视神经脊髓炎IgG刺激原代培养大鼠星形胶质细胞免疫反应

Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures

视神经脊髓炎(NMO)主要累及星形胶质细胞,导致中枢神经系统炎症、脱髓鞘和组织损伤。脑内病灶常高表达水通道蛋白4(AQP4),AQP4被认为是NMO血清IgG的抗原目标。根据NMO的可逆性及对NMO病灶演变特点的分析,笔者推测NMO IgG可能诱导了星形胶质细胞的动态免疫过程。培养原代大鼠星形胶质细胞,加入从NMO患者血清中提取或纯化的IgG,星形胶质细胞出现炎性增殖,同时基因表达出现与之匹配的明显变化。且星形胶质细胞反应因子脂质运载蛋白-2、多种趋化因子、细胞因子、应激反应因子的表达均增加。而在培养的原代星形胶质细胞中加入从正常对照者血清中提取的IgG则无上述变化。此星形胶质细胞的反应还与疾病种类相关。从复发缓解型多发硬化、Sj觟gren's或系统性红斑狼疮患者血清中提取的IgG加入培养的原代星形胶质细胞中也不能导致上述变化。笔者推测是NMO IgG与AQP4结合,导致星形胶质细胞出现炎症反应,并出现基因在转录和翻译水平的相应变化。抑制星形胶质细胞的炎症反应可能有助于减少星形胶质细胞增殖,缓解NMO病灶的发展。

Neuromyelitis optica （NMO） is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin-4 （AQP4） water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte-enriched cultures and treatment with NMO patient-derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin-2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease-specific, as serum from patients with relapsing-remitting multiple sclerosis, Sjogren＇s, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development.