Rusznak C, Devalia J L, Sapsford R J, Davies R J
Dept of Asthma and Allergic Respiratory Diseases, St. Bartholomew's and the Royal London School of Medicine and Dentistry, The London Chest Hospital, UK.
Eur Respir J. 1996 Nov;9(11):2298-305. doi: 10.1183/09031936.96.09112298.
Although animal and human studies have demonstrated that ozone inhalation leads to airway epithelial inflammation and damage, the underlying mechanisms are not fully understood. We cultured human bronchial epithelial cells as explant cultures and investigated the effect of 6 h of exposure to 0-500 parts per billion (ppb) O3 with or without 10(-5) M nedocromil sodium on: 1) epithelial cell membrane integrity; and 2) release of inflammatory cytokines and soluble intercellular adhesion molecule-1 (sICAM-1), as assessed by enzyme-linked immunosorbent assay (ELISA). O3 exposure led to significant epithelial cell damage at concentrations of 10-500 ppb O3, as indicated by increased release of [51Cr]-labelled sodium chromate. At concentrations of 10-100 ppb, O3 induced maximal release of interleukin-8 (IL-8), granulocyte/macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and sICAM-1. The IL-8 and GM-CSF release increased significantly from 5.64+/-0.58 and 0.04+/-0.03 pg x microg(-1) cellular protein, respectively, from control cells exposed to air, to 20.16+/-2.56 and 0.20+/-0.04 pg x microg(-1) cellular protein, respectively, from cells exposed to 50 ppb O3. 10(-5) M nedocromil sodium significantly attenuated the O3-induced release of both IL-8 and GM-CSF (p<0.01). The TNF-alpha and sICAM-1 increases after exposure to 10-50 ppb O3, were also abrogated by treatment of the cells with 10(-5) M nedocromil sodium (p<0.05). Similarly, the antioxidant, glutathione, at concentrations of 400-600 microM, significantly reduced the O3-induced release of IL-8 (p<0.05). In conclusion, these studies indicate that ambient concentrations of ozone may induce airway inflammation, through release of proinflammatory mediators from airway epithelial cells. This effect may be inhibited both by the anti-inflammatory drug, nedocromil sodium, and the naturally occurring antioxidant glutathione.
尽管动物和人体研究表明，吸入臭氧会导致气道上皮炎症和损伤，但其潜在机制尚未完全明确。我们将人支气管上皮细胞培养成外植体培养物，并研究了暴露于0至500 ppb臭氧6小时，以及添加或不添加10(-5) M奈多罗米钠对以下两方面的影响：1）上皮细胞膜完整性；2）炎症细胞因子和可溶性细胞间粘附分子-1（sICAM-1）的释放，通过酶联免疫吸附测定（ELISA）进行评估。暴露于10至500 ppb臭氧浓度时，[51Cr]标记的铬酸钠释放增加，表明臭氧暴露导致了显著的上皮细胞损伤。在10至100 ppb浓度下，臭氧诱导白细胞介素-8（IL-8）、粒细胞/巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子-α（TNF-α）和sICAM-1的最大释放。IL-8和GM-CSF的释放分别从暴露于空气的对照细胞的5.64±0.58和0.04±0.03 pg x μg(-1)细胞蛋白，显著增加到暴露于50 ppb臭氧的细胞的20.16±2.56和0.20±0.04 pg x μg(-1)细胞蛋白。10(-5) M奈多罗米钠显著减弱了臭氧诱导的IL-8和GM-CSF释放（p<0.01）。用10(-5) M奈多罗米钠处理细胞后，暴露于10至50 ppb臭氧后TNF-α和sICAM-1的增加也被消除（p<0.05）。同样，浓度为400至600 μM的抗氧化剂谷胱甘肽显著降低了臭氧诱导的IL-8释放（p<0.05）。总之，这些研究表明，环境浓度的臭氧可能通过气道上皮细胞释放促炎介质诱导气道炎症。这种作用可能被抗炎药物奈多罗米钠和天然存在的抗氧化剂谷胱甘肽所抑制。
