Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide.
Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide.
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DOI：
10.1016/s0021-9258(18)53940-5
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发表时间：
1993-01
期刊：
影响因子：
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通讯作者：
R. Lorsbach;W. Murphy;C. Lowenstein;S. Snyder;S. Russell
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文献类型：
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作者：
R. Lorsbach;W. Murphy;C. Lowenstein;S. Snyder;S. Russell
巨噬细胞可以被激活以杀死肿瘤细胞和各种微生物。结果表明，一氧化氮（NO），许多巨噬细胞的细胞毒性功能的介质，大大增加时，小鼠巨噬细胞系RAW 264.7的细胞与细菌脂多糖（LPS）和干扰素-γ（IFN-γ）的共刺激，与单独的LPS相比。这种增加导致细胞毒性增加。北方分析表明，NO的产生增加之前，显着增强的诱导型巨噬细胞NO合酶（mac-NOS），催化NO的合成的mRNA的表达。放线菌酮抑制诱导mac-NOS mRNA的IFN-γ和LPS，表明这种mRNA的表达需要从头蛋白质合成。mac-NOS mRNA的表达升高不是由于其稳定性的增加。相反，IFN-γ和LPS的组合诱导的mac-NOS基因的转录速率比单独用LPS刺激高得多。这些结果提供了一个解释，为什么引发和触发刺激，如IFN-γ和LPS，分别协同激活巨噬细胞，并可能适用于解释如何IFN-γ增强NO依赖的杀微生物活性，以及在巨噬细胞。
Macrophages can become activated to kill both tumor cells and a variety of microbes. Results here show that synthesis of nitric oxide (NO), a mediator of many macrophage cytotoxic functions, was greatly increased when cells of the mouse macrophage cell line RAW 264.7 were costimulated with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), compared to LPS alone. This increase paralleled increases in cytotoxicity. Northern analysis showed that increased production of NO was preceded by markedly enhanced expression of mRNA for the inducible form of macrophage NO synthase (mac-NOS), which catalyzes the synthesis of NO. Cycloheximide inhibited the induction of mac-NOS mRNA by IFN-gamma and LPS, indicating that expression of this mRNA required de novo protein synthesis. Elevated expression of mac-NOS mRNA was not due to an increase in its stability. Rather, the combination of IFN-gamma and LPS induced a much higher rate of transcription of the mac-NOS gene than did stimulation with LPS alone. These results provide one explanation of why priming and triggering stimuli, such as IFN-gamma and LPS, respectively, synergistically activate macrophages and may be applicable to explaining how IFN-gamma augments NO-dependent microbicidal activity in macrophages as well.