MUC5B is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease.
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.
Kirkham
Sara
S
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Kolsum
Umme
U
Rousseau
Karine
K
Singh
Dave
D
Vestbo
Jørgen
J
Thornton
David J
DJ
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*
C524678:MUC5AC protein, human; C524578:MUC5B protein, human; D055271:Mucin 5AC; D055257:Mucin-5B
Eur J Clin Invest. 2002 Jul;32(7):519-27
12153553
Methods Mol Biol. 2000;125:77-85
10820751
Br J Pharmacol. 2006 Sep;149(1):92-9
16880764
Biochem J. 1990 Jan 1;265(1):179-86
2302164
Clin Microbiol Rev. 2001 Apr;14(2):336-63
11292642
Am J Respir Cell Mol Biol. 1999 Feb;20(2):209-18
9922211
Chest. 2006 Oct;130(4):1102-8
17035444
Biochem J. 1999 Dec 1;344 Pt 2:321-30
10567212
Ann N Y Acad Sci. 2007 Sep;1112:140-53
17496063
Thorax. 2004 Dec;59(12):1032-40
15563701
Annu Rev Physiol. 2008;70:459-86
17850213
Biochem J. 2002 Feb 1;361(Pt 3):537-46
11802783
Eur Respir J. 2001 May;17(5):982-94
11488336
Proc Am Thorac Soc. 2007 Dec;4(8):602-5
18073390
Proteomics. 2006 Aug;6(15):4390-401
16819730
Glycobiology. 2007 Jul;17(7):698-712
17392389
Annu Rev Physiol. 2008;70:431-57
17850209
Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55
17507545
Biochem J. 1998 Sep 15;334 ( Pt 3):685-93
9729478
Biochem J. 1999 Mar 1;338 ( Pt 2):507-13
10024529
BMC Genomics. 2007 Aug 29;8:297
17727719
Am J Respir Cell Mol Biol. 2000 Nov;23(5):678-86
11062147
Histopathology. 2004 Nov;45(5):477-84
15500651
Thorax. 2006 Jan;61(1):86-8
16227325
Am J Respir Cell Mol Biol. 2004 Jul;31(1):86-91
14988081
Biochem J. 1996 Jan 15;313 ( Pt 2):431-9
8573075
Glycobiology. 1999 Mar;9(3):293-302
10024667
Hybrid Hybridomics. 2003 Oct;22(5):293-9
14678646
Am J Respir Cell Mol Biol. 2004 Feb;30(2):155-65
12882755
Exp Lung Res. 1985;9(3-4):289-308
4076055
Thorax. 2006 Nov;61(11):935-9
17071833