Plopper C G, Chu F P, Haselton C J, Peake J, Wu J, Pinkerton K E
Department of Anatomy and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616.
Am J Pathol. 1994 Feb;144(2):404-20.
Two salient features of the pulmonary response to reactive oxidant air pollutants such as ozone are the heterogeneity of response by site within the respiratory tract and the development of tolerance to injury with repeated exposure. The purpose of this study was to establish whether the development of tolerance to long-term exposure is associated with changes in the tracheobronchial epithelium. Male F344-N rats were exposed to 0, 0.12, 0.5, or 1.0 ppm ozone 6 hours/day for 5 days/week for 20 months and killed 1 week post-exposure. Samples for light microscopic morphometry were obtained by microdissection from each infusion-fixed trachea and left lung lobe and included: 1) a cranial bronchus with short path length (generation no. 4 to 5) and small diameter; 2) a central bronchus with short path length (generation no. 4 to 5) and large diameter; and 3) a caudal bronchus with long path length (generation no. 10 to 12) and small diameter. In addition, three sites within the central acinus were examined from cranial, central, and caudal regions. These sites included terminal bronchiole, 0.5 to 1 mm proximal to terminal bronchiole and bronchiolarized alveolar duct. Intraepithelial mucin storage (AB/PAS-positive material quantified by image analysis) within the trachea decreased with dose. Mucin storage was unchanged in the central bronchus, increased threefold with dose in the caudal bronchus, and was six times higher in the cranial bronchus at 1.0 ppm ozone. Epithelial composition was unchanged in trachea or any bronchi; however, we noted a significant dose-dependent increase in nonciliated cell mass and volume fraction in terminal bronchioles in all three regions. There was also a significant increase in nonciliated cell mass in the bronchiolarized alveolar ducts. Bronchiolar nonciliated cells were identified greater than fourfold further into alveolar ducts in 1.0 ppm exposed than in 0 ppm animals. Nonciliated cells occurred almost 200 microns deeper into alveolar ducts in cranial regions than in caudal regions. We conclude: 1) that the development of tolerance to injury produced by long-term exposure to ozone involves changes in airway epithelium and 2) that these changes are site specific and involve alterations in both secretory activity and cellular composition.
肺部对活性氧化空气污染物（如臭氧）的反应有两个显著特征，即呼吸道内不同部位反应的异质性以及反复接触后对损伤产生耐受性。本研究的目的是确定长期接触后的耐受性发展是否与气管支气管上皮的变化有关。将雄性F344-N大鼠每天6小时、每周5天暴露于0、0.12、0.5或1.0 ppm的臭氧中，持续20个月，在暴露后1周处死。通过显微解剖从每个灌注固定的气管和左肺叶获取用于光镜形态测量的样本，包括：1）一条路径长度短（第4至5级）且直径小的头侧支气管；2）一条路径长度短（第4至5级）且直径大的中央支气管；3）一条路径长度长（第10至12级）且直径小的尾侧支气管。此外，从肺腺泡的头侧、中央和尾侧区域检查了三个部位。这些部位包括终末细支气管、终末细支气管近端0.5至1毫米处以及细支气管化的肺泡管。气管内的上皮黏液储存（通过图像分析量化的AB/PAS阳性物质）随剂量降低。中央支气管中的黏液储存没有变化，尾侧支气管中的黏液储存随剂量增加了三倍，在1.0 ppm臭氧浓度下，头侧支气管中的黏液储存是其六倍。气管或任何支气管中的上皮组成没有变化；然而，我们注意到所有三个区域的终末细支气管中，非纤毛细胞数量和体积分数有显著的剂量依赖性增加。细支气管化的肺泡管中的非纤毛细胞数量也有显著增加。与0 ppm动物相比，暴露于1.0 ppm的动物中，细支气管非纤毛细胞在肺泡管中的分布深入程度增加了四倍多。头侧区域的非纤毛细胞在肺泡管中的分布比尾侧区域深近200微米。我们得出结论：1）长期暴露于臭氧所产生的损伤耐受性发展涉及气道上皮的变化；2）这些变化具有部位特异性，涉及分泌活动和细胞组成的改变。
