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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Barnes, P. J.. 1986. Neural control of human airways in health and disease.Am. Rev. Respir. Dis. 134:1289–1314.
Fabbri, L. M.. 1985. Airway inflammation and asthma.Prog. Biochem. Pharmacol. 20:18–25.
Nadel, J. A.. 1984. Inflammation and asthma.J. Allergy Clin. Immunol. 73:651–653.
Hulbert, W. M., T. McLean, andJ. C. Hogg. 1985. The effect of acute airway inflammation on bronchial reactivity in guinea pigs.Am. Rev. Respir. Dis. 132:7–11.
Chung, K. F., A. B. Becker, S. C. Lazarus, O. L. Frick, J. A. Nadel, andW. M. Guld. 1985. Antigen-induced airway hyperresponsiveness and pulmonary inflammation in allergic dogs.J. Appl. Physiol. 58:1347–1353.
Mue, S.. 1985. Bronchial hypersensitivity and bronchial asthma.Med. Immunol. 9:192–199 (in Japanese).
Hutchinson, A. A., J. M. Hinson, J. R. Kenneth, L. Brigham, andJ. R. Snapper. 1983. Effect of endotoxin on airway responsiveness to aerosol histamine in sheep.J. Appl. Physiol. 54:1463–1468.
Nagai, H., F.Tsuji, S.Goto, and A.Koda. A pharmacological study of LPS-induced airway hyperresponsiveness in guinea pigs (in preparation).
Rylander, R., B. Fogelmark, andM. Sjostrand. 1985. Free lung cell phagocytosis and lysosomal enzyme activity after inhalation of lipopolysaccharide in guinea pigs.Agents Actions 16:353–358.
Burrell, R., andR. Rylander. 1982. Further studies on inhaled endotoxin containing bacteria.Environ. Res. 27:325–336.
Rylander, R., L. Beijer, R. C. Lantz, R. Burrell, andP. Sedivy. 1988. Modulation of pulmonary inflammation after endotoxin inhalation with a platelet-activating factor antagonist (48740 RP).Int. Arch. Allergy Appl. Immunol. 86:303–307.
Burrell, R., R. C. Lantz, andD. E. Hinton. 1988. Mediators of pulmonary injury induced by inhalation of bacterial endotoxin.Am. Rev. Respir. Dis. 137:100–105.
Chung, K. F., H. Aizamm, G. D. Leikauf, I. F. Ueki, andJ. A. Nadel. 1985. Airway hyperresponsiveness induced by platelet activating factor: Role of thromboxane generation.J. Pharmacol. Exp. Ther. 236:580–584.
Swithenbank, J. M., D. S. Beer, D. Taylor, C. G. Abbot-Mcgreath. 1977. A larger diagnostic technique for measurement of droplet and particle size distribution.Prog. Astronaut. Aeronaut. 54:421–427.
Koda, A., H. Nagai, andT. Nishigaki. 1971. Pharmacological study of airway hyperreactivity.Jpn. J. Pharm. Suppl. 115:120.
Harris, E. D., Jr., andE. C. Cartwright. 1979. Collagenase.In “Proteinases in Mammalian Cells and Tissues. A. J. Barrett, editor. North-Holland Publishing, Amsterdam. 273–276.
Burleigh, M. C., A. J. Barrett, andG. S. Lazarus. 1974. Cathepsin B1, a lysosomal enzyme that degrades native collagen.Biochem. J. 137:387–398.
Starkey, P. M.. 1979. Elastase and cathepsin G, the serine proteinases of human neutrophil leukocytes and spleen.In Proteinases in Mammalian Cells and Tissues. A. J. Barrett, editor. North Holland Publishing, Amsterdam. 62–64.
Dunnett, C. W. 1964. New tables for multiple comparisons with control.Biometrics 50:482–489.
Mutoh, T., S. Koyama, O. Saitoh, M. Kanetaka, S. Dokuma, T. Horie, andD. Yasuoka. 1987. Time course of airway hyperresponsiveness and polymorphonuclear leukocyte counts in BALF following endotoxin inhalation.Jpn. J. Allergol. 36:101–107.
Hulbert, W. C., D. C. Walker, A. Jackson, andJ. C. Hogg. 1981. Airway permeability to horseradish peroxidase in guinea pigs: The repair phase after injury by cigarette smoke.Am. Rev. Respir. Dis. 123:320–326.
Wahl, L. M., S. W. Wahl, S. E. Mergenhagen, andG. R. Martin. 1974. Collagenase production by endotoxin-activated macrophages.Proc. Natl. Acad. Sci. U.S.A. 71:3598–3601.
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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
- Mucosal Injury
- Bronchoalveolar Lavage Fluid
- Airway Hyperresponsiveness
- Bacterial Lipopolysaccharide