title: Pseudomonas aeruginosa induces vascular endothelial growth factor synthesis in airway epithelium in vitro and in vivo.
abstract: Pseudomonas aeruginosa (PA) airway infection and bronchial blood vessel proliferation are features of bronchiectasis. Because vascular endothelial growth factor (VEGF)-A regulates angiogenesis, we hypothesised that PA infection induces VEGF synthesis in epithelium and peribronchial angiogenesis. Because epidermal growth factor receptor (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. C57BL/6N mice were instilled intratracheally with sterile agarose beads or with agarose beads coated with the PA strain PAO1 (mean ± sem 6 × 10(5) ± 3 × 10(5) cfu · animal(-1)), with or without the EGFR inhibitor AG1478 (12.5 mg · kg(-1) · day(-1) intraperitoneally). 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.
authors: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, UPRES EA 2511, Paris, France.
authors: C
authors: C
authors: Martin
authors: G
authors: G
authors: Thévenot
authors: S
authors: S
authors: Danel
authors: J
authors: J
authors: Chapron
authors: A
authors: A
authors: Tazi
authors: J
authors: J
authors: Macey
authors: D J
authors: DJ
authors: Dusser
authors: I
authors: I
authors: Fajac
authors: P-R
authors: PR
authors: Burgel
mesh_terms: D000818:Animals; D001987:Bronchiectasis / Q000378:metabolism / Q000382:microbiology; D018277:Carcinoma, Mucoepidermoid; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000382:microbiology; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology; D020545:Respiratory Mucosa / Q000098:blood supply / Q000378:metabolism* / Q000382:microbiology*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D066246:ErbB Receptors