No abstract

To test the hypothesis that lung sensory C fibers protect the small distal airways and alveoli from oxidant injury, we compared the effects of inhalation of ozone (1 ppm) or filtered air for 8 h on lung injury and lung inflammation in four groups of rats: (1) normal rats exposed to filtered air; (2) normal rats exposed to ozone; (3) rats treated as neonates with capsaicin (50 mg/kg, intraperitoneally) and subsequently exposed to filtered air; and (4) rats treated as neonates with capsaicin and subsequently exposed to ozone. All rats were allowed to recover in filtered air for 0, 4, 16, and 40 h before necropsy. Rats exposed to filtered air (Groups 1 and 3) showed normal airway and parenchyma structure. Normal untreated rats exposed to ozone showed a random distribution of mild, interstitial inflammatory changes and epithelial necrosis of bronchi and bronchiolar epithelium. However, rats treated with capsaicin and subsequently exposed to ozone demonstrated severe acute interstitial inflammation and epithelial coagulate necrosis in all airways, especially in small, peripheral airways and parenchyma; all of these changes were statistically significant. These findings support our hypothesis that lung sensory C fibers protect the distal airways from oxidant injury during acute ozone inhalation.

To assess the role of lung sensory C fibers during and after inhalation of 1 part/million ozone for 8 h, we compared breathing pattern responses and epithelial injury-inflammation-repair in rats depleted of C fibers by systemic administration of capsaicin as neonates and in vehicle-treated control animals. Capsaicin-treated rats did not develop ozone-induced rapid, shallow breathing. Capsaicin-treated rats showed more severe necrosis in the nasal cavity and greater inflammation throughout the respiratory tract than did control rats exposed to ozone. Incorporation of 5-bromo-2'-deoxyuridine (a marker of DNA synthesis associated with proliferation) into terminal bronchiolar epithelial cells was not significantly affected by capsaicin treatment in rats exposed to ozone. However, when normalized to the degree of epithelial necrosis present in each rat studied, there was less 5-bromo-2'-deoxyuridine labeling in the terminal bronchioles of capsaicin-treated rats. These observations suggest that the ozone-induced release of neuropeptides does not measurably contribute to airway inflammation but may play a role in modulating basal and reparative airway epithelial cell proliferation.

To test the hypothesis that neutrophils enhance the repair of ozone (O3)-injured airway epithelium, we investigated breathing pattern responses and airway epithelial injury and repair in rats depleted of neutrophils using rabbit antirat neutrophil serum (ANS) and control rats treated with normal rabbit serum (NRS). Thirty-seven Wistar rats were exposed to O3 (1 ppm) or filtered air (FA) for 8 h followed by 8 h in FA. O3-exposed NRS- and ANS-treated rats showed similar progressive decreases in tidal volume and increase in breathing frequency, with maximal changes occurring at 8 h of exposure, whereas FA-exposed rats showed no significant changes. O3-exposed ANS-treated rats showed more epithelial necrosis in the nasal cavity, bronchi, and distal airways than did O3-exposed NRS-treated rats. Incorporation of 5-bromo-2-deoxyuridine (BrdU), a measure of cellular proliferation, was assessed using an optical disector to count BrdU- labeled terminal bronchiolar epithelial cells. O3-exposed ANS-treated rats had significantly less BrdU- labeled epithelial cells than did O3-exposed NRS-treated rats. We conclude that neutrophils contribute to the repair process by enhancing the proliferation of O3-injured airway epithelial cells.