title: Electrophysiological evaluation of cystic fibrosis conductance transmembrane regulator (CFTR) expression in human monocytes.
abstract: BACKGROUND
  Cystic fibrosis is caused by mutations of CFTR gene, a protein kinase A-activated anion channel, and is associated to a persistent and excessive chronic lung inflammation, suggesting functional alterations of immune cells. Leukocytes express detectable levels of CFTR but the molecule has not been fully characterized in these cells.
  
  
  METHODS
  Freshly isolated monocytes from healthy individuals and CF patients were assessed by protein expression, single cell electrophysiological and membrane depolarization assays.
  
  
  RESULTS
  We recorded chloride currents by patch clamp in healthy monocytes, after the administration of a CFTR stimulus. Currents were sensitive to a specific blocker of the CFTR channel, CFTRinh-172 and were absent in CF monocytes. Next, we evaluated the effects of ex vivo exposure of monocytes from cystic fibrosis patients carrying the F508del mutation to a chemical corrector, Vertex-325. We found an increase in CFTR expression by confocal microscopy and a recovery of CFTR function by both patch clamp and single cell fluorescence analysis.
  
  
  CONCLUSIONS
  We confirm the expression of functional CFTR in human monocytes and demonstrate that blood monocytes can represent an adequate source of primary cells to assess new therapies and define diagnosis of CF.
  
  
  CONCLUSIONS
  Tests to evaluate CFTR functional abnormalities in CF disease might greatly benefit from the availability of a convenient source of primary cells. This electrophysiological study promotes the use of monocytes as a minimally invasive tool to study and monitor CFTR function in individual patients.
authors.affiliation: Department of Neurological and Movement Sciences, Section of Physiology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy; Center for Biomedical Computing, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Electronic address: michele.ettorre@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Ettorre
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy; Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Stefani 1, 37126 Verona, Italy.
authors.forename: Genny
authors.initials: G
authors.lastname: Verzè
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Caldrer
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy; Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Stefani 1, 37126 Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Calcaterra
authors.affiliation: Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Stefani 1, 37126 Verona, Italy.
authors.forename: Baroukh Maurice
authors.initials: BM
authors.lastname: Assael
authors.affiliation: Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Stefani 1, 37126 Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Melotti
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Sorio
authors.affiliation: Department of Neurological and Movement Sciences, Section of Physiology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy; Center for Biomedical Computing, University of Verona, Strada le Grazie 8, 37134 Verona, Italy; National Institute of Neuroscience, Verona, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Buffelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017384:Sequence Deletion
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Cystic Fibrosis Conductance; Cystic fibrosis; Leukocytes; Patch clamp; Transmembrane Regulator