Participation of collagenase and elastase in LPS-induced airway hyperresponsiveness in guinea pigs.
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.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Tsuji
F
F
Shimazawa
T
T
Goto
S
S
Yoshitake
K
K
Koda
A
A
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
D008070:Lipopolysaccharides; D011976:Receptors, Muscarinic; D003520:Cyclophosphamide; D011239:Prednisolone; D013252:Steroid 11-beta-Hydroxylase; D010196:Pancreatic Elastase; D003012:Microbial Collagenase; D000109:Acetylcholine; D008797:Metyrapone