Liu L, Leech J A, Urch R B, Poon R, Zimmerman B, Kubay J M, Silverman F S
Environmental Health Directorate, Health Canada, Ottawa, ON, Canada.
Inhal Toxicol. 1999 Aug;11(8):657-74. doi: 10.1080/089583799196790.
We examined ozone-induced upper and lower airway inflammatory responses and the concentrations of hydroxylated salicylate metabolites using nasal lavage fluid and induced sputum, in order to identify noninvasive and sensitive biomarkers for ozone exposure and effects. A time course for plasma concentration of 2, 3-dihydroxybenzoic acid (2,3-DHBA, a salicylate metabolite and an indicator for hydroxyl radical) in response to 0.12 ppm ozone was also studied. Healthy, young, nonsmoking volunteers were given acetylsalicylic acid (ASA, 975 mg) or placebo orally. Subjects were exposed to ozone (0.12 or 0.4 ppm) or filtered air in an environmental chamber for 2 h, while performing intermittent exercise. Blood was collected hourly over a 4-h period. After exposure, nasal lavage fluid was collected, and sputum was induced using hypertonic saline. Results show that in sputum the percentage of neutrophils was significantly higher after the subjects were exposed to 0.4 ppm ozone (p<.05) than after they were exposed to filtered air or 0.12 ppm ozone. The absolute number and the percentage of macrophages were significantly lower at 0.4 ppm ozone than for filtered air control or 0.12 ppm ozone. The percentage of lymphocytes in sputum was also significantly lower at 0.4 ppm ozone than for filtered air control or 0.12 ppm ozone. The sputum cellular responses to ozone were not significantly altered by ASA treatment. In nasal lavage, cell counts and differentials did not change significantly after exposure to ozone in comparison to filtered air control. The cellular data indicate an acute inflammation developed during ozone exposure in the lower respiratory tract. The concentrations of total protein and interleukin-8 and the activity of N-acetyl-beta-D-glucosaminidase (a lysosomal enzyme) in nasal lavage and sputum did not change significantly following exposure to ozone in comparison to filtered air control. Plasma 2,3-DHBA concentration increased significantly following exposure to 0.12 ppm ozone in an exposure-dependent temporal pattern. Salicylate metabolites in nasal lavage fluid and sputum did not increase significantly following exposure to ozone. There was a marked variation of 2,3-DHBA concentrations in airway fluids. Data suggest that plasma 2,3-DHBA is a sensitive marker indicating acute ozone exposure, even at an ozone concentration that causes minimal observable airway effects in healthy subjects.
我们使用鼻腔灌洗液和诱导痰检测了臭氧诱导的上、下呼吸道炎症反应以及羟基化水杨酸代谢物的浓度，以确定用于臭氧暴露及其影响的非侵入性且敏感的生物标志物。我们还研究了血浆中2,3 - 二羟基苯甲酸（2,3 - DHBA，一种水杨酸代谢物及羟基自由基的指标）对0.12 ppm臭氧响应的时间进程。健康、年轻、不吸烟的志愿者口服乙酰水杨酸（ASA，975 mg）或安慰剂。受试者在环境舱中暴露于臭氧（0.12或0.4 ppm）或过滤空气中2小时，同时进行间歇性运动。在4小时内每小时采集一次血液。暴露后，收集鼻腔灌洗液，并使用高渗盐水诱导痰液。结果显示，与暴露于过滤空气或0.12 ppm臭氧后相比，受试者暴露于0.4 ppm臭氧后痰液中中性粒细胞百分比显著更高（p<0.05）。在0.4 ppm臭氧浓度下，巨噬细胞的绝对数量和百分比显著低于过滤空气对照组或0.12 ppm臭氧浓度组。痰液中淋巴细胞百分比在0.4 ppm臭氧浓度下也显著低于过滤空气对照组或0.12 ppm臭氧浓度组。ASA治疗并未显著改变痰液对臭氧的细胞反应。在鼻腔灌洗中，与过滤空气对照组相比，暴露于臭氧后细胞计数和分类没有显著变化。细胞数据表明在臭氧暴露期间下呼吸道发生了急性炎症。与过滤空气对照组相比，暴露于臭氧后鼻腔灌洗液和痰液中总蛋白、白细胞介素 - 8的浓度以及N - 乙酰 - β - D - 氨基葡萄糖苷酶（一种溶酶体酶）的活性没有显著变化。血浆2,3 - DHBA浓度在暴露于0.12 ppm臭氧后以暴露依赖的时间模式显著增加。暴露于臭氧后鼻腔灌洗液和痰液中的水杨酸代谢物没有显著增加。气道液中2,3 - DHBA浓度存在明显差异。数据表明血浆2,3 - DHBA是指示急性臭氧暴露的敏感标志物，即使在健康受试者中引起最小可观察到的气道效应的臭氧浓度下也是如此。
