Coffey M J, Wheeler C S, Gross K B, Eschenbacher W L, Sporn P H, Peters-Golden M
Department of Internal Medicine, Taubman Center, University of Michigan, Ann Arbor, USA.
Toxicology. 1996 Dec 18;114(3):187-97. doi: 10.1016/s0300-483x(96)03487-7.
The environmental pollutant ozone, at sufficiently high levels, is known to induce pulmonary inflammation with resultant airway obstruction in normal subjects. Eicosanoids comprise one group of mediators released from alveolar macrophages which are involved in the pathogenesis of inflammatory lung diseases. We compared the effects of 2-h exposures to 0.4 ppm ozone and filtered air on pulmonary function and eicosanoid levels in bronchoalveolar lavage fluid in 11 normal healthy volunteers. Subjects were exposed to a 6-fold increase in minute ventilation using an adjusted work load on a cycle ergometer. All subjects complained of cough and dyspnea, and demonstrated increased airway obstruction, and increased specific airway resistance following ozone exposure as compared to air exposure. Bronchoalveolar lavage cell count demonstrated a 9-fold increase in the number of neutrophils with a lesser reduction in the number of alveolar macrophages following ozone exposure. Notably, bronchoalveolar lavage fluid leukotriene (LT) C4 (8-fold) and to a lesser extent LTB4 (1.5-fold) levels were higher following ozone exposure compared to air control, with no change in prostaglandins. In a subset of four subjects, alveolar macrophage arachidonic acid metabolism was studied in vitro following separate in vivo exposures to both ozone and air. Alveolar macrophages obtained following ozone exposure released more 5-lipoxygenase (1.5-fold) metabolites, with no change in cyclooxygenase metabolites, than did cells obtained following air exposure. These observations document activation of the 5-lipoxygenase pathway in the lung following ozone exposure, and suggest that alveolar macrophages may participate in the generation of LT, whose actions promote airway inflammation and obstruction.
已知环境污染物臭氧在足够高的浓度下会在正常受试者中诱发肺部炎症并导致气道阻塞。类花生酸是从肺泡巨噬细胞释放的一类介质，参与炎症性肺病的发病机制。我们比较了11名正常健康志愿者暴露于0.4 ppm臭氧和过滤空气2小时对肺功能和支气管肺泡灌洗液中类花生酸水平的影响。通过在自行车测力计上调整工作负荷，使受试者的分钟通气量增加6倍。与空气暴露相比，所有受试者在臭氧暴露后均出现咳嗽和呼吸困难，气道阻塞增加，比气道阻力增加。支气管肺泡灌洗细胞计数显示，臭氧暴露后中性粒细胞数量增加9倍，肺泡巨噬细胞数量减少较少。值得注意的是，与空气对照相比，臭氧暴露后支气管肺泡灌洗液中白三烯（LT）C4（8倍）以及程度较轻的LTB4（1.5倍）水平更高，前列腺素无变化。在一个由四名受试者组成的亚组中，分别在体内暴露于臭氧和空气后，对肺泡巨噬细胞花生四烯酸代谢进行了体外研究。与空气暴露后获得的细胞相比，臭氧暴露后获得的肺泡巨噬细胞释放出更多的5-脂氧合酶（1.5倍）代谢产物，环氧化酶代谢产物无变化。这些观察结果证明了臭氧暴露后肺中5-脂氧合酶途径的激活，并表明肺泡巨噬细胞可能参与LT的生成，其作用促进气道炎症和阻塞。
