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MUC5B Is the Major Mucin in the Gel Phase of Sputum in Chronic Obstructive Pulmonary Disease

¹ Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom; ² North West Lung Centre, University of South Manchester Hospital National Health Service Foundation Trust, Wythenshawe Hospital, Manchester, United Kingdom; ³ Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, Hvidovre, Denmark

Correspondence and requests for reprints should be addressed to Jørgen Vestbo, M.D., Dr. Med. Sci., North West Lung Centre University of South Manchester Hospital NHS Foundation Trust, Wythenshawe Hospital, M23 9LT, Manchester, U.K. E-mail: jorgen.vestbo{at}manchester.ac.uk

Rationale: 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.

Objectives: 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.

Measurements and Main 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 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 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.

Key Words: chronic obstructive pulmonary disease • mucus • mucin • pathophysiology

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Smoking is a major risk factor in the development of chronic obstructive pulmonary disease (COPD). Chronic hypersecretion of mucin is thought to contribute to the progression of disease. However, little is known about the mucin composition of mucus in COPD. What This Study Adds to the Field We show that MUC5AC was the predominant mucin in smokers without airflow obstruction, whereas MUC5B was more abundant from the patients with COPD. Furthermore, there was a shift towards smaller mucins in the COPD group.