Role of neutrophil elastase in endotoxin-induced mucus hypersecretion in rat nasal epithelium

In the present study, hypertrophic and metaplastic changes of goblet cells were induced in rat nasal epithelium by intranasal instillation of endotoxi n or elastase. A significant increase in the amount of intraepithelial muco substance was observed after 24 hours during 3 days of instillation. The el astase-induced mucus production was not inhibited in neutrophil-depleted ra ts, but the endotoxin-induced change was significantly inhibited. Intranasa l instillation of the neutrophil elastase inhibitor ONO-5046 partially inhi bited the endotoxin-induced mucus production. Epithelial mucus secretion wa s evaluated by the temporary decrease in the amount of intraepithelial muco substance. The endotoxin-induced mucus secretion peaked 3 to 6 hours after intranasal instillation coinciding with the peak of the intraepithelial neu trophil infiltration. The elastase-induced mucus secretion peaked 1 to 3 ho urs after intranasal instillation; intraepithelial neutrophil infiltration was not induced by elastase. These results indicate that neutrophil elastas e is an important mediator of the intraepithelial mucus synthesis and secre tion induced by endotoxin.