Abstract |
Exaggerated levels of VEGF ( vascular endothelial growth factor) are present in persons with asthma, but the role(s) of VEGF in normal and asthmatic lungs has not been defined. We generated lung-targeted VEGF(165) transgenic mice and evaluated the role of VEGF in T-helper type 2 cell (T(H)2)-mediated inflammation. In these mice, VEGF induced, through IL-13-dependent and -independent pathways, an asthma-like phenotype with inflammation, parenchymal and vascular remodeling, edema, mucus metaplasia, myocyte hyperplasia and airway hyper-responsiveness. VEGF also enhanced respiratory antigen sensitization and T(H)2 inflammation and increased the number of activated DC2 dendritic cells. In antigen-induced inflammation, VEGF was produced by epithelial cells and preferentially by T(H)2 versus T(H)1 cells. In this setting, it had a critical role in T(H)2 inflammation, cytokine production and physiologic dysregulation. Thus, VEGF is a mediator of vascular and extravascular remodeling and inflammation that enhances antigen sensitization and is crucial in adaptive T(H)2 inflammation. VEGF regulation may be therapeutic in asthma and other T(H)2 disorders.
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Authors | Chun Geun Lee, Holger Link, Peter Baluk, Robert J Homer, Svetlana Chapoval, Vineet Bhandari, Min Jong Kang, Lauren Cohn, Yoon Keun Kim, Donald M McDonald, Jack A Elias |
Journal | Nature medicine
(Nat Med)
Vol. 10
Issue 10
Pg. 1095-103
(Oct 2004)
ISSN: 1078-8956 [Print] United States |
PMID | 15378055
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cytokines
- DNA Primers
- Interleukin-13
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
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Topics |
- Airway Obstruction
(immunology, physiopathology)
- Analysis of Variance
- Animals
- Asthma
(physiopathology)
- Cytokines
(biosynthesis, immunology)
- DNA Primers
- Dendritic Cells
(immunology)
- Humans
- Hypersensitivity
(immunology, physiopathology)
- Interleukin-13
(immunology)
- Lung
(physiopathology, ultrastructure)
- Mice
- Mice, Transgenic
- Microscopy, Electron
- Neovascularization, Pathologic
(metabolism)
- Polymerase Chain Reaction
- T-Lymphocytes, Helper-Inducer
(immunology, metabolism)
- Vascular Endothelial Growth Factor A
(immunology, metabolism)
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