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首页> 外文期刊>American Journal of Physiology >Glutamate metabolism in HIV-infected macrophages: implications for the CNS.
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Glutamate metabolism in HIV-infected macrophages: implications for the CNS.

机译：艾滋病毒感染的巨噬细胞中的谷氨酸代谢：对中枢神经系统的影响。

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Central nervous system disorders are still a common complication of human immunodeficiency virus (HIV) infection and can lead to dementia and death. They are mostly the consequences of an inflammatory macrophagic activation and relate to glutamate-mediated excitotoxicity. However, recent studies also suggest neuroprotective aspects of macrophage activation through the expression of glutamate transporters and glutamine synthetase. We thus aimed to study whether HIV infection or activation of macrophages could modulate glutamate metabolism in these cells. We assessed the effect of HIV infection on glutamate transporter expression as well as on glutamate uptake by macrophages and showed that glutamate transport was partially decreased in the course of virus replication, whereas excitatory amino acid transporter-2 (EAAT-2) gene expression was dramatically increased. The consequences of HIV infection on glutamine synthetase were also measured and for the first time we show the functional expression of this key enzyme in macrophages. This expression was repressed during virus production. We then quantified EAAT-1 and EAAT-2 gene expression as well as glutamate uptake in differentially activated macrophages and show that the effects of HIV are not directly related to pro- or anti-inflammatory mediators. Finally, this study shows that glutamate transport by macrophages is less affected than what has been described in astrocytes. Macrophages may thus play a role in neuroprotection against glutamate in the infected brain, through their expression of both EAATs and glutamine synthetase. Because glutamate metabolism by activated macrophages is sensitive to both HIV infection and inflammation, it may thus be of potential interest as a therapeutic target in HIV encephalitis.
机译：中枢神经系统疾病仍然是人类免疫缺陷病毒（HIV）感染的常见并发症，并可能导致痴呆症和死亡。它们主要是炎症性巨噬细胞活化的结果，与谷氨酸介导的兴奋性毒性有关。但是，最近的研究也表明，通过谷氨酸转运蛋白和谷氨酰胺合成酶的表达，巨噬细胞激活的神经保护方面。因此，我们旨在研究HIV感染或巨噬细胞激活是否可以调节这些细胞中的谷氨酸代谢。我们评估了HIV感染对谷氨酸转运蛋白表达以及巨噬细胞对谷氨酸吸收的影响，结果表明，谷氨酸转运在病毒复制过程中部分降低，而兴奋性氨基酸转运蛋白2（EAAT-2）基因的表达却很明显增加。还测量了HIV感染对谷氨酰胺合成酶的影响，这是我们首次显示了该关键酶在巨噬细胞中的功能性表达。在病毒产生期间该表达被抑制。然后，我们对差异激活的巨噬细胞中EAAT-1和EAAT-2基因的表达以及谷氨酸的摄取进行了定量，结果表明HIV的影响与促炎或抗炎介质没有直接关系。最后，这项研究表明，与星形胶质细胞相比，巨噬细胞对谷氨酸的转运影响较小。因此，巨噬细胞通过其EAAT和谷氨酰胺合成酶的表达在神经保护谷氨酸中发挥作用。由于活化的巨噬细胞对谷氨酸的代谢对HIV感染和炎症都很敏感，因此作为HIV脑炎的治疗靶点可能引起人们的兴趣。

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