title: Lipopolysaccharide Induces Mucus Cell Metaplasia in Mouse Lung.
abstract: 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 aeruginosa LPS in mice resulted in massive recruitment of neutrophils to the lung 2 d after treatment as assessed by differential cell counts of the inflammatory cells in bronchoalveolar lavage fluid and histologic assessment of hematoxylin and eosin (H&E)-stained lung sections. The LPS-induced neutrophilic inflammation subsided substantially on Day 4 and essentially vanished by Day 7. Airway epithelial mucus cells were not detected by Alcian blue periodic acid-Schiff staining until Day 4 after LPS treatment and became more abundant 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 until Day 4 and peaked on Day 7. The expression of C2GnT-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-treated lung correlated with the presence of neutrophils and the appearance of mucus cells in the airway epithelium. We conclude that mucus cell metaplasia and hyperplasia can be generated in mouse lungs with a single intratracheal 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 hyperplasia model should be useful for the study of Pseudomonas-induced airway mucus hypersecretory diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology and the Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198-4525, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yanagihara
authors.forename: M
authors.initials: M
authors.lastname: Seki
authors.forename: P W
authors.initials: PW
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D001996:Bronchopneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D004396:Coloring Agents; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008679:Metaplasia / Q000139:chemically induced / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D004396:Coloring Agents; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger; D012965:Sodium Chloride; D017351:N-Acetylglucosaminyltransferases; C117361:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase