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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Altered sialyl- and fucosyl-linkage on mucins in cystic fibrosis patients promotes formation of the sialyl-Lewis X determinant on salivary MUC-5B and MUC-7.

Destruction of the lungs as a consequence of recurrent infections with microorganisms such as Pseudomonas aeruginosa remains the underlying cause of most morbidity and mortality in cystic fibrosis (CF). We have hypothesized that changes in the glycosylation of key tracheal mucins such as MUC5B and MUC7 might increase the risk of pulmonary disease in CF patients. However, in preference to sputum we have examined the sugar-chains on these mucins in saliva because in the latter not only can the glycoproteins be collected from controls, but they are essentially free from modifications made following bacterial infection in disease. Proteins in ductal or whole-mouth saliva from 20 CF patients with the Delta F-508 CFTR mutation and age-and sex-matched controls were separated by SDS-PAGE and blotted onto nitrocellulose and then probed with labelled lectins of known specificity. Linkage of terminal sialic acid on the blotted mucins was determined using Sambucus nigra agglutinin (detects the 2-->6 linkage) and Maackia amurensis agglutinin (the 2-->3 linkage). Fucose was detected by Ulex europaeus agglutinin-1 (1-->2 linkage) and Aleuria aurantia agglutinin (1-->3 linkage). We found that each mucin shows a characteristic glycosylation pattern and in controls most of the sialic acid is 2-->6 linked on MG1 (MUC 5B) and 2-->3 linked on MG2 (MUC 7). CF is associated with a shift from a 2-->6 linkage to a 2-->3 linkage on MG1 with some patients showing almost no 2-->6 linkage; 2-->3 linkage on MG2 is similarly increased in disease in some individuals. The expression of fucose on these mucins is also raised in CF patients. These shift to a 2-->3 linkage of sialic acid, and with increased fucosylation this promotes the formation of sialyl-Lewis X antigen detected on CF mucins in our study. These changes will be tested for their correlation with the severity of lung disease. We gratefully acknowledge support from the European Union Biomed-II Programme.[1]

References

  1. Altered sialyl- and fucosyl-linkage on mucins in cystic fibrosis patients promotes formation of the sialyl-Lewis X determinant on salivary MUC-5B and MUC-7. Shori, D.K., Genter, T., Hansen, J., Koch, C., Wyatt, H., Kariyawasam, H.H., Knight, R.A., Hodson, M.E., Kalogeridis, A., Tsanakas, I. Pflugers Arch. (2001) [Pubmed]
 
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