Breathing pattern response and epithelial labeling in ozone-induced airway injury in neutrophil-depleted rats

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.