title: Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor.
abstract: BACKGROUND
  Ivacaftor improves clinical outcome by potentiation of mutant G551D CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils (PMNs), we hypothesized that ivacaftor may impact leukocyte activation.
  
  
  METHODS
  We examined blood leukocytes from G551D CF subjects prior to and at one and six months after receiving ivacaftor. Blood leukocytes from ivacaftor-naïve G551D, F508del, and healthy controls were also treated with ivacaftor ex vivo to assess mutation-specific effects.
  
  
  RESULTS
  Compared to healthy controls, G551D CF subjects had significantly higher expression of active CD11b on PMNs and of CD63 on monocytes, which were normalized by in vivo ivacaftor treatment. Ex vivo exposure to ivacaftor of blood cells from G551D, but not F508del and healthy subjects, resulted in changes in CXCR2 and CD16 expression on PMNs.
  
  
  CONCLUSIONS
  In vivo and ex vivo exposure of G551D CF leukocytes to ivacaftor resulted in an altered activation profile, suggesting mutation-specific leukocyte modulation.
authors.affiliation: Department of Medicine and Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, 424 THT, 1900 University Blvd, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, University of Alabama at Birmingham, MCLM 760, 1918 University Blvd, Birmingham, AL 35294, USA. Electronic address: bratcher@uab.edu.
authors.forename: Preston E
authors.initials: PE
authors.lastname: Bratcher
authors.affiliation: Department of Medicine and Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, 424 THT, 1900 University Blvd, Birmingham, AL 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, MCLM 790, 1918 University Blvd, Birmingham, AL 35294, USA; University of Alabama at Birmingham, UAB Lung Health Center, 526 20th Street South, Birmingham, AL 35294, USA; Department of Pediatrics at Children's of Alabama, University of Alabama at Birmingham, 1600 7th Avenue South, Birmingham, AL 35233, USA; Department of Cell, Developmental, and Integrative Biology, THT 926, 1720 2nd Avenue South, Birmingham, AL 35294, USA. Electronic address: smrowe@uab.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
authors.affiliation: Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, MCLM 790, 1918 University Blvd, Birmingham, AL 35294, USA; Department of Pediatrics at Children's of Alabama, University of Alabama at Birmingham, 1600 7th Avenue South, Birmingham, AL 35233, USA. Electronic address: greeves@peds.uab.edu.
authors.forename: Ginger
authors.initials: G
authors.lastname: Reeves
authors.affiliation: Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, MCLM 790, 1918 University Blvd, Birmingham, AL 35294, USA; Department of Pediatrics at Children's of Alabama, University of Alabama at Birmingham, 1600 7th Avenue South, Birmingham, AL 35233, USA. Electronic address: troberts@peds.uab.edu.
authors.forename: Tambra
authors.initials: T
authors.lastname: Roberts
authors.affiliation: Department of Medicine and Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, 424 THT, 1900 University Blvd, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, University of Alabama at Birmingham, MCLM 760, 1918 University Blvd, Birmingham, AL 35294, USA. Electronic address: szultom@uab.edu.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szul
authors.affiliation: Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, MCLM 790, 1918 University Blvd, Birmingham, AL 35294, USA; Department of Pediatrics at Children's of Alabama, University of Alabama at Birmingham, 1600 7th Avenue South, Birmingham, AL 35233, USA; Program in Protease and Matrix Biology, University of Alabama at Birmingham, MCLM 760, 1918 University Blvd, Birmingham, AL 35294, USA. Electronic address: tharris@peds.uab.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Harris
authors.affiliation: Program in Protease and Matrix Biology, University of Alabama at Birmingham, MCLM 760, 1918 University Blvd, Birmingham, AL 35294, USA; Department of Pediatrics, Emory University, 2015 Uppergate Drive, Room 344, Atlanta, GA 30322, USA; Center for Cystic Fibrosis and Airway Disease Research, Children's Healthcare of Atlanta, 2015 Uppergate Drive, Room 344, Atlanta, GA 30322, USA. Electronic address: tirouvanziam@emory.edu.
authors.forename: Rabindra
authors.initials: R
authors.lastname: Tirouvanziam
authors.affiliation: Department of Medicine and Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, 424 THT, 1900 University Blvd, Birmingham, AL 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, MCLM 790, 1918 University Blvd, Birmingham, AL 35294, USA; University of Alabama at Birmingham, UAB Lung Health Center, 526 20th Street South, Birmingham, AL 35294, USA; Medicine Service, United States Department of Veterans Affairs Medical Center, 700 19th Street South, Birmingham, AL 35233, USA; Program in Protease and Matrix Biology, University of Alabama at Birmingham, MCLM 760, 1918 University Blvd, Birmingham, AL 35294, USA. Electronic address: agaggar1@uab.edu.
authors.forename: Amit
authors.initials: A
authors.lastname: Gaggar
mesh_terms: D000328:Adult; D000627:Aminophenols / Q000008:administration & dosage*; D039481:CD11b Antigen / Q000032:analysis*; D065101:Chloride Channel Agonists / Q000008:administration & dosage; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009154:Mutation; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D015363:Quinolones / Q000008:administration & dosage*; D013223:Statistics as Topic; D060149:Tetraspanin 30 / Q000032:analysis*
chemical_list: D000627:Aminophenols; D039481:CD11b Antigen; C505032:CFTR protein, human; D065101:Chloride Channel Agonists; D015363:Quinolones; D060149:Tetraspanin 30; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: Blood; CFTR; G551D; Ivacaftor; Leukocyte; VX-770