title: Response to acute lung infection with mucoid Pseudomonas aeruginosa in cystic fibrosis mice.
abstract: BACKGROUND
  Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator gene, which codes for a chloride channel, but the role of this chloride channel in inflammation induced by lung infection with Pseudomonas aeruginosa remains to be defined.
  
  
  OBJECTIVE
  We tested the hypothesis that loss of this chloride channel alone is sufficient to cause excessive inflammation in response to inflammatory stimuli.
  
  
  METHODS
  We investigated the response of cystic fibrosis and wild-type mice to mucoid P. aeruginosa administered by insufflation.
  
  
  METHODS
  The host responses measured included survival, weight change, lung morphometry, bacterial clearance, and inflammatory mediators, and cell counts were assessed in bronchoalveolar lavage fluid.
  
  
  RESULTS
  Depending on the dose administered and frequency of dosing, cystic fibrosis mice experienced significantly higher mortality rates, greater weight loss, higher lung pathology scores, and higher inflammatory mediator and neutrophil levels compared with wild-type mice, even after the bacteria had been cleared. Surprisingly, bacteria were cleared just as rapidly in cystic fibrosis mice as in wild-type mice, and sepsis was not observed. Chronic lung infections could not be established with mucoid P. aeruginosa in either cystic fibrosis or wild-type mice.
  
  
  CONCLUSIONS
  Absence of this chloride channel alone appears sufficient for exaggerated inflammation and excess mortality compared with wild-type controls in the face of mucoid P. aeruginosa lung infection. To establish chronic infection, additional factors such as bacterial trapping or poor clearance may be required.
authors.affiliation: Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, OH, USA. anna.vanheeckeren@case.edu
authors.forename: Anna M
authors.initials: AM
authors.lastname: van Heeckeren
authors.forename: Mark D
authors.initials: MD
authors.lastname: Schluchter
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Davis
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D020297:Mice, Congenic; D018181:Mice, Inbred CFTR; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016207:Cytokines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator