title: Monocyte derived macrophages from CF pigs exhibit increased inflammatory responses at birth.
abstract: BACKGROUND
  We sought to address whether CF macrophages have a primary functional defect as a consequence of CFTR loss and thus contribute to the onset of infection and inflammation observed in CF lung disease.
  
  
  METHODS
  Monocyte derived macrophages (MDMs) were prepared from newborn CF and non-CF pigs. CFTR mRNA expression was quantified by rtPCR and anion channel function was determined using whole cell patch clamp analysis. IL8 and TNFα release from MDMs in response to lipopolysaccharide stimulation was measured by ELISA.
  
  
  RESULTS
  CFTR was expressed in MDMs by Q-rtPCR at a lower level than in epithelial cells. MDMs exhibited functional CFTR current at the cell membrane and this current was absent in CF MDMs. CF MDMs demonstrated an exaggerated response to lipopolysaccharide stimulation.
  
  
  CONCLUSIONS
  In the absence of CFTR function, macrophages from newborn CF pigs exhibit an increased inflammatory response to a lipopolysaccharide challenge. This may contribute to the onset and progression of CF lung disease.
authors.affiliation: Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Paemka
authors.affiliation: Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Brian N
authors.initials: BN
authors.lastname: McCullagh
authors.affiliation: Department of Internal Medicine, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Mahmoud H
authors.initials: MH
authors.lastname: Abou Alaiwa
authors.affiliation: Department of Internal Medicine, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.affiliation: Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Christoph O
authors.initials: CO
authors.lastname: Randak
authors.affiliation: Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; MRC/University of Edinburgh Centre for Inflammation Research, Edinburgh, Scotland, UK. Electronic address: r.d.gray@ed.ac.uk.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gray
authors.affiliation: Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. Electronic address: paul-mccray@uiowa.edu.
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003550:Cystic Fibrosis / Q000235:genetics / Q000276:immunology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D007114:Immunization / Q000379:methods; D007249:Inflammation / Q000276:immunology*; D016209:Interleukin-8 / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D018408:Patch-Clamp Techniques / Q000379:methods; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CFTR; Inflammation; Lipopolysaccharide; Macrophage; Monocyte