%0 Journal Article %A C. Martin %A G. Thévenot %A S. Danel %A J. Chapron %A A. Tazi %A J. Macey %A D.J. Dusser %A I. Fajac %A P-R. Burgel %T Pseudomonas aeruginosa induces VEGF synthesis in airway epithelium in vitro and in vivo %D 2011 %R 10.1183/09031936.00134910 %J European Respiratory Journal %P erj01349-2010 %X Pseudomonas aeruginosa (PA) airway infection and bronchial blood vessel proliferation are features of bronchiectasis. Because vascular endothelial growth factor-A (VEGF) regulates angiogenesis, we hypothesized that PA infection induces VEGF synthesis in epithelium and peribronchial angiogenesis. Because EGF receptors (EGFR) activation regulates VEGF synthesis in cancer, we also evaluated the roles of EGFR.Airway epithelial cells were incubated for 24 h with PA supernatants and VEGF concentrations were measured in culture medium by ELISA. C57/Bl6 mice were instilled intratracheally with sterile or with PAO1-coated (6.105±3.105CFU/animal) agarose beads with or without the EGFR inhibitor AG1478 (12.5 mg·kg/d−1, i.p.). Epithelial immunostaining for VEGF and phosphorylated EGFR, and peribronchial vascularity were quantified using morphometric analysis. VEGF expression was further assessed by western blot in mouse lung homogenates.PA supernatants induced dose-dependent VEGF synthesis in cultured airway epithelial cells, effects which were prevented by EGFR antagonists. In mice, persistent PAO1 infection increased immunostaining for VEGF and phosphorylated EGFR in airway epithelium, and resulted in increased peribronchial vascularity within 7 days. These effects were reduced by EGFR inhibition.Persistent PA infection induced VEGF synthesis in airway epithelium and peribronchial angiogenesis, at least in part, via EGFR-dependent mechanisms. %U https://erj.ersjournals.com/content/erj/early/2011/03/24/09031936.00134910.full.pdf