LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor.
LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor.
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LP-BM5 病毒感染的小鼠产生针对 AMPA 受体的激活性自身抗体。
DOI：
10.1172/jci11500
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Basile,AS
中科院分区：
文献类型：
--
作者：
Koustova,E;Sei,Y;Fossom,L;Wei,ML;Usherwood,PN;Keele,NB;Rogawski,MA;Basile,AS
α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体的自身抗体可能导致慢性过度兴奋综合征和神经退行性变，但其起源尚不清楚。我们检查了感染 LP-BM5 鼠白血病病毒的小鼠，这些小鼠表现出兴奋性脑损伤和高丙种球蛋白血症，以确定 AMPA 受体抗体的存在。内源性 IgG 在感染小鼠的新皮质和尾状核/壳核中的神经元上积累，并与天然和重组 AMPA 受体亚基相互作用，其相对丰度如下：GluR3 ≥ GluR1 > GluR2 = GluR4（通过免疫沉淀法测定）。在放射性配体测定中，来自感染小鼠的 IgG 制剂特异性抑制 [3H]AMPA 与脑匀浆中受体的结合，这种活性在 IgG 制剂预吸附到固定化 LP-BM5 病毒后消失。当这些 IgG 应用于海马锥体神经元或受损的小脑颗粒神经元时也会诱发电流。这些电流可以使用几种 AMPA 受体拮抗剂中的任何一种来阻断。因此，病毒感染可以部分通过分子模拟产生抗 AMPA 受体抗体。这些抗体可能会改变神经元信号传导，并导致这些小鼠中观察到的神经变性，而使用 AMPA 受体拮抗剂可能会抑制这种作用。
Autoantibodies to α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors may contribute to chronic hyperexcitability syndromes and neurodegeneration, but their origin is unclear. We examined LP-BM5 murine leukemia virus–infected mice, which manifest excitotoxic brain lesions and hypergammaglobulinemia, for the presence of AMPA-receptor Ab’s. Endogenous IgG accumulated upon neurons in the neocortex and caudate/putamen of infected mice and interacted with native and recombinant AMPA-receptor subunits with the following relative abundance: GluR3 ≥ GluR1 > GluR2 = GluR4, as determined by immunoprecipitation. In a radioligand assay, IgG preparations from infected mice specifically inhibited [3H]AMPA binding to receptors in brain homogenates, an activity that was lost after preadsorbing the IgG preparation to immobilized LP-BM5 virus. These IgGs also evoked currents when applied to hippocampal pyramidal neurons or to damaged cerebellar granule neurons. These currents could be blocked using any of several AMPA receptor antagonists. Thus, anti–AMPA-receptor Ab’s can be produced as the result of a virus infection, in part through molecular mimicry. These Ab’s may alter neuronal signaling and contribute to the neurodegeneration observed in these mice, actions that may be curtailed by the use of AMPA-receptor antagonists.