COPD lungs show an attached stratified mucus layer resembling the protective colonic mucus

Abstract

The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) mucus accumulates due to goblet cell hyperplasia and mucin overexpression. To address mechanisms behind the mucus accumulation, the elastase-induced mouse model was utilized. The proteomes of bronchoalveolar lavage fluid from elastase-induced mice and COPD patients showed similarities to each other and to colonic mucus. Lung mucus showed a striated, laminated appearance in the elastase-induced mice, COPD and CF, resembling that observed for colonic mucus. Less mucus obstruction was observed in mice lacking the Muc5b mucin. The accumulated mucus plugs of the elastase-induced mice were possible to wash out, but a mucus layer covering the epithelium remained attached to the surface goblet cells also after hypertonic saline washings as widely used in CF therapy. The results suggest that the lung can convert its mucus system into an attached mucus layer that protects the epithelium, similarly to the colon.