Increased sulfation of glycoconjugates by cultured nasal epithelial cells from patients with cystic fibrosis

P. W. Cheng, T. F. Boat, K. Cranfill, J. R. Yankaskas, R. C. Boucher

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

Cystic fibrosis (CF) respiratory epithelia exhibit abnormal anion transport that may be linked to abnormal lung defense. In these studies, we investigated whether primary cultures of CF respiratory epithelial cells regulate abnormally the sulfate content of high molecular weight glycoconjugates (HMG) participating in airways' mucosal defense. HMG, including glycosaminoglycans and mucin-type glycoproteins released spontaneously into medium and HMG released from cell surfaces by trypsin, were metabolically labeled with 35SO4(=) and [6-3H]glucosamine (GlcN) or 35SO4(=) and [3H]serine. All three classes of HMG from CF cells exhibited 35S/3H labeling ratios 1.5-4-fold greater than HMG from normal or disease control cells. Differences for labeling ratios of HMG from CF cells were shown to be the consequence of increased 35SO4(=) incorporation rather than decreased peptide synthesis and release or HMG glycosylation. The buoyant density of CF mucin-type HMG also was increased, consistent with increased sulfation. These observations suggest that oversulfation of a spectrum of HMG is a genetically determined characteristic of CF epithelial cells and may play an important pathophysiological role by altering the properties of mucous secretions and/or the interactions between selected bacteria and HMG at the airways' surface.

Original languageEnglish (US)
Pages (from-to)68-72
Number of pages5
JournalJournal of Clinical Investigation
Volume84
Issue number1
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Medicine(all)

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