Lipopolysaccharide induces mucus cell metaplasia in mouse lung

A murine model of lipopolysaccharide (LPS)-induced airway inflammation and epithelial cell phenotypic change, and the time courses of these events are described. A single intratracheal instillation of Pseudomonas aeruginoso L PS in mice resulted in massive recruitment of neutrophils to the lung 2 d a fter treatment as assessed by differential cell counts of the inflammatory cells in bronchoalveolar lavage fluid and histologic assessment of hemotoxy lin and eosin (H&E)-stained lung sections. The LPS-induced neutrophilic inf lammation subsided substantially on Day 4 and essentially vanished by Day 7 . Airway epithelial mucus cells were not detected by Alcian blue periodic a cid-Schiff staining until Day 4 after LPS treatment and became more abundan t in number as well as in mucus content on Day 7. The expression of Muc5ac messenger RNA (mRNA) as well as glycoprotein was enhanced on Day 2, peaked on Day 4 and decreased on Day 7,whereas enhanced expression of mucin core 2 beta6 N-acetylglucosaminyltransferase (C2GnT)-M mRNA was not detected unti l Day 4 and peaked on Day 7. The expression of C2CnT-L mRNA in the lung, a marker for activated leukocytes as well as mucus cells, peaked on Day 2 and remained moderately high until Day 7. C2GnT-L mRNA expression in LPS-treat ed lung correlated with the presence of neutrophils and the appearance of m ucus cells in the airway epithelium. We conclude that mucus cell metaplasia and hyperplasia can be generated in mouse lungs with a single intratrachea l instillation of LPS. In addition, C2GnT-M may serve as a marker for mucus cells in mouse lung. This LPS-induced mucus cell metaplasia and hyperplasi a model should be useful for the study of Pseudomonos-induced airway mucus hypersecretory diseases.