Expression of excitatory amino acid transporter-2 (EAAT-2) and glutamine synthetase (GS) in brain macrophages and microglia of SIVmac251-infected macaques
Expression of excitatory amino acid transporter-2 (EAAT-2) and glutamine synthetase (GS) in brain macrophages and microglia of SIVmac251-infected macaques
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DOI：
10.1046/j.1365-2990.2002.00426.x
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发表时间：
2002-10-01
影响因子：
5
通讯作者：
Gras, G
中科院分区：
文献类型：
--
作者：
Chrétien, F;Vallat-Decouvelaere, AV;Gras, G
谷氨酸的钠依赖性转运体（兴奋性氨基酸转运体，EAATs）清除大脑中的细胞外谷氨酸，并防止兴奋性毒性神经元损伤。谷氨酰胺合成酶（GS）通过产生神经营养性氨基酸谷氨酰胺为神经元提供代谢支持。最近已在体外的巨噬细胞和小胶质细胞以及体内的两种急性炎症模型中证实了EAAT和GS的表达。这一观察结果可能会改变我们目前对脑部炎症的理解，目前认为活化的小胶质细胞和脑巨噬细胞通过产生包括谷氨酸在内的多种神经毒素而成为主要的神经毒性细胞。这些细胞表达EAAT和GS将具有神经保护和神经营养特性，从而抵消小胶质细胞活化的有害后果。
猴免疫缺陷病毒（SIV）感染猕猴被认为是人类获得性免疫缺陷综合征（艾滋病）最相关的模型，包括在感染的早期无症状阶段出现脑部慢性炎症，随后出现类似艾滋病的疾病，此时会发生神经元死亡。我们研究了3只感染SIVmac251的食蟹猕猴和2只未感染的食蟹猕猴大脑中EAAT - 2和GS的表达。我们发现，在感染的灵长类动物中，小胶质细胞和脑巨噬细胞都表达EAAT - 2和GS，这表明这些细胞可能像星形胶质细胞一样，清除细胞外谷氨酸并为神经元提供谷氨酰胺。因此，小胶质细胞和巨噬细胞除了产生神经毒素外，还可能具有神经保护和神经营养特性。这一发现可能解释了早期强烈的小胶质细胞活化与晚期神经元凋亡细胞死亡发生之间的差异，神经元凋亡细胞死亡主要在疾病的终末期观察到。
Na+-dependent transporters for glutamate (excitatory amino acid transporters, EAATs) clear extracellular glutamate in the brain and prevent excitotoxic neuronal damage. Glutamine synthetase (GS) provides metabolic support for neurones by producing the neurotrophic amino acid glutamine. EAAT and GS expression has recently been demonstrated in macrophages and microglial cells in vitro , and in two models of acute inflammation in vivo . This observation might modify our current understanding of brain inflammation, which considers activated microglia and brain macrophages as the main neurotoxic cells through their production of a variety of neurotoxins, including glutamate. EAAT and GS expression by these cells would entail neuroprotective and neurotrophic properties, counterbalancing the deleterious consequences of microglial activation.Macaque infection by the simian immunodeficiency virus (SIV) is considered the most relevant model for human acquired immunodeficiency syndrome (AIDS), including chronic inflammation of the brain at the early asymptomatic stage of the infection, followed by an AIDS-like disease where neuronal death occurs. We studied the expression of EAAT-2 and GS in the brains of three SIVmac251-infected and two noninfected cynomolgus macaques. We found that both microglia and brain macrophages expressed EAAT-2 and GS in infected primates, suggesting that these cells might, like astrocytes, clear extracellular glutamate and provide glutamine to neurones. Microglia and macrophages could thus have neuroprotective and neurotrophic properties in addition to their production of neurotoxins. This finding might explain the contrast between early intense microglial activation and the late occurrence of neuronal apoptotic cell death, which is mainly observed at the terminal stage of the disease.