title: Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea.
abstract: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding for the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Several organs are affected in CF, but most of the morbidity and mortality comes from lung disease. Recent data show that the initial consequence of CFTR mutation is the failure to eradicate bacteria before the development of inflammation and airway remodeling. Bacterial clearance depends on a layer of airway surface liquid (ASL) consisting of both a mucus layer that traps, kills, and inactivates bacteria and a periciliary liquid layer that keeps the mucus at an optimum distance from the underlying epithelia, to maximize ciliary motility and clearance of bacteria. The airways in CF patients and animal models of CF demonstrate abnormal ASL secretion and reduced antimicrobial properties. Thus, it has been proposed that abnormal ASL secretion in response to bacteria may facilitate the development of the infection and inflammation that characterize CF airway disease. Whether the inhalation of bacteria triggers ASL secretion, and the role of CFTR, have never been tested, however. We developed a synchrotron-based imaging technique to visualize the ASL layer and measure the effect of bacteria on ASL secretion. We show that the introduction of Pseudomonas aeruginosa and other bacteria into the lumen of intact isolated swine tracheas triggers CFTR-dependent ASL secretion by the submucosal glands. This response requires expression of the bacterial protein flagellin. In patients with CF, the inhalation of bacteria would fail to trigger ASL secretion, leading to infection and inflammation.
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5;
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Luan
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5;
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Campanucci
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5;
authors.forename: Manoj
authors.initials: M
authors.lastname: Nair
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5;
authors.forename: Orhan
authors.initials: O
authors.lastname: Yilmaz
authors.affiliation: Canadian Light Source Inc., Saskatoon, SK, Canada S7N 2V3;
authors.forename: George
authors.initials: G
authors.lastname: Belev
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and.
authors.forename: Terry E
authors.initials: TE
authors.lastname: Machen
authors.affiliation: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Dean
authors.initials: D
authors.lastname: Chapman
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5; juan.ianowski@usask.ca.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Ianowski
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000276:immunology / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006193:Haemophilus influenzae / Q000378:metabolism; D007113:Immunity, Innate / Q000502:physiology; D008297:Male; D009077:Mucins / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000378:metabolism; D013552:Swine; D017356:Synchrotrons; D014132:Trachea / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*
chemical_list: D009077:Mucins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator