title: Nasal epithelial cells as surrogates for bronchial epithelial cells in airway inflammation studies.
abstract: The nose is an attractive source of airway epithelial cells, particularly in populations in which bronchoscopy may not be possible. However, substituting nasal cells for bronchial epithelial cells in the study of airway inflammation depends upon comparability of responses, and evidence for this is lacking. Our objective was to determine whether nasal epithelial cell inflammatory mediator release and receptor expression reflect those of bronchial epithelial cells. Paired cultures of undifferentiated nasal and bronchial epithelial cells were obtained from brushings from 35 subjects, including 5 children. Cells were subject to morphologic and immunocytochemical assessment. Mediator release from resting and cytokine-stimulated cell monolayers was determined, as was cell surface receptor expression. Nasal and bronchial cells had identical epithelial morphology and uniform expression of cytokeratin 19. There were no differences in constitutive expression of CD44, intercellular adhesion molecule-1, alphavbeta3, and alphavbeta5. Despite significantly higher constitutive release of IL-8, IL-6, RANTES (regulated on activation, normal T cell expressed and secreted), and matrix metalloproteinase (MMP)-9 from nasal compared with bronchial cells, the increments in release of all studied mediators in response to stimulation with IL-1beta and TNF-alpha were similar, and there were significant positive correlations between nasal and bronchial cell secretion of IL-6, RANTES, vascular endothelial growth factor, monocyte chemoattractant protein-1, MMP-9, and tissue inhibitor of metalloproteinase-1. Despite differences in absolute mediator levels, the responses of nasal and bronchial epithelial cells to cytokine stimulation were similar, expression of relevant surface receptors was comparable, and there were significant correlations between nasal and bronchial cell mediator release. Therefore, nasal epithelial cultures constitute an accessible surrogate for studying lower airway inflammation.
authors.affiliation: School of Medicine, University of Aberdeen, Royal Aberdeen Children's Hospital, Aberdeen, UK. catherine.mcdougall@luht.scot.nhs.uk
authors.forename: Catherine M
authors.initials: CM
authors.lastname: McDougall
authors.forename: Morgan G
authors.initials: MG
authors.lastname: Blaylock
authors.forename: J Graham
authors.initials: JG
authors.lastname: Douglas
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Brooker
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Helms
authors.forename: Garry M
authors.initials: GM
authors.lastname: Walsh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D048430:Cell Shape; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D009666:Nose / Q000166:cytology* / Q000187:drug effects
chemical_list: D016207:Cytokines