SOURCES AND EFFECTS OF REACTIVE OXYGEN INTERMEDIATES IN THE BRAIN

细胞因子介导的诱导型一氧化氮合酶(INOS)激活 单核细胞或巨噬细胞因物种而异。与老鼠或 小鼠和人的巨噬细胞不能产生可测量的一氧化氮水平 (否)由炎性介质诱导。暴露于非细胞因子 然而，最近发现了肿瘤细胞或病毒等介体。 激活人类诱导型一氧化氮合酶。没有对这些调解人做出回应的生产 比大鼠或小鼠的细胞低得多，而且通常需要 几天的刺激。我们发现合成的，双倍的- 链状多核苷酸多肌苷-多胞苷(Poly I：C)， 通常用于模拟病毒暴露，激活人类单核细胞中的iNOS- 衍生巨噬细胞(MDM)。NO的产生，用亚硝酸盐来衡量 Poly I：C刺激24小时后检测到蓄积。 单链多聚核糖核酸Poly I，但不是Poly C，也 增加了NO产量。MDM提高了亚硝酸盐的产量 用伽马或α-干扰素或其他免疫物质启动(预处理) IL-4等介质被诱导型一氧化氮合酶抑制剂N-甲基-L还原。 精氨酸(L-MMMA)。用Poly I：C在人体内引发NO产生 巨噬细胞为研究两者之间的差异提供了有用的工具 常用的动物模型和人类细胞，并可能提供对 这些差异的病理生理学意义。

Cytokine-mediated activation of inducible nitric oxide synthase (iNOS) in monocytes or macrophages is species specific. In contrast to rat or mouse, human macrophages do not produce measurable levels of nitric oxide (NO) when induced by inflammatory mediators. Exposure to non-cytokine mediators such as tumor cells or viruses, however, has recently been shown to activate human iNOS. NO production in response to these mediators is much lower than that seen for rat or mouse cells and often requires several days of stimulation. We have found that the synthetic, double- stranded polyribonucleotide polyinosinic-polycytidilic acid (Poly I:C), commonly used to mimic viral exposure, activated iNOS in human monocyte- derived macrophages (MDM). The production of NO, measured by nitrite accumulation, was detected after 24 hours of stimulation with Poly I:C. The single-stranded polyribonucleotide Poly I, but not Poly C, also increased NO production. Nitrite production was enhanced when the MDM were primed (pretreated) with gamma- or alpha-interferon or other immune mediators such as IL-4 and was reduced by the iNOS inhibitor, N-methyl-L- arginine(L-MMMA). The use of Poly I:C to initiate NO production in human macrophages provides a useful tool to study the differences between the commonly used animal models and human cells and may provide insight into the pathophysiological significance of these differences.