Effect of elastase instilled into the trachea on airways mechanics in guinea pigs

Abstract

Instilled elastase caused an inflammatory response in the lungs of guinea pigs which was observed at 6 h, 24 h, and 48 h post-treatment. The inflammation was most marked at 24 h and was characterised by a loss of epithelial cilia and detachment of epithelial cells from the basement membrane, a marked increase in polymorphonuclear leukocytes (PMNs) in blood vessels of the tracheal submucosa and an infiltration of macrophages into the parenchyma. Compared with controls, isolated tracheal preparations from 24 h and 48 h elastase pretreated animals were hyperreactive (Emax) to histamine and carbachol. This hyperreactivity persisted in tracheas from 48 h elastase pretreated animals after removal of the epithelial layer. Parenchymal strips were hyperreactive to histamine only. Tissue sensitivity (EC50) was little affected by elastase. Tracheal preparations incubated in 0.01% elastase for 3 h responded normally. In vivo responses of Raw and Cdyn to histamine were unaffected by elastase at 24 h and 48 h. However, the slope of the dose-response curve to acetylcholine was steepened 24 h after elastase instillation, but not at 48 h. In contrast to other models of inflammation elastase evokes in vitro but not in vivo hyperresponsiveness.