Alveolar macrophage cytokine response to air pollution particles: Oxidant mechanisms
Alveolar macrophage cytokine response to air pollution particles: Oxidant mechanisms
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DOI：
10.1016/j.taap.2006.11.033
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发表时间：
2007-02-01
影响因子：
3.8
通讯作者：
Kobzik, Lester
中科院分区：
文献类型：
--
作者：
Imrich, Amy;Ning, YaoYu;Kobzik, Lester
用 LPS 引发并用浓缩环境空气颗粒 (CAP) 处理的肺泡巨噬细胞 (AM) 显示出肿瘤坏死因子 (TNF) 的释放增强，并为已有肺部疾病的人中观察到的空气污染颗粒的放大效应提供了体外模型。为了研究 CAP 在引发的大鼠 AM 中介导 TNF 释放的机制，我们首先测试了一组抗氧化剂的作用。 N-乙酰基-L-半胱氨酸 (20 mM)、二甲基硫脲 (20 mM) 和过氧化氢酶 (5 μM) 显着抑制与 CAP 一起孵育的引发 AM 的 TNF 释放。相反，当LPS引发的AM在外源氧化剂（葡萄糖氧化酶产生的H2O2，10μM/h）存在下用CAN处理时，TNF释放和细胞毒性显着增加。在外源 H2O2 存在的情况下，CAPs 悬浮液的可溶部分引起了大部分生物活性的增加。金属螯合剂去铁胺 (DFO) 强烈抑制可溶性部分与 H2O2 的相互作用，但对不溶性 CAPs 部分的生物活性没有影响。我们得出的结论是，CAP 可以通过至少两种不同的方式作用于氧化剂敏感的细胞因子释放来介导其在引发的 AM 中的作用。在引发的细胞中，PM 的不溶性成分介导 TNF 生成的增强，该生成依赖于 H2O2（过氧化氢酶敏感）但不依赖于铁（DFO 不敏感）。当 AM、PMN 或发炎的肺泡环境中的其他肺细胞释放外源性 H2O2 时，空气颗粒释放的可溶性铁也可以介导细胞因子释放和细胞毒性。 (c) 2006 Elsevier Inc. 保留所有权利。
Alveolar macrophages (AMs) primed with LPS and treated with concentrated ambient air particles (CAPs) showed enhanced release of tumor necrosis factor (TNF) and provide an in vitro model for the amplified effects of air pollution particles seen in people with preexisting lung disease. To investigate the mechanism(s) by which CAPs mediate TNF release in primed rat AMs, we first tested the effect of a panel of antioxidants. N-Acetyl-L-Cysteine (20 mM), dimethyl thiourea (20 mM) and catalase (5 mu M) significantly inhibited TNF release by primed AMs incubated with CAPs. Conversely, when LPS-primed AMs were treated with CAN in the presence of exogenous oxidants (H2O2 generated by glucose oxidase, 10 mu M/h), TNF release and cell toxicity was significantly increased. The soluble fraction of CAPs suspensions caused most of the increased bioactivity in the presence of exogenous H2O2. The metal chelator deferoxamine (DFO) strongly inhibited the interaction of the soluble fraction with H2O2 but had no effect on the bioactivity of the insoluble CAPs fraction. We conclude that CAPs can mediate their effects in primed AMs by acting on oxidant-sensitive cytokine release in at least two distinct ways. In the primed cell, insoluble components of PM mediate enhanced TNF production that is H2O2-dependent (catalase-sensitive) yet independent of iron (DFO-insensitive). In the presence of exogenous H2O2 released by AMs, PMNs, or other lung cells within an inflamed alveolar milieu, soluble iron released from air particles can also mediate cytokine release and cell toxicity. (c) 2006 Elsevier Inc. All rights reserved.