Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung.
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.
Lee
Chun Geun
CG
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, 441c TAC, New Haven, Connecticut 06520-8057, USA.
Link
Holger
H
Baluk
Peter
P
Homer
Robert J
RJ
Chapoval
Svetlana
S
Bhandari
Vineet
V
Kang
Min Jong
MJ
Cohn
Lauren
L
Kim
Yoon Keun
YK
McDonald
Donald M
DM
Elias
Jack A
JA
D000402:Airway Obstruction / Q000276:immunology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology*; D018793:Interleukin-13 / Q000276:immunology; D008168:Lung / Q000503:physiopathology* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D017931:DNA Primers; D018793:Interleukin-13; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A