title: Identification of vitamin C transporters in the human airways: a cross-sectional in vivo study.
abstract: OBJECTIVE
  Vitamin C is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role as a sacrificial antioxidant, little is known about its transport into the respiratory tract lining fluid (RTLF), or the underlying airway epithelial cells. While several vitamin C transporters have been identified, such as sodium-ascorbate cotransporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting dehydroascorbate, knowledge of their protein distribution within the human lung is limited, in the case of GLUTs or unknown for SVCTs.
  
  
  METHODS
  Protein expression of vitamin C transporters (SVCT1/2 and GLUT1-4) was examined by immunohistochemistry in endobronchial biopsies, and by FACS in airway leucocytes from lavage fluid, obtained from 32 volunteers; 16 healthy and 16 mild asthmatic subjects. In addition, antioxidant concentrations were determined in RTLF. The study was performed at one Swedish centre.
  
  
  METHODS
  The primary outcome measure was to establish the location of vitamin C transporters in the human airways. As secondary outcome measures, RTLF vitamin C concentration was measured and related to transporter expression, as well as bronchial epithelial inflammatory and goblet cells numbers.
  
  
  RESULTS
  Positive staining was identified for SVCT1 and 2 in the vascular endothelium. SVCT2 and GLUT2 were present in the apical bronchial epithelium, where SVCT2 staining was predominately localised to goblet cells and inversely related to RTLF vitamin C concentrations.
  
  
  CONCLUSIONS
  This experimental study is the first to demonstrate protein expression of GLUT2 and SVCT2 in the human bronchial epithelium. A negative correlation between SVCT2-positive goblet cells and bronchial RTLF vitamin C concentrations suggests a possible role for goblet cells in regulating the extracellular vitamin C pool.
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors: Nirina
authors: N
authors: Larsson
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors: Gregory D
authors: GD
authors: Rankin
authors: MRC-PHE Centre for Environment & Health, Faculty of Life Sciences & Medicine, Kings College London, London, UK.
authors: Elif M
authors: EM
authors: Bicer
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors: Ester
authors: E
authors: Roos-Engstrand
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors: Jamshid
authors: J
authors: Pourazar
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors: Anders
authors: A
authors: Blomberg
authors: MRC-PHE Centre for Environment & Health, Faculty of Life Sciences & Medicine, Kings College London, London, UK.
authors: Ian S
authors: IS
authors: Mudway
authors: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors: Annelie F
authors: AF
authors: Behndig
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism*; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D021381:Protein Transport; D020545:Respiratory Mucosa / Q000378:metabolism*; D060347:Sodium-Coupled Vitamin C Transporters / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D001205:Ascorbic Acid