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

Chest. 2017 Oct;152(4):771-779. doi: 10.1016/j.chest.2017.07.001. Epub 2017 Jul 14.

Abstract

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 μg/mL in control subjects, 22.4 μg/mL in those with stable asthma (P = .17), and 44.7 μg/mL in those with acute asthma (P < .05). MUC5B concentrations showed less variation, with 238.5, 208.4 and 165.9 μg/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.

Keywords: airway obstruction; exacerbation; mucus; pediatric; sputum plug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Asthma / diagnosis
  • Asthma / metabolism*
  • Biomarkers / metabolism
  • Blotting, Western
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Mucin 5AC / metabolism*
  • Mucin-5B / metabolism*
  • Mucins / metabolism*
  • Mucus / metabolism*
  • Respiratory Mucosa / metabolism*
  • Sputum / chemistry*

Substances

  • Biomarkers
  • MUC5AC protein, human
  • MUC5B protein, human
  • Mucin 5AC
  • Mucin-5B
  • Mucins