In vivo imaging of reactive oxygen and nitrogen species in inflammation using the luminescent probe L-012
In vivo imaging of reactive oxygen and nitrogen species in inflammation using the luminescent probe L-012
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DOI：
10.1016/j.freeradbiomed.2009.06.013
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发表时间：
2009-09-15
影响因子：
7.4
通讯作者：
Carlsen, Harald
中科院分区：
文献类型：
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作者：
Kielland, Anders;Blom, Thomas;Carlsen, Harald
活性氧和活性氮 (ROS/RNS) 的产生是炎症反应的重要组成部分，但慢性炎症下 ROS/RNS 水平长期升高可能会导致疾病的发展。由于 ROS/RNS 的快速周转以及 ROS/RNS 探针的敏感性和特异性有限，监测活体动物中的 ROS/RNS 具有挑战性。我们探索了使用化学发光探针 L-012 对活体小鼠炎症期间 ROS/RNS 产生进行无创成像。诱导各种炎症条件，并用超灵敏 CCD 相机记录 L-012 依赖性发光。从与炎症相对应的身体不同区域观察到强烈的发光信号。通过施用 SOD 模拟 tempol、NADPH 氧化酶抑制剂夹竹桃麻素和一氧化氮合成抑制剂 L-NAME 来减少信号，这表明需要 ROS/RNS 的存在。此外，在 Ncf1 基因突变的小鼠中，L-012 信号被消除，该基因编码 NADPH 氧化酶复合物 2 中的一种蛋白质，该复合物在炎症过程中会产生 ROS/RNS。总之，L-012在小鼠体内分布良好，并在体内介导强烈的ROS/RNS依赖性发光信号，可用于监测活体炎症的发展和调节。 (C) 2009 Elsevier Inc. 保留所有权利。
Production of reactive oxygen and nitrogen species (ROS/RNS) is an important part of the inflammatory response, but prolonged elevated levels of ROS/RNS as under chronic inflammation can contribute to the development of disease. Monitoring ROS/RNS in living animals is challenging due to the rapid turnover of ROS/RNS and the limited sensitivity and specificity of ROS/RNS probes. We have explored the use of the chemiluminescent probe L-012 for noninvasive imaging of ROS/RNS production during inflammation in living mice. Various inflammatory conditions were induced, and L-012-dependent luminescence was recorded with an ultrasensitive CCD camera. Strong luminescent signals were observed from different regions of the body corresponding to inflammation. The signal was reduced by administration of the SOD mimetic tempol, the NADPH oxidase inhibitor apocynin, and the inhibitor of nitric oxide synthesis L-NAME, signifying the requirement for the presence of ROS/RNS. Additionally, the L-012 signal was abolished in mice with a mutation in the Ncf1 gene, encoding a protein in the NADPH oxidase complex 2, which generates ROS/RNS during inflammation. In conclusion, L-012 is well distributed in the mouse body and mediates a strong ROS/RNS-dependent luminescent signal in vivo and is useful for monitoring the development and regulation of inflammation in living organisms. (C) 2009 Elsevier Inc. All rights reserved.