Glycobiology Advance Access originally published online on March 28, 2007
Glycobiology 2007 17(7):698-712; doi:10.1093/glycob/cwm036
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Glycosylation of sputum mucins is altered in cystic fibrosis patients
2 Proteome Systems Ltd, Unit 1, 35-41 Waterloo Road, North Ryde, Sydney, NSW 2113, Australia
3 Department of Respiratory Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW 2050, Australia
4 Department of Pediatric Pulmonary Medicine, University of California-San Francisco, San Francisco, CA 94143-0632
1 To whom correspondence should be addressed; Tel: +61 2 9850 8176; Fax: +61 2 9850 8313; E-mail: nicki.packer{at}mq.edu.au
Received on October 10, 2006; revised on March 13, 2006; accepted on March 20, 2007
Cystic fibrosis (CF) is characterized by chronic lung infection and inflammation, with periods of acute exacerbation causing severe and irreversible lung tissue damage. We used protein and glycosylation analysis of high-molecular mass proteins in saline-induced sputum from CF adults with and without an acute exacerbation, CF children with stable disease and preserved lung function, and healthy non-CF adult and child controls to identify potential biomarkers of lung condition. While the main high-molecular mass proteins in the sputum from all subjects were the mucins MUC5B and MUC5AC, these appeared degraded in CF adults with an exacerbation. The glycosylation of these mucins also showed reduced sulfation, increased sialylation, and reduced fucosylation in CF adults compared with controls. Despite improvements in pulmonary function after hospitalization, these differences remained. Two CF children showed glycoprotein profiles similar to those of CF adults with exacerbations and also presented with pulmonary flares shortly after sampling, while the remaining CF children had profiles indistinguishable from those of healthy non-CF controls. Sputum mucin glycosylation and degradation are therefore not inherently different in CF, and may also be useful predictive biomarkers of lung condition.
Key words: mucin / O-glycosylation/mass spectrometry / cystic fibrosis / pulmonary exacerbation
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