Glycosylation of sputum mucins is altered in cystic fibrosis patients

Schulz, Benjamin L.; Sloane, Andrew J.; Robinson, Leanne J.; Prasad, Sindhu S.; Lindner, Robyn A.; Robinson, Michael E.; Bye, Peter T. P.; Nielson, Dennis W.; Harry, Jenny L.; Packer, Nicolle H.; Karlsson, Niclas G.

doi:10.1093/glycob/cwm036

Cited by 89 publications

(80 citation statements)

References 45 publications

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“…In this regard, mucus plugging the airways of an individual in status asthmaticus was enriched in the low-charged form of MUC5B (22). Altered glycosylation of mucins has previously been reported in airways disease (11,20,23). Because mucin glycans are known receptors for microorganisms, changes in glycosylation might favor bacterial colonization, increasing the risk of exacerbation and infection (24,25).…”

Section: Discussionmentioning

confidence: 93%

MUC5B Is the Major Mucin in the Gel Phase of Sputum in Chronic Obstructive Pulmonary Disease

Kirkham

Kolsum²,

Rousseau³

et al. 2008

Am J Respir Crit Care Med

125

127

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Rationale: Overproduction of mucus is a contributory factor in the progression of chronic obstructive pulmonary disease (COPD). The polymeric mucins are major macromolecules in the secretion. Therefore, we hypothesized that the polymeric mucin composition or properties may be different in the sputum from individuals with COPD and smokers without airflow obstruction. Objectives: To determine the major polymeric mucins in COPD sputum and whether these are different in the sputum from individuals with COPD compared with that from smokers without airflow obstruction. Methods: The polymeric mucin composition of sputum from patients with COPD and smokers without airflow obstruction was analyzed by Western blotting analysis. The tissue localization of the mucins was determined by immunohistochemistry, and their size distribution was analyzed by rate-zonal centrifugation. Measurements and Main Results: MUC5AC and MUC5B were the major mucins. MUC5AC was the predominant mucin in the smoker group, whereas MUC5B was more abundant from the patients with COPD, with a significant difference in the ratio of MUC5B to MUC5AC (P 5 0.004); this ratio was correlated with FEV 1 in the COPD group (r 5 0.63; P 5 0.01). The lower-charged glycosylated form of MUC5B was more predominant in COPD (P 5 0.012). No significant associations were observed with respect to sex, age, or pack-year history. In both groups, MUC5AC was produced by surface epithelial cells and MUC5B by submucosal gland cells. Finally, there was a shift toward smaller mucins in the COPD group. Conclusions: Our data indicate that there are differences in mucin amounts and properties between smokers with and without COPD. Further studies are needed to examine how this may impact disease progression.

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Section: Discussionmentioning

confidence: 93%

MUC5B Is the Major Mucin in the Gel Phase of Sputum in Chronic Obstructive Pulmonary Disease

Kirkham

Kolsum²,

Rousseau³

et al. 2008

Am J Respir Crit Care Med

125

127

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“…A number of studies have explored the biomechanical properties of CF mucus (Charman & Reid 1972;King 1981;Nielsen et al 2004;Perez-Vilar & Boucher 2004;Rubin 2007). While it is difficult to compare the results of these studies owing to differences in measurement techniques, it is clear that mucous viscosity varies among patients and over time within patients (App et al 1998;Rubin 2007;Schulz et al 2007). Furthermore, mucolytic substances are commonly prescribed to aid mucociliary clearance (Shak et al 1990;Shak 1995;Donaldson et al 2006;Evans & Koo 2009).…”

Section: Discussionmentioning

confidence: 99%

Viscous medium promotes cooperation in the pathogenic bacteriumPseudomonas aeruginosa

et al. 2009

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There has been extensive theoretical debate over whether population viscosity (limited dispersal) can favour cooperation. While limited dispersal increases the probability of interactions occurring between relatives, which can favour cooperation, it can also lead to an increase in competition between relatives and this can reduce or completely negate selection for cooperation. Despite much theoretical attention, there is a lack of empirical research investigating these issues. We cultured Pseudomonas aeruginosa bacteria in medium with different degrees of viscosity and examined the fitness consequences for a cooperative trait-the production of iron-scavenging siderophore molecules. We found that increasing viscosity of the growth medium (i) significantly limited bacterial dispersal and the diffusion of siderophore molecules and (ii) increased the fitness of individuals that produced siderophores relative to mutants that did not. We propose that viscosity favours siderophore-producing individuals in this system, because the benefits of siderophore production are more likely to accrue to relatives (i.e. greater indirect benefits), and, at the same time, bacteria are more likely to gain direct fitness benefits by taking up siderophore molecules produced by themselves (i.e. the trait becomes less cooperative). Our results suggest that viscosity of the microbial growth environment is a crucial factor determining the dynamics of wild-type bacteria and siderophore-deficient mutants in natural habitats, such as the viscous mucus in cystic fibrosis lung.

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“…Glycan structures are modified during glycoprotein traffic through the Golgi, and the final structures present on mature glycoproteins can play important roles in regulating protein function [1,11]. Changes in the structure of glycans attached to proteins are also associated with numerous diseases [12,13,14,15].…”

Section: Introductionmentioning

confidence: 99%

Mixed disulfide formation in vitro between a glycoprotein substrate and yeast oligosaccharyltransferase subunits Ost3p and Ost6p

Yusuf

Bailey

Tan

et al. 2013

Biochemical and Biophysical Research Communications

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Glycosylation of sputum mucins is altered in cystic fibrosis patients

Cited by 89 publications

References 45 publications

MUC5B Is the Major Mucin in the Gel Phase of Sputum in Chronic Obstructive Pulmonary Disease

MUC5B Is the Major Mucin in the Gel Phase of Sputum in Chronic Obstructive Pulmonary Disease

Viscous medium promotes cooperation in the pathogenic bacteriumPseudomonas aeruginosa

Mixed disulfide formation in vitro between a glycoprotein substrate and yeast oligosaccharyltransferase subunits Ost3p and Ost6p

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