title: Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice.
abstract: OBJECTIVE
  Cystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.
  
  
  METHODS
  CFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.
  
  
  RESULTS
  Pharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.
  
  
  CONCLUSIONS
  Lack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, HSW 825, 505 Parnassus AVE, San Francisco, CA 94143-0130, USA. suxiao1@yahoo.com
authors.forename: Xiao
authors.initials: X
authors.lastname: Su
authors.forename: Mark R
authors.initials: MR
authors.lastname: Looney
authors.forename: Hang Emily
authors.initials: HE
authors.lastname: Su
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D019005:Cystic Fibrosis Transmembrane Conductance Regulator