title: Participation of collagenase and elastase in LPS-induced airway hyperresponsiveness in guinea pigs.
abstract: Bacterial lipopolysaccharide (LPS) cause airway hyperreactivity in guinea pigs pretreated with metopirone. LPS inhalation resulted in an increase in airway muscarinic reactivity measured by intravenous acetylcholine injection 1-4 h after the inhalation of LPS. The increase of pulmonary capillary permeability was observed 1-24 h after the inhalation of LPS, whereas the increase of leukocytes in bronchoalveolar lavage fluid (BALF) was observed 2 and 24 h after the inhalation of LPS. Increased cells are mainly neutrophil, eosinophil, and macrophage. From the histopathological study, acute mucosal injury and loss of epithelial cilia were observed 1-24 h after the inhalation of LPS. In order to investigate the phlogistic substance in LPS-induced hyperreactivity, the roles of collagenase and elastase were investigated. The activities of both enzymes were elevated 2 h after the inhalation of LPS. The inhalation of collagenase and elastase caused bronchial hyperreactivity and increased pulmonary permeability. The combined administration of prednisolone (10 mg/kg/day) and cyclophosphamide (10 mg/kg/day) for five days decreased LPS-induced hyperreactivity, pulmonary capillary increase, collagenase and elastase activities, and the number of nucleated cells in BALF 2 h after the inhalation of LPS. These results indicate the participation of collagenase and elastase in the onset of LPS-induced airway hyperreactivity in guinea pigs.
authors.affiliation: Department of Pharmacology, Gifu Pharmaceutical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nagai
authors.forename: F
authors.initials: F
authors.lastname: Tsuji
authors.forename: T
authors.initials: T
authors.lastname: Shimazawa
authors.forename: S
authors.initials: S
authors.lastname: Goto
authors.forename: K
authors.initials: K
authors.lastname: Yoshitake
authors.forename: A
authors.initials: A
authors.lastname: Koda
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000402:Airway Obstruction / Q000139:chemically induced; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000201:enzymology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D006168:Guinea Pigs; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D003012:Microbial Collagenase / Q000502:physiology*; D010196:Pancreatic Elastase / Q000502:physiology*; D011239:Prednisolone / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors; D014132:Trachea / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D011976:Receptors, Muscarinic; D003520:Cyclophosphamide; D011239:Prednisolone; D013252:Steroid 11-beta-Hydroxylase; D010196:Pancreatic Elastase; D003012:Microbial Collagenase; D000109:Acetylcholine; D008797:Metyrapone