Hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium induced by endotoxin

To elucidate the mechanisms of epithelial mucus hypersecretion in upper respiratory airway inflammation, we produced hypertrophic and metaplastic changes of goblet cells in rat nasal respiratory epithelium by intranasal instillation of endotoxin. Significant increase of hypertrophic goblet cells was induced in the septal epithelium transversely sectioned at the level of incisive papilla at 24 h after the intranasal instillation of 0.1 mg of endotoxin. This change was completed after 3 d of endotoxin instillations and recovered by normal epithelium 7 d after the last instillation. Total cell number and the number of basal and ciliated cells counted over 2 mm of basal lamina did not change; however, the number of goblet cells increased and that of nongranulated secretory cells decreased time-dependently after endotoxin instillations. Mitotic rates examined after a 6-h colchicine metaphase blockade were very low at any time point studied, and cell division did not play a major role in this process. These results indicate that endotoxin induces hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium rather than a hyperplastic change, and this metaplasia is produced by direct conversion of nongranulated secretory cells into the goblet cells. Histochemical examination of this epithelium revealed that most of the mucus produced by these goblet cells was sulfomucin. Intraperitoneal injection of antirat neutrophil antiserum or cyclophosphamide depleted circulating blood neutrophils. Endotoxin-induced changes of goblet cells were significantly inhibited in these neutrophil-depleted rats, and intranasal instillation of elastase also induced hypertrophic and metaplastic changes of goblet cells.