1.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 ; Kyung Hoon MIN ; Chung Hyun CHO ; Gou Young KOH ; Ho Sung PARK ; Yong Chul LEE
Experimental & Molecular Medicine 2007;39(6):733-745
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.
Allergens/immunology
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Angiopoietin-1/genetics/pharmacology/*therapeutic use
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Animals
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Asthma/*prevention & control
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Bronchial Hyperreactivity/physiopathology/prevention & control
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Chemokines/metabolism
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Inflammation/pathology/*prevention & control
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Mice
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Mice, Inbred C57BL
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Recombinant Fusion Proteins/*therapeutic use
2.Angiogenic factors are associated with development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Di-min NIE ; Qiu-ling WU ; Xia-xia ZHU ; Ran ZHANG ; Peng ZHENG ; Jun FANG ; Yong YOU ; Zhao-dong ZHONG ; Ling-hui XIA ; Mei HONG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2015;35(5):694-699
Acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanisms of aGVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) in the development of aGVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1, Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro, endothelial cells (ECs) were treated with TNF-β in the presence or absence of Ang-1, and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT, Ang-1, Ang-2 and VEGF all exhibited significant variation, suggesting these factors might be involved in the endothelial damage in transplantation. Patients with aGVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without aGVHD, implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to aGVHD. In vitro, TNF-β promoted the release of Ang-2 by ECs and impaired tubule formation of ECs, which were both weakened by Ang-1, suggesting that Ang-1 may play a protective role in aGVHD by influencing the secretion of Ang-2, consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for aGVHD.
Acute Disease
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Adolescent
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Adult
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Angiogenesis Inducing Agents
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immunology
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metabolism
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pharmacology
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Angiopoietin-1
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genetics
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immunology
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pharmacology
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Angiopoietin-2
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genetics
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immunology
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pharmacology
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Antineoplastic Agents
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therapeutic use
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Female
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Gene Expression Regulation, Neoplastic
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Graft vs Host Disease
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genetics
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immunology
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pathology
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Hematopoietic Stem Cell Transplantation
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Human Umbilical Vein Endothelial Cells
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cytology
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drug effects
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immunology
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Humans
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Leukemia, Myeloid
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genetics
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immunology
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pathology
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therapy
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Lymphoma, Non-Hodgkin
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genetics
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immunology
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pathology
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therapy
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Male
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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genetics
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immunology
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pathology
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therapy
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Retrospective Studies
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Signal Transduction
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Transplantation, Homologous
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Tumor Necrosis Factor-alpha
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pharmacology
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Vascular Endothelial Growth Factor A
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genetics
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immunology