sung Park
AU - Yong, Chul Lee
PY - 2007/12/31
Y1 - 2007/12/31
N2 - 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.
AB - 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.
KW - Angiopoietin-1
KW - Asthma
KW - Capillary permeability
KW - Receptor, tie-2
UR - http://www.scopus.com/inward/record.url?scp=38049141251&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38049141251&partnerID=8YFLogxK
M3 - Article
C2 - 18160844
AN - SCOPUS:38049141251
VL - 39
SP - 733
EP - 745
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
SN - 1226-3613
IS - 6
ER -