Cell- and stage-specific localization of galectin-3, a β-galactoside-binding lectin, in a mouse model of experimental autoimmune encephalomyelitis
Cell- and stage-specific localization of galectin-3, a β-galactoside-binding lectin, in a mouse model of experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.neuint.2018.06.007
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发表时间：
2018-09-01
影响因子：
4.2
通讯作者：
Nio-Kobayashi, Junko
中科院分区：
文献类型：
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作者：
Itabashi, Tetsuya;Arima, Yasunobu;Nio-Kobayashi, Junko
多发性硬化症（Multiple sclerosis， MS）是一种自身免疫性疾病，致病性T细胞在其中起着重要作用，实验性自身免疫性脑脊髓炎（EAE）被用作MS的动物模型。在15个半凝集素成员中，半凝集素-1、-8和-9在MS和EAE中发挥免疫抑制作用；然而，半乳糖凝集素-3 （gal-3）的作用是复杂和有争议的。我们检测了gal-3在EAE小鼠脊髓和神经根中的表达。在幼年小鼠中未检测到免疫组化信号，而在EAE小鼠的脊髓和神经根的下腰椎水平出现了gal-3。在脊髓中，gal-3阳性细胞被激活为小胶质细胞和/或浸润性巨噬细胞，巨噬细胞呈圆形，溶酶体酶组织蛋白酶D增强，表明吞噬活性升高。脊髓中gal -3阳性细胞在症状高峰期最为丰富。在恢复期，它们从脊髓实质中消失，但在脑膜中仍保持中等水平。有趣的是，gal-3阳性细胞选择性地出现在穿过椎管的神经根的腹侧，而不是背侧，在恢复期表达达到峰值。在腹侧神经根中，表达gal-3的主要细胞类型是围绕无髓鞘轴突并表达l-丝氨酸（一种有效的神经营养氨基酸）生物合成酶的特定雪旺细胞群。bal/ f4 /80阳性巨噬细胞也诱导了Gal-3，巨噬细胞吞噬受损的髓磷脂和轴突碎片。因此，gal-3在不同类型的细胞中被诱导，这些细胞参与了受损轴突和细胞碎片的清除以及轴突再生和髓鞘再生，这表明gal-3在EAE小鼠中具有潜在的神经保护作用。
Multiple sclerosis (MS) is an autoimmune disease in which pathogenic T cells play an important role, and an experimental autoimmune encephalomyelitis (EAE) is used as an animal model of MS. Galectins are beta-galactoside-binding lectins and involved in various physiological and pathological events. Among fifteen members of galectins, galectin-1,-8, and -9 play immunosuppressive roles in MS and EAE; however, the role of galectin-3 (gal-3) is complex and controversial. We examined expression of gal-3 in the spinal cord and nerve roots of EAE mice. No immunohistochemical signals were detected in naive mice, whereas gal-3 appeared at lower lumbar levels of the spinal cord and nerve roots in EAE mice. In the spinal cord, gal-3-positive cells were activated microglia and/or infiltrating macrophages, which were round in shape and intensified for the lysosomal enzyme, cathepsin D, indicating elevated phagocytic activity. Gal-3-positive cells in the spinal cord were most abundant during the peak symptomatic period. In the recovery period, they disappeared from the spinal parenchyma but remained at moderate levels in the pia mater. Interestingly, gal-3-positive cells selectively appeared in ventral, but not dorsal, nerve roots running through the spinal canal, with expression peaking during the recovery period. In ventral nerve roots, the major cell type expressing gal-3 was a specific population of Schwann cells that surround unmyelinated axons and express the biosynthetic enzyme for L-serine, a potent neurotrophic amino acid. Gal-3 was also induced in Ibal/F4/80-positive macrophages, which engulf damaged myelin and axon debris. Thus, gal-3 is induced in distinct cell types that are engaged in removal of damaged axons and cell debris and axon regeneration and remyelination, suggesting a potential neuroprotective role of gal-3 in EAE mice.