Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs

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), bacteria and mucus accumulates instead. To address the mechanisms behind the mucus accumulation, the proteome of bronchoalveolar lavages from COPD patients and mucus collected in an elastase-induced mouse model of COPD was analyzed, revealing similarities with each other and with the protein content in colonic mucus. Moreover, stratified laminated sheets of mucus were observed in airways from patients with CF and COPD and in elastase-exposed mice. On the other hand, the mucus accumulation in the elastase model was reduced in Muc5b-KO mice. While mucus plugs were removed from airways by washing with hypertonic saline in the elastase model, mucus remained adherent to epithelial cells. Bacteria were trapped on this mucus, whereas, in non-elastase-treated mice, bacteria were found on the epithelial cells. We propose that the adherence of mucus to epithelial cells observed in CF, COPD, and the elastase-induced mouse model of COPD separates bacteria from the surface cells and, thus, protects the respiratory epithelium.

Mucus and mucins in diseases of the intestinal and respiratory tracts

“…The mucus found in colon has a stratified appearance, also observed in the COPD and CF lungs as well as in older CF pigs and the elastase‐induced mouse model (Fig. ) . Furthermore, the colon mucus is characterized by its attachment to the goblet cells, something also observed in the elastase‐induced model.…”

“…Further studies of animals lacking either the MUC5B or MUC5AC mucin show that both these mouse strain can form an accumulated mucus layer and that this is dependent on both mucins . However, it seems as if the MUC5B mucin is more important at least in the mouse.…”

“…When bronchiolar lavage fluids from COPD patients were studied by proteomics methods, a number of proteins appeared that is typical for colon mucus . Furthermore, similar proteins are induced in a mouse model of chronic lung disease induced by elastase.…”

“…Only two inhalations of elastase in mice induced goblet cell hyperplasia and the accumulation of mucus causing clogged distal airways. The proteins found in both colon and disease lungs are FCGBP, CLCA1, TGM2, DBMT1 and the mucins MUC5AC and MUC5B .…”

“…This attached mucus cannot be removed by washing with PBS or hypertonic saline as used in the treatment of CF. Hypertonic saline removes most of the mucus plugging of the distal airways, but still leaves a thin mucus coat on the epithelium . The MUC2 mucin forms flat net‐like polymers that has the inherited tendency to form a stratified mucus .…”