Krishna M T, Madden J, Teran L M, Biscione G L, Lau L C, Withers N J, Sandström T, Mudway I, Kelly F J, Walls A, Frew A J, Holgate S T
University Medicine, Southampton General Hospital, University of Southampton, UK.
Eur Respir J. 1998 Jun;11(6):1294-300. doi: 10.1183/09031936.98.11061294.
Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.
在环境臭氧峰值水平下短期暴露会导致健康人体内中性粒细胞流入并损害肺功能。为了研究导致中性粒细胞募集的机制并检验T细胞在急性炎症反应中的作用，我们让12名健康人在两个不同时间段分别暴露于百万分之0.2（ppm）的臭氧和过滤空气中2小时，期间有间歇性休息和运动（分钟通气量 = 30 L×min⁻¹）。暴露结束6小时后进行纤维支气管镜检查。检测支气管肺泡灌洗（BAL）液中的总蛋白、类胰蛋白酶、组胺、髓过氧化物酶、白细胞介素（IL）-8和生长相关癌基因-α（Gro-α），并进行细胞总数和分类计数。对BAL细胞进行流式细胞术检测，以研究总T细胞、T细胞受体（αβ和γδ）、T细胞亚群（CD4⁺和CD8⁺细胞）以及活化的T细胞亚群（CD25⁺）。使用免疫组织化学方法，对支气管活检组织中的中性粒细胞、肥大细胞、总T细胞数量、T细胞亚群、CD25⁺ T细胞以及包括P选择素、E选择素、细胞间黏附分子（ICAM）-1和血管黏附分子（VCAM）-1在内的白细胞内皮黏附分子进行定量分析。9名受试者有配对样本。臭氧暴露后，BAL液中多形核中性粒细胞（PMN）比例（p = 0.07）和上皮细胞比例（p = 0.05）增加了两倍。同时，IL-8（p = 0.01）、Gro-α（p = 0.05）和总蛋白浓度（p = 0.058）也升高。两种趋化因子与BAL液中PMN比例之间存在显著正相关。臭氧暴露后，CD4/CD8比值（p = 0.05）以及活化的CD4⁺（p = 0.01）和CD8⁺ T细胞比例（p = 0.04）显著降低。然而，活检组织中所研究的任何炎症标志物均未显示出显著变化。健康人短期暴露于0.2 ppm臭氧后，暴露后6小时外周气道出现中性粒细胞流入，但近端气道未出现明显炎症反应。这种反应似乎至少部分由白细胞介素-8和生长相关癌基因-α介导。
