Pulmonary inflammatory response to inhaled ultrafine particles is modified by age, ozone exposure, and bacterial toxin
Pulmonary inflammatory response to inhaled ultrafine particles is modified by age, ozone exposure, and bacterial toxin
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DOI：
10.1080/089583700750019585
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发表时间：
2000-01-01
影响因子：
2.1
通讯作者：
Oberdörster, G
中科院分区：
文献类型：
--
作者：
Elder, ACP;Gelein, R;Oberdörster, G
流行病学研究表明，环境颗粒物水平升高与老年人心肺疾病发病率之间存在关联。这些发现受到质疑，部分原因是粒子可能不会单独作用来引起这些效应。我们假设，与单独给药相比，碳质环境超细颗粒和臭氧可以共同作用，在肺部诱发更大的氧化应激和炎症，并且这些作用会在受损、老化的肺部中放大。使用了两种受损肺模型：内毒素引发模型和老年肺气肿模型（T-SK 小鼠）。将年轻（10周）和年老（22个月）雄性F344大鼠和雄性T-SK小鼠（14-17个月）单独或组合暴露于超细碳颗粒（计数中值直径25 nm，110 mug/m(3)）和臭氧（1 ppm）6小时。吸入低剂量内毒素（大鼠和小鼠肺泡沉积剂量分别为 70 和 7.5 单位）用于模拟呼吸道感染。暴露后 24 小时评估细胞和生化灌洗参数以及肺灌洗细胞的氧化剂释放。在两个物种和年龄组中都观察到炎症细胞流入肺泡腔：内毒素引发后吸入超细碳和臭氧的组合导致灌洗液中性粒细胞的最大增加。一般来说，灌洗炎症细胞中未刺激和刺激的活性氧 (ROS) 释放与中性粒细胞反应密切相关。通过方差分析 (ANOVA) 确定，碳颗粒具有显着影响，并且碳与臭氧之间存在一致的相互作用。然而，这种相互作用在年轻大鼠与老年大鼠和老年 T-SK 小鼠中的方向相反：碳和臭氧相互作用，导致年轻大鼠中 ROS 活性降低，而老年大鼠和老年 T-SK 小鼠中 ROS 活性增强，表明引发的肺部炎症细胞存在年龄依赖性功能差异。这些结果表明，短时间吸入超细碳质颗粒会引起明显的肺部炎症和氧化应激，这些炎症和氧化应激会因年龄、污染物和呼吸道受损而改变。
Epidemiological studies demonstrate associations between increasing levels of ambient particles and morbidity in the elderly with cardiopulmonary disease. Such findings have been challenged partly because particles may not act alone to cause these effects. We hypothesized that carbonaceous ambient ultrafine particles and ozone can act together to induce greater oxidative stress and inflammation in the lung than when administered alone and that these effects would be amplified in the compromised, aging lung. Two models of a compromised lung were used: endotoxin priming and old-age emphysema (T-SK mice). Young (10 wk) and old (22 mo) male F344 rats and male T-SK mice (14-17 mo) were exposed to ultrafine carbon particles (count median diameter 25 nm, 110 mug/m(3)) and to ozone (1 ppm) alone and in combination for 6 h. inhalation of low-dose endotoxin (70 and 7.5 units estimated alveolar deposited dose in rats and mice, respectively) was used to model respiratory-tract infection. Cellular and biochemical lavage parameters and oxidant release from lung lavage cells were assessed 24 h after exposure. Inflammatory cell influx into the alveolar space was observed for both species and age groups: The combination of inhaled ultrafine carbon and ozone after endotoxin priming resulted in the greatest increase in lavage-fluid neutrophils. In general, the unstimulated and stimulated release of reactive oxygen species (ROS) from lavage inflammatory cells correlated well with the neutrophil response. There were significant effects of carbon particles as well as a consistent interaction between carbon and ozone as determined by analysis of variance (ANOVA). However this interaction was in the opposite direction in young rats versus old rats and old T-SK mice: Carbon and ozone interacted such that ROS activity was depressed in young rats, whereas it was enhanced in old rats and old T-SK mice, indicating age-dependent functional differences in elicited pulmonary inflammatory cells. These results demonstrate that ultrafine carbonaceous particles inhaled for short periods of time can induce significant pulmonary inflammation and oxidative stress that are modified by age, copollutants, and a compromised respiratory tract.