Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation.

Détails

ID Serval
serval:BIB_D8644689FB29
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation.
Périodique
Journal of Clinical Investigation
Auteur(s)
Baluk P., Tammela T., Ator E., Lyubynska N., Achen M.G., Hicklin D.J., Jeltsch M., Petrova T.V., Pytowski B., Stacker S.A., Ylä-Herttuala S., Jackson D.G., Alitalo K., McDonald D.M.
ISSN
0021-9738 (Print)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2005
Volume
115
Numéro
2
Pages
247-257
Langue
anglais
Résumé
Edema occurs in asthma and other inflammatory diseases when the rate of plasma leakage from blood vessels exceeds the drainage through lymphatic vessels and other routes. It is unclear to what extent lymphatic vessels grow to compensate for increased leakage during inflammation and what drives the lymphangiogenesis that does occur. We addressed these issues in mouse models of (a) chronic respiratory tract infection with Mycoplasma pulmonis and (b) adenoviral transduction of airway epithelium with VEGF family growth factors. Blood vessel remodeling and lymphangiogenesis were both robust in infected airways. Inhibition of VEGFR-3 signaling completely prevented the growth of lymphatic vessels but not blood vessels. Lack of lymphatic growth exaggerated mucosal edema and reduced the hypertrophy of draining lymph nodes. Airway dendritic cells, macrophages, neutrophils, and epithelial cells expressed the VEGFR-3 ligands VEGF-C or VEGF-D. Adenoviral delivery of either VEGF-C or VEGF-D evoked lymphangiogenesis without angiogenesis, whereas adenoviral VEGF had the opposite effect. After antibiotic treatment of the infection, inflammation and remodeling of blood vessels quickly subsided, but lymphatic vessels persisted. Together, these findings suggest that when lymphangiogenesis is impaired, airway inflammation may lead to bronchial lymphedema and exaggerated airflow obstruction. Correction of defective lymphangiogenesis may benefit the treatment of asthma and other inflammatory airway diseases.
Mots-clé
Adenoviridae, Airway Obstruction, Animals, Bronchi/blood supply, Bronchi/metabolism, Chronic Disease, Dendritic Cells/metabolism, Dendritic Cells/pathology, Endothelial Growth Factors, Gene Expression Regulation/genetics, Hyperplasia/microbiology, Hyperplasia/pathology, Inflammation/genetics, Inflammation/metabolism, Lymph Nodes/metabolism, Lymph Nodes/pathology, Lymphatic Vessels/metabolism, Lymphatic Vessels/pathology, Macrophages, Alveolar/metabolism, Macrophages, Alveolar/pathology, Mice, Mice, Inbred C3H, Mycoplasma Infections/metabolism, Mycoplasma Infections/pathology, Mycoplasma pulmonis, Neovascularization, Pathologic/genetics, Neovascularization, Pathologic/metabolism, Neutrophils/metabolism, Neutrophils/pathology, Pulmonary Edema/genetics, Pulmonary Edema/microbiology, Respiratory Mucosa/metabolism, Respiratory Mucosa/microbiology, Signal Transduction/genetics, Vascular Endothelial Growth Factor C/genetics, Vascular Endothelial Growth Factor C/metabolism, Vascular Endothelial Growth Factor D/genetics, Vascular Endothelial Growth Factor D/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/12/2012 15:47
Dernière modification de la notice
20/08/2019 15:57
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