Comparison of acute ozone-induced nasal and pulmonary inflammatory responses in rats

Abstract

The centriacinar pulmonary lesion induced by ozone has been extensively characterized, but little is known about the effects of this oxidant gas in the upper airways. The present study was designed to compare the effects of acute ozone exposure in the nose and lungs of rats. We examined the cellular inflammatory responses in the nasal cavity and lower respiratory tract by means of nasal and bronchoalveolar lavage and morphometric quantitation of neutrophils within the nasal mucosa and pulmonary terminal bronchioloalveolar duct regions (i.e., centriacinar). Rats were exposed to 0.0, 0.12, 0.8, or 1.5 ppm ozone for 6 hr and were sacrificed immediately or 3, 18, 42, or 66 hr following exposure. Eighteen hours after exposure, increased numbers of neutrophils, as compared to controls, were recovered from nasal lavage fluid (NLF) of rats exposed to 0.12 ppm ozone. There was no change in the number of neutrophils recovered from bronchoalveolar lavage fluid (BALF) at any time after exposure. Rats exposed to 0.8 ppm ozone had more neutrophils in NLF than controls immediately after exposure, but no concomitant increase in BALF neutrophils at that time. However, as the number of neutrophils in BALF increased (maximum at 42 hr), the number of neutrophils recovered from NLF decreased (minimum at 42 hr). Rats exposed to 1.5 ppm ozone had no significant increases in nasal neutrophils in NLF at any time after exposure but had greatly increased numbers of neutrophils in BALF 3, 18, and 42 hr after exposure. The number of neutrophils recovered by nasal and bronchoalveolar lavage accurately reflected the tissue neutrophil response at sites within the nasal cavity and lung that were injured by acute ozone exposure. Our results suggest that at high ozone concentrations (0.8 and 1.5 ppm), the acute nasal inflammatory response is attenuated by a simultaneous, competing, inflammatory response within the centriacinar region of the lung. Analysis of nasal lavage fluid for changes in cellular composition may be a useful indicator of acute exposure to ambient levels of ozone, but at higher ozone levels, the nasal cellular inflammatory response may underestimate the effects of ozone on nasal and pulmonary epithelia.