Effect of inhaled endotoxin on intraepithelial mucosubstances in F344 rat nasal and tracheobronchial airways.

Increased sputum production and chronic bronchitis are associated with occupational exposure to endotoxin-contaminated organic ducts. The present study examined whether repeated exposure to occupationally relevant concentrations of airborne endotoxin in the F344 rat can alter the volume density of stored intraepithelial mucosubstances (Vs) in the respiratory tract. Rats were exposed to saline or endotoxin aerosols for 3 h/day for 3 days and were killed 24 h after the last exposure. Quantitative histochemistry of Vs in airway epithelium was examined at three distinct levels of the respiratory tract (nose, trachea, and lung). Exposure to endotoxin produced a dose-dependent increase in Vs in the intrapulmonary airways. The quantity of Vs in the intrapulmonary airways was significantly increased in animals exposed to as little as 0.3 micrograms/m3 endotoxin. Significant increases in Vs were observed in the trachea only after exposure to > or = 3.1 micrograms/m3 endotoxin, whereas no significant changes were observed in the nasal airways even at concentrations as high as 52.4 micrograms/m3. These results are consistent with earlier findings in which repeated instillation of endotoxin produced significant increases in Vs in the epithelial lining of the pulmonary airways and demonstrate that inhaled endotoxin may play a role in the increase in sputum and chronic bronchitis reported for workers exposed to organic dusts.