Mucin glycosylation changes in cystic fibrosis lung disease are not manifest in submucosal gland secretions

Benjamin L. Schulz, Andrew J. Sloane*, Leanne J. Robinson, Lucille T. Sebastian, Allan R. Glanville, Yuanlin Song, Alan S. Verkman, Jenny L. Harry, Nicolle H. Packer, Niclas G. Karlsson

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

SMG (submucosal gland) secretions are a major component of the airway surface liquid, are associated with innate immunity in the lung, and have been reported to be altered in lung disease. Changes in lung mucosal glycosylation have been reported in CF (cystic fibrosis), which may be responsible for differential bacterial binding to glycosylated components in the lung mucosa and hence increased pre-disposition to pulmonary infection. Glycoproteomic analysis was performed on SMG secretions collected from explanted bronchial tissue of subjects with severe lung disease, with and without CF, and controls without lung disease. Mucins MUC5B and MUC5AC were shown to be the dominant high-molecular-mass glycoprotein components, with a minor non-mucin glycoprotein component, gp-340, also present. Oligosaccharides containing blood-group determinants corresponding to subjects' blood type were abundant on MUC5B/MUC5AC, as were Lewis-type epitopes and their sialylated analogues, which are ligands for pathogens and leucocytes. No significant differences were found in the glycosylation of MUC5B/MUC5AC or gp-340 between CF and non-CF subjects with severe lung disease, implying that CF does not influence SMG secretion mucin glycosylation in end-stage lung disease. There were also no significant differences found in the glycosylation of these components in severe lung disease compared with non-diseased lungs. This suggests that previously reported changes in the glycosylation of respiratory glycoconjugates in CF, and other pulmonary conditions, are not due to the glycosylation of components in SMG secretions, but may involve other secretions, responses or extracellular factors.

Original languageEnglish
Pages (from-to)911-919
Number of pages9
JournalBiochemical Journal
Volume387
Issue number3
DOIs
Publication statusPublished - 1 May 2005
Externally publishedYes

Keywords

  • Cystic fibrosis
  • Glycosylation
  • Inflammation
  • Mass spectrometry (MS)
  • Mucin
  • Submucosal gland secretions

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    Schulz, B. L., Sloane, A. J., Robinson, L. J., Sebastian, L. T., Glanville, A. R., Song, Y., ... Karlsson, N. G. (2005). Mucin glycosylation changes in cystic fibrosis lung disease are not manifest in submucosal gland secretions. Biochemical Journal, 387(3), 911-919. https://doi.org/10.1042/BJ20041641