title: MUC5B is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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 = 0.004); this ratio was correlated with FEV(1) in the COPD group (r = 0.63; P = 0.01). The lower-charged glycosylated form of MUC5B was more predominant in COPD (P = 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.
authors.affiliation: 1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Kirkham
authors.forename: Umme
authors.initials: U
authors.lastname: Kolsum
authors.forename: Karine
authors.initials: K
authors.lastname: Rousseau
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: David J
authors.initials: DJ
authors.lastname: Thornton
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D055257:Mucin-5B / Q000032:analysis*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012907:Smoking; D013183:Sputum / Q000737:chemistry*
chemical_list: C524678:MUC5AC protein, human; C524578:MUC5B protein, human; D055271:Mucin 5AC; D055257:Mucin-5B
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