Role for Mucin-5AC in Upper and Lower Airway Pathogenesis in Mice.

Mucin-5AC (MUC5AC) is a major secreted mucin in pathogenic airways. To determine its role in mucus-related airway disorders, -deficient () and wild-type () mice were compared in bleomycin-induced pulmonary fibrosis, respiratory syncytial virus (RSV) disease, and ozone toxicity. Significantly greater inflammation and fibrosis by bleomycin were developed in lungs compared to lungs. More severe mucous cell metaplasia in fibrotic lungs coincided with bronchial , , and overexpression. Airway RSV replication was higher in than in during early infection. RSV-caused pulmonary epithelial death, bronchial smooth muscle thickening, and syncytia formation were more severe in compared to . Nasal septal damage and subepithelial mucoserous gland enrichment by RSV were greater in than in . Ozone exposure developed more severe nasal airway injury accompanying submucosal gland hyperplasia and pulmonary proliferation in than in . Ozone caused periodic acid-Schiff-positive secretion only in nasal airways. Lung E-cadherin level was relatively lower in than in basally and after bleomycin, RSV, and ozone exposure. Results indicate that MUC5AC is an essential mucosal component in acute phase airway injury protection. Subepithelial gland hyperplasia and adaptive increase of other epithelial mucins may compensate airway defense in mice.