title: Terminal sialylation is altered in airway cells with impaired CFTR-mediated chloride transport.
abstract: Reduced terminal sialylation at the surface of airway epithelial cells from patients with cystic fibrosis may predispose them to bacterial infection. To determine whether a lack of chloride transport or misprocessing of mutant cystic fibrosis transmembrane conductance regulator (CFTR) is critical for the alterations in glycosylation, we studied a normal human tracheal epithelial cell line (9/HTEo(-)) transfected with the regulatory (R) domain of CFTR, which blocks CFTR-mediated chloride transport; DeltaF508 CFTR, which is misprocessed, wild-type CFTR; or empty vector. Reduced cAMP-stimulated chloride transport is seen in the R domain and DeltaF508 transfectants. These two cell lines had consistent, significantly reduced binding of elderberry bark lectin, which recognizes terminal sialic acid in the alpha-2,6 configuration. Binding of other lectins, including Maakia amurensis lectin, which recognizes sialic acid in the alpha-2,3 configuration, was comparable in all cell lines. Because the cell surface change occurred in R domain-transfected cells, which continue to express wild-type CFTR, it cannot be related entirely to misprocessed or overexpressed CFTR. It is associated most closely with reduced CFTR activity.
authors.affiliation: Department of Pediatrics, Case Western Reserve University at Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA. dmk8@po.cwru.edu
authors.forename: D
authors.initials: D
authors.lastname: Kube
authors.forename: L
authors.initials: L
authors.lastname: Adams
authors.forename: A
authors.initials: A
authors.lastname: Perez
authors.forename: P B
authors.initials: PB
authors.lastname: Davis
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D004136:Dinitrobenzenes / Q000493:pharmacokinetics; D005809:Genes, Regulator / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000502:physiology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism; D012016:Reference Values; D014132:Trachea / Q000166:cytology / Q000378:metabolism*; D014162:Transfection
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D004136:Dinitrobenzenes; D037102:Lectins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C042432:3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine; D019158:N-Acetylneuraminic Acid