Response of Rat Alveolar Macrophages to Ozone: Quantitative Assessment of Population Size, Morphology, and Proliferation following Acute Exposure

Abstract

The purpose of this study was to evaluate the in vivo effects of an acute exposure to low levels of ozone on rat pulmonary alveolar macrophages (PAM). Fisher 344 rats exposed to 0.0, 0.12, 0.8, or 1.5 ppm O₃ for 6 h were killed immediately after and 3, 18, 42, or 66h after ozone exposure and their lungs were lavaged. Compared to sham-exposed (control) rats, exposure to 0.12 ppm O₃ had no measurable effect on the total number, labeling index (LI), mitotic index (MI), or morphology of rat alveolar macrophages. The number of neutrophils was significantly (p ≤ 0.001) greater than in controls at 3, 18, and 42 h after exposure to 1.5 ppm O₃ and 42 h after exposure to 0.8 ppm O₃. The number of PAM was approximately twice that of controls 42 and 66 h after exposure to 0.8 and 1.5 ppm O₃. There was a significant (p ≤ 0.001) increase in PAM MI 42 and 66 h after exposure to 1.5 ppm O₃ and 42 h after 0.8 ppm O₃. The increase in the number of PAM in mitosis was preceded by an increase in PAM LI. The PAM LI was significantly (p ≤ 0.001) greater than controls 18 and 42 h after exposure but returned to near normal levels by 66 h after exposure. There was a transient decrease in the mean nuclear/cytoplasmic ratio of PAM from rats exposed to 1.5 ppm O₃ 18 and 42 h after exposure due to an increase in the mean PAM cytoplasmic area. Comparison of the PAM population doubling time (Dt) and cell cycle time (Ct) suggest that PAM proliferation played a significant role in the observed increase in PAM following exposure to 0.8 and 1.5 ppm O₃. These results highlight the dynamic response of PAM to an acute exposure to ozone and suggest that the proliferative response of pulmonary alveolar macrophages may be a useful indicator of pulmonary damage following inhalation of an irritant oxidant.