Hotchkiss J A, Harkema J R, Kirkpatrick D T, Henderson R F
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Exp Lung Res. 1989;15(1):1-16. doi: 10.3109/01902148909069605.
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 66 h 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 less than or equal to 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 less than or equal to 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 less than or equal to 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.
本研究的目的是评估急性暴露于低水平臭氧对大鼠肺泡巨噬细胞（PAM）的体内影响。将Fisher 344大鼠暴露于0.0、0.12、0.8或1.5 ppm的臭氧中6小时，在暴露后立即以及暴露后3、18、42或66小时处死大鼠，并对其肺部进行灌洗。与假暴露（对照）大鼠相比，暴露于0.12 ppm的臭氧对大鼠肺泡巨噬细胞的总数、标记指数（LI）、有丝分裂指数（MI）或形态没有可测量的影响。暴露于1.5 ppm臭氧后3、18和42小时以及暴露于0.8 ppm臭氧后42小时，中性粒细胞数量显著（p小于或等于0.001）高于对照组。暴露于0.8和1.5 ppm臭氧后42和66小时，PAM数量约为对照组的两倍。暴露于1.5 ppm臭氧后42和66小时以及暴露于0.8 ppm臭氧后42小时，PAM的MI显著（p小于或等于0.001）增加。有丝分裂的PAM数量增加之前，PAM的LI增加。暴露后18和42小时，PAM的LI显著（p小于或等于0.001）高于对照组，但在暴露后66小时恢复到接近正常水平。由于PAM平均细胞质面积增加，暴露于1.5 ppm臭氧的大鼠在暴露后18和42小时，PAM的平均核/质比出现短暂下降。对PAM群体倍增时间（Dt）和细胞周期时间（Ct）的比较表明，PAM增殖在暴露于0.8和1.5 ppm臭氧后观察到的PAM增加中起重要作用。这些结果突出了PAM对急性臭氧暴露的动态反应，并表明肺泡巨噬细胞的增殖反应可能是吸入刺激性氧化剂后肺损伤的一个有用指标。
