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.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Lee, K., Lee, K., Kim, S. et al. Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1. Exp Mol Med 39, 733–745 (2007). https://doi.org/10.1038/emm.2007.80
Published:
Issue Date:
DOI: https://doi.org/10.1038/emm.2007.80
Keywords
This article is cited by
-
Angiopoietin-2 concentration in serum is associated with severe asthma phenotype
Allergy, Asthma & Clinical Immunology (2016)
-
Angiopoietin-1 and Angiopoietin-2 in metabolic disorders: therapeutic strategies to restore the highs and lows of angiogenesis in diabetes
Journal of Endocrinological Investigation (2016)