title: Deletion of aquaporin 5 aggravates acute lung injury induced by Pseudomonas aeruginosa.
abstract: BACKGROUND
  Aquaporin (AQP) is a membrane protein that facilitates osmotic water transport. Aquaporin 5 (AQP5) expresses at type I alveolar epithelia of apical membrane that confers high osmotic water permeability. Osmosis or stretch challenge in alveoli significantly up-regulates AQP5 expression, which suggests that AQP5 may play a role in the maintenance of epithelia barrier function. Pseudomonas aeruginosa (PA), a leading gram-negative bacterial frequently isolated from ventilation-associated pneumonia patients, disrupts alveolar and airway epithelial cells and subsequently leads to blood dissemination. In this study, we hypothesized that AQP5 might be protective in acute lung injury induced by PA, and deletion of AQP5 might lead to aggravated lung injury.
  
  
  METHODS
  Lung injury model was induced by intratracheal instillation of PA (1 × 10(6) colony-forming unit) in wild-type and AQP5 knockout mice, 2 hours and 6 hours later, blood and lung lysate were cultured to detect blood dissemination, bronchoalveolar lavage fluid and lung tissue were collected for histology analysis. Lung injury assessment, wet/dry weight ratio, protein leakage, and Evan's blue dye extravasation were evaluated for pulmonary barrier function.
  
  
  RESULTS
  AQP5 deficiency led to increased bacterial blood dissemination and aggravated lung injury during PA infection, and AQP5 deletion also reduced mucin production in lung. Moreover, AQP5 deficiency showed declined activation of mitogen-activated protein kinase and nuclear factor-kappa B pathways in lungs before and after PA infection.
  
  
  CONCLUSIONS
  Our data demonstrated that AQP5 plays a protective role in the maintenance of pulmonary barrier function against PA infection.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Yuan-Lin
authors.initials: YL
authors.lastname: Song
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.forename: Chun-Xue
authors.initials: CX
authors.lastname: Bai
mesh_terms: D055371:Acute Lung Injury / Q000382:microbiology* / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D051402:Aquaporin 5 / Q000172:deficiency / Q000502:physiology*; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D005119:Extravasation of Diagnostic and Therapeutic Materials; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D011552:Pseudomonas Infections / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells
chemical_list: C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases