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Participation of collagenase and elastase in LPS-induced airway hyperresponsiveness in guinea pigs

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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 hypereactivity, 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 cyclephosphamide (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.

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Nagai, H., Tsuji, F., Shimazawa, T. et al. Participation of collagenase and elastase in LPS-induced airway hyperresponsiveness in guinea pigs. Inflammation 15, 317–330 (1991). https://doi.org/10.1007/BF00917316

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