METABOLISM OF NITROXIDES BY LYMPHOCYTES AND MACROPHAGES

氮氧自由基是一种稳定的自由基，可被还原和再氧化 （代谢）由细胞和生物体。氮氧化物有可能 作为磁共振成像的造影剂， 可以实现，有必要了解影响因素 他们的新陈代谢。氧气的浓度是一个这样的因素;可能有 成为别人 这项提案的总体目标是研究氮氧化合物的代谢 在淋巴细胞和巨噬细胞中。这些细胞存在于循环系统中， 氮氧化合物最有可能被引入成像的系统 问题研究此外，淋巴细胞在免疫系统中发挥重要作用。 反应，并在刺激时发生剧烈的生理变化。这些 可以观察到氮氧化物代谢的变化。以这样 在一个案例中，氮氧化物将是“免疫反应”造影剂。 这里提出的工作将使用电子顺磁共振（EPR）， 研究氮氧代谢。将细胞保存在恒温水浴中 其中氧浓度和pH可以调节。这个浴缸里的细胞 将被泵入EPR光谱仪的空腔， 信号将被测量。可以添加氮氧化物和代谢抑制剂 直接进入浴槽中的细胞;细胞样品可以取出， 分析和可行性研究。 这项建议的具体目的是确定氮氧化物的比率 全血、分离的T和B淋巴细胞和巨噬细胞中的代谢， 和活化的淋巴细胞。氮氧化物的分子机制 将研究代谢以及所用氮氧化物的毒性 以及它们抑制淋巴细胞活化的浓度。 各种不带电的、部分或完全电离的氮氧化合物， 水溶性或脂溶性，并且具有不同的环结构 （哌啶、吡咯烷和恶唑烷）。此外，碳氢化合物 可能比其它脂溶性氮氧化物毒性小的氮氧化物 合成。

Nitroxides are stable free radicals which are reduced and reoxidized (metabolized) by cells and organisms. Nitroxides have the potential to act as contrast agents for magnetic resonance imaging but before this potential can be realized, it is necessary to understand the factors which affect their metabolism. The concentration of oxygen is one such factor; there may be others. The overall aim of this proposal is to study the metabolism of nitroxides in lymphocytes and macrophages. These cells are found in the circulatory system where nitroxides would most likely be introduced for imaging studies. In addition, lymphocytes play an important role in the immune response and undergo dramatic physiological changes upon stimulation. These changes may be observed as changes in the metabolism of nitroxides. In such a case, nitroxides would be 'immunologically responsive' contrast agents. The work proposed here will use electron paramagnetic resonance (EPR) to study nitroxide metabolism. Cells will be maintained in a thermostated bath in which oxygen concentration and pH can be regulated. Cells from this bath will be pumped into the cavity of the EPR spectrometer where the nitroxide signal will be measured. Nitroxides and metabolic inhibitors can be added directly to the cells in the bath; sample of cells can be withdrawn for analysis and viability studies. The specific aims of this proposal are to determine rates of nitroxide metabolism in whole blood, isolated T and B lymphocytes and macrophages, and activated lymphocytes. The molecular mechanisms involved in nitroxide metabolism will be studied as well as the toxicity of the nitroxides used and the concentrations at which they inhibit lymphocyte activation. A variety of nitroxides which are uncharged, partly, or completely ionized, water- or lipid-soluble, and which have different ring structures (piperidine, pyrrolidine, and oxazolidine) will be used. Also, hydrocarbon nitroxides which may be less toxic than other lipid-soluble nitroxides will be synthesized.