MUC5AC and a Glycosylated Variant of MUC5B Alter Mucin Composition in Children With Acute Asthma

作者:Welsh Kathryn G; Rousseau Karine; Fisher Gemma; Bonser Luke R; Bradding Peter; Brightling Chris E; Thornton David J; Gaillard Erol A*
来源:Chest, 2017, 152(4): 771-779.
DOI:10.1016/j.chest.2017.07.001

摘要

BACKGROUND: Diffuse airway mucus obstruction is an important feature of severe and fatal asthma. MUC5AC and MUC5B are the principal gel-forming mucins found in airway mucus. The mucin composition of airway mucus likely affects its functional properties. METHODS: We quantified the principal airway mucins MUC5AC and MUC5B in the sputum of age-matched children with acute and stable asthma and healthy control subjects by using Western blotting. RESULTS: Sputum samples from 38 children (13 with acute asthma, 15 with stable asthma, 10 control subjects) were obtained. Sputum MUC5AC concentrations were 7.6 mu g/mL in control subjects, 22.4 mu g/mL in those with stable asthma (P = .17), and 44.7 mu g/mL in those with acute asthma (P < .05). MUC5B concentrations showed less variation, with 238.5, 208.4 and 165.9 mu g/mL in control subjects, those with stable asthma, and those with acute asthma, respectively. The greater MUC5AC concentration in those with acute asthma resulted in a significantly altered MUC5B: MUC5AC ratio between control subjects and those with acute asthma (P < .05). Significant differences in MUC5B glycoforms were present between the groups, with the low-charge-only glycoform being found uniquely in those with acute asthma. CONCLUSIONS: Increased MUC5AC and the presence of a low-charge-only MUC5B glycoform significantly altered mucin composition in children with acute asthma. These changes may be important contributory factors to the airway mucus obstruction observed during acute asthma.

  • 出版日期2017-10