Regional differences in the response of the hamster airway epithelium to elastase: In vivo and In vitro studies
Alonso, Pedro A.
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The hamster model of experimental chronic bronchitis comprises a persistent increase in the proportion of bronchial granulated secretory cells after a single intratracheal instillation of elastase. This granulated secretory cell increase, which does not occur in the trachea, has been termed secretory cell metaplasia (SCM). Susceptibility of the bronchial epithelium may be due to a large population of elastase-responsive cells specific to this region. Three dimensional reconstruction of the major form of bronchial secretory cells revealed very little or no rough endoplasmic reticulum (RER), thus demonstrating significant regional heterogeneity since all epithelial secretory cells in the trachea have abundant RER. Animals with bronchial SCM were stimulated with pilocarpine to determine whether the cells subsequent to discharge would re-accumulate granules, thus indicating a permanent phenotypic change. However, bronchial secretory cells failed to discharge at doses equal to and greater than those claimed to be effective in rats. Elastase instilled intratracheally was immuno-localized in the hamster airways to assess the possibility of regional differences in cellular uptake of the enzyme. Elastase was not seen intracellularly in trachea or bronchus suggesting that initiation of bronchial SCM results from a cell surface effect, possibly because of elastase-specific sites on bronchial but not tracheal cells. Tracheal resistance was tested by challenging the epithelial cells in vivo and in vitro with very high doses of elastase. Light and electron microscopy revealed no evidence of a stimulation of the mucus synthetic apparatus, suggesting that tracheal epithelial cells are inherently resistant to proteolytic up-regulation.
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