title: G551D CF mice display an abnormal host response and have impaired clearance of Pseudomonas lung disease.
abstract: Several cystic fibrosis (CF) mouse models demonstrate an increased susceptibility to Pseudomonas aeruginosa lung infection, characterized by excessive inflammation and high rates of mortality. Here we developed a model of chronic P. aeruginosa lung disease in mice homozygous for the murine CF transmembrane conductance regulator G551D mutation that provides an excellent model for CF lung disease. After 3 days of infection with mucoid P. aeruginosa entrapped in agar beads, the G551D animals lost substantially more body weight than non-CF control animals and were less able to control the infection, harboring over 40-fold more bacteria in the lung. The airways of infected G551D animals contained altered concentrations of the inflammatory mediators tumor necrosis factor-alpha, KC/N51, and macrophage inflammatory protein-2 during the first 2 days of infection, suggesting that an ineffective inflammatory response is partly responsible for the clearance defect.
authors.affiliation: Institute for Molecular Biosciences, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: McMorran
authors.forename: J S
authors.initials: JS
authors.lastname: Palmer
authors.forename: D P
authors.initials: DP
authors.lastname: Lunn
authors.forename: D
authors.initials: D
authors.lastname: Oceandy
authors.forename: E O
authors.initials: EO
authors.lastname: Costelloe
authors.forename: G R
authors.initials: GR
authors.lastname: Thomas
authors.forename: D A
authors.initials: DA
authors.lastname: Hume
authors.forename: B J
authors.initials: BJ
authors.lastname: Wainwright
mesh_terms: D000483:Alleles; D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002908:Chronic Disease; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000235:genetics* / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D006720:Homozygote; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D008171:Lung Diseases / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012016:Reference Values
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019005:Cystic Fibrosis Transmembrane Conductance Regulator