Mucins in COPD MUC5B is the major mucin in the gel-phase of sputum in chronic obstructive pulmonary disease

Rationale: Overproduction of mucus is a contributory factor in the progression of 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 to smokers without airflow obstruction. Methods: The polymeric mucin composition of sputum from patients with COPD and smokers without airflow obstruction was analysed by western blotting analysis. The tissue localisation of the mucins was determined by immunohistochemistry, and their size distribution was analysed 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 COPD patients with a significant difference in the ratio of MUC5B:MUC5AC (p=0.004); this ratio was correlated with FEV1 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 gender, age and pack-year history. In both groups, MUC5AC was produced by surface epithelial cells and MUC5B by submucosal gland cells. Finally, there was a shift towards 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 on disease progression.