Pino M V, Stovall M Y, Levin J R, Devlin R B, Koren H S, Hyde D M
California Primate Research Center, School of Veterinary Medicine, University of California, Davis 95616.
Toxicol Appl Pharmacol. 1992 Jun;114(2):268-76. doi: 10.1016/0041-008x(92)90077-6.
To test the hypothesis that neutrophils contribute to acute, ozone-induced epithelial damage in the lung, rats were depleted of their circulating neutrophils by intraperitoneal injection of a rabbit anti-rat neutrophil serum (ANS) 12 hr prior to an 8-hr exposure to 1.0 ppm ozone. Additional rats were given an injection of normal rabbit serum (NRS) prior to ozone exposure. Exposures were followed by postexposure periods in filtered air for 0, 4, or 16 hr. Control rats were given either ANS or NRS and then exposed only to filtered air. Analysis of bronchoalveolar lavage fluid (BALF) from NRS-treated rats revealed a significant increase in total neutrophils above that of controls at the 4- and 16-hr postexposure times, with a peak increase at 4 hr postexposure. In contrast, there was almost total ablation of the BALF neutrophil response in the ANS-treated rats at all times. Ozone caused an increase in BALF protein, fibronectin, and interleukin-6 above those in controls in both the NRS- and ANS-treated rats, but the only significant difference between the two groups was a level of fibronectin in the neutrophil-depleted animals higher than that in the neutrophil-sufficient animals at the 0-hr postexposure time. Electron microscopic morphometry on lungs fixed by intravascular perfusion demonstrated no significant differences in the volume per surface area epithelial basal lamina (Vs) of necrotic and degenerating epithelial cells in central acini between the neutrophil-depleted and neutrophil-sufficient animals. From these results, we concluded that neutrophils do not play a detectable role in contributing to the early epithelial damage in the lung caused by an acute exposure to ozone.
为了验证中性粒细胞是否会导致肺部急性臭氧诱导的上皮损伤这一假说，在暴露于1.0 ppm臭氧8小时之前12小时，通过腹腔注射兔抗大鼠中性粒细胞血清（ANS）使大鼠循环中的中性粒细胞减少。另外一些大鼠在臭氧暴露前注射正常兔血清（NRS）。暴露后，将大鼠置于过滤空气中0、4或16小时。对照大鼠注射ANS或NRS，然后仅暴露于过滤空气中。对NRS处理的大鼠支气管肺泡灌洗液（BALF）的分析显示，在暴露后4小时和16小时，总中性粒细胞数量较对照组显著增加，在暴露后4小时达到峰值。相比之下，ANS处理的大鼠在所有时间点BALF中的中性粒细胞反应几乎完全消失。臭氧使NRS处理组和ANS处理组大鼠的BALF中蛋白质、纤连蛋白和白细胞介素-6水平高于对照组，但两组之间唯一显著的差异是在暴露后0小时，中性粒细胞减少的动物中纤连蛋白水平高于中性粒细胞充足的动物。通过血管内灌注固定的肺组织的电子显微镜形态计量学分析显示，中性粒细胞减少的动物和中性粒细胞充足的动物之间，中央腺泡中坏死和变性上皮细胞的每表面积上皮基底膜体积（Vs）没有显著差异。从这些结果中，我们得出结论，中性粒细胞在急性暴露于臭氧引起的肺部早期上皮损伤中没有可检测到的作用。
