Bassett D, Elbon-Copp C, Otterbein S, Barraclough-Mitchell H, Delorme M, Yang H
Department of Occupational and Environmental Health Sciences, Wayne State University, Detroit, Michigan 48202, USA.
J Toxicol Environ Health A. 2001 Dec 7;64(7):547-65. doi: 10.1080/15287390152627237.
Identifying whether or not neutrophils have a role to play in the early stages of acute lung epithelial injury brought about by inhalation of reactive substances continues to be a major area of investigation. In this study, the availability of circulating neutrophils was manipulated by treatment with either cyclophosphamide or rabbit antiserum against rat neutrophils, prior to exposures to air, a single high ozone exposure of 1 or 2 ppm for 3 h, or a continuous exposure to 0.8-1.0 ppm for up to 48 h. Although cyclophosphamide treatment resulted in undetectable levels of neutrophils in the blood, the recovery of tissue marginated-interstitial neutrophils of 1 x 10(6) cells by collagenase tissue digestion was not significantly diminished at the onset of air and ozone exposures. Cyclophosphamide treatment alone did not cause any permeability damage to air-exposed rat lungs, but did ameliorate ozone-induced increases in bronchoalveolar lavage (BAL) neutrophil and albumin recoveries after both short-term and 1 d of continuous ozone exposure. In contrast to cyclophosphamide, antiserum treatment resulted in greater than a 90% decrease in neutrophil recoveries from both blood and lung tissue at the onset of air and ozone exposures. Antiserum treatment also abrogated ozone-induced neutrophil accumulations in lung lavageable spaces following both single and continuous ozone exposures, but did not significantly affect ozone-associated lung permeability damage indicated by unaltered BAL fluid albumin recoveries. These data demonstrated that under experimental conditions when neutrophils remain within lung tissue marginated and interstitial pools, reduction in circulating blood neutrophil availability is associated with a concomitant decrease in ozone-induced lung damage.
确定中性粒细胞在吸入活性物质所致急性肺上皮损伤早期阶段是否发挥作用仍是一个主要研究领域。在本研究中，在暴露于空气、单次1或2 ppm高浓度臭氧3小时或持续暴露于0.8 - 1.0 ppm长达48小时之前，通过环磷酰胺或兔抗大鼠中性粒细胞抗血清处理来控制循环中性粒细胞的数量。尽管环磷酰胺处理导致血液中中性粒细胞水平检测不到，但在暴露于空气和臭氧开始时，通过胶原酶组织消化回收的1×10⁶个细胞的组织边缘 - 间质中性粒细胞并未显著减少。单独的环磷酰胺处理未对暴露于空气的大鼠肺造成任何通透性损伤，但在短期和持续1天的臭氧暴露后，确实改善了臭氧诱导的支气管肺泡灌洗（BAL）中性粒细胞和白蛋白回收率的增加。与环磷酰胺相反，抗血清处理导致在暴露于空气和臭氧开始时，血液和肺组织中的中性粒细胞回收率下降超过90%。抗血清处理还消除了单次和持续臭氧暴露后肺可灌洗空间中臭氧诱导的中性粒细胞积聚，但未显著影响由未改变的BAL液白蛋白回收率所表明的与臭氧相关的肺通透性损伤。这些数据表明，在实验条件下，当中性粒细胞保留在肺组织边缘和间质池中时，循环血液中中性粒细胞数量的减少与臭氧诱导的肺损伤的相应减少相关。
