The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types
The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types
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DOI：
10.1080/08958370304454
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发表时间：
2003-01-01
影响因子：
2.1
通讯作者：
Stone, V
中科院分区：
文献类型：
--
作者：
Dick, CAJ;Brown, DM;Stone, V
PM10含有一种超细成分，通常来自燃烧过程。这种超细组分可能是与PM10水平短暂上升相关的呼吸系统疾病恶化和心肺疾病死亡增加的一个因素。通过使用四种不同的超细颗粒(碳黑、钴、镍和二氧化钛)，我们着手确定超细颗粒的属性(表面积、化学成分、颗粒数量或表面反应性)在体内和体外对其毒性和促炎作用贡献最大。125mug超细碳黑(UFCB)和超细钴(UFCo)颗粒在4h和18h后均可诱导中性粒细胞大量涌入。随着中性粒细胞的流入，肺泡灌洗液(BAL)中巨噬细胞炎性蛋白-2(MIP-2)(4h)和γ-谷氨酰转肽酶(18h)均升高。超细镍(UFNi)直到18h才能引起中性粒细胞内流明显增加。在此时间点，UFNi诱导的中性粒细胞的增加与UFCo和UFCB诱导的中性粒细胞增加相当。UFTi注入大鼠肺内后并未引起中性粒细胞显著增加。颗粒样品在4h观察到的MIP-2水平和在18h诱导的中性粒细胞内流与表面自由基产生的模式(通过质粒断裂实验测量)一致，即UFCo、UFCB和UFNi都能引起炎症标志物的显著增加，以及诱导超螺旋DNA的显著耗竭，表明羟基自由基的产生。通过抗氧化剂N-乙酰半胱氨酸(NAC)和谷胱甘肽单乙酯(GSHme)在体外阻断颗粒诱导的肺泡巨噬细胞释放肿瘤坏死因子-α(TNF-α)的能力，进一步加强了自由基和活性氧物种(ROS)在介导超微炎症中的作用。PM10中的超细颗粒物可能会通过氧化应激引起不利影响，这可能会对易感人群产生影响。易感个体，如慢性阻塞性肺病或哮喘患者，已经表现出预先存在的氧化应激，因此处于职业或环境颗粒物引起的进一步氧化应激的准备状态。
PM10 contains an ultrafine component, which is generally derived from combustion processes. This ultrafine fraction may be a factor in the increases in exacerbations of respiratory disease and deaths from cardiorespiratory causes associated with transient increases in levels of PM10. By using four different ultrafine particles (carbon black, cobalt, nickel, and titanium dioxide), we set out to determine the attributes of the ultrafine particle (surface area, chemical composition, particle number, or surface reactivity) that contribute most to its toxicity and proinflammatory effects both in vivo and in vitro. Instillation of 125 mug ultrafine carbon black (UFCB) and ultrafine cobalt (UFCo) particles induced a significant influx of neutrophils at both 4 and 18 h postinstillation. Accompanying the influx of neutrophils was an increase in macrophage inflammatory protein-2 (MIP-2) (at 4 h) and an increase in gamma-glutamyl transpeptidase (at 18 h) in bronchoalveolar lavage fluid (BAL). Ultrafine nickel (UFNi) did not induce a significant increase in neutrophil influx until 18 h postinstillation. The increase in neutrophils induced by UFNi at this timepoint was comparable to that induced by UFCo and UFCB. UFTi did not induce a significant increase in neutrophils following instillation into the rat lung. The levels of MIP-2 observed at 4 h and neutrophil influx at 18 h induced by the particle samples were consistent with the pattern of surface free radical generation (as measured by the plasmid scission assay) whereby UFCo, UFCB, and UFNi all cause significant increases in inflammatory markers, as well as inducing a significant depletion of supercoiled plasmid DNA, indicative of hydroxyl radical generation. A role for free radicals and reactive oxygen species (ROS) in mediating ultrafine inflammation is further strengthened by the ability of the antioxidants N-acetylcysteine (NAC) and glutathione monoethyl ester (GSHme) to block the particle induced release of tumour necrosis factor-alpha (TNF-alpha) from alveolar macrophages in vitro. The ultrafine particles in PM10 may cause adverse effects via oxidative stress, and this could have implications for susceptible individuals. Susceptible individuals, such as those with COPD or asthma, already exhibit preexisting oxidative stress and hence are in a primed state for further oxidative stress induced by occupational or environmental particles.