Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1.
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.
Lee
Kyung Sun
KS
Department of Internal Medicine, Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Lee
Ka Young
KY
Kim
So Ri
SR
Park
Hee Sun
HS
Park
Seoung Ju
SJ
Min
Kyung Hoon
KH
Cho
Chung-Hyun
CH
Koh
Gou Young
GY
Park
Ho Sung
HS
Lee
Yong Chul
YC
D000485:Allergens / Q000276:immunology; D042683:Angiopoietin-1 / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control; D018925:Chemokines / Q000378:metabolism; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
D000485:Allergens; D042683:Angiopoietin-1; C515576:COMP-Ang1 fusion protein; D018925:Chemokines; D011993:Recombinant Fusion Proteins