TMEM119 and purinergic receptor P2Y12 (P2RY12), which are not expressed by recruited peripheral blood macrophages, are proposed to discriminate microglia from macrophages. Therefore, we investigated the distribution patterns of microglia and macrophages in 10 concentric lesions from four autopsied Baló's disease cases and one neuromyelitis optica spectrum disorder (NMOSD) case, using quantitative immunohistochemistry for the markers TMEM119, P2RY12, CD68, CD163 and GLUT5. Three cases with Baló's disease had distal oligodendrogliopathy (DO) showing preferential loss of myelin‐associated glycoprotein and early active demyelination in the outermost demyelinating layer (termed DMY‐MO). In DMY‐MO with DO, TMEM119‐positive activated microglia expressing upregulated GLUT5 but markedly downregulated P2RY12 were significantly increased. These activated microglia expressed inducible nitric oxide synthase. Oligodendrocytes and their precursors showed apoptotic‐like nuclear condensation in DMY‐MO. TMEM119‐negative and CD68/CD163‐positive macrophages were distributed throughout the lesion center of DMY‐MO with DO and these cells demonstrated foamy morphology only in the inner portion but not in the outer portion. In concentric demyelinating lesions from another Baló's case and lamellar demyelinating lesions in an NMOSD case, which had late active demyelination without DO, the densities of TMEM119‐, GLUT5‐ and P2RY12‐positive microglia with ramified morphology were significantly increased in myelinated layers but not in demyelinating layers. In particular, in the NMOSD case, TMEM119‐positive microglia were confined to the outer portion of the myelinated layers. CD68‐positive macrophages with foamy morphology also expressing CD163 accumulated in myelinated as well as in demyelinated layers. These findings suggest that activated microglia expressing TMEM119 and GLUT5, but not P2RY12, are associated with apoptosis of oligodendrocytes in the leading edge of Baló's concentric lesions with DO, whereas TMEM119‐, GLUT5‐ and P2RY12‐positive microglia with ramified morphology are associated with myelin preservation in concentric lesions without DO in Baló's disease and NMOSD. These two types of microglia appear to play distinct roles in the formation of concentric lesions.

中文翻译：

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Balo 病和视神经脊髓炎谱系疾病的同心圆和板层病变中不同的小胶质细胞和巨噬细胞分布模式。

TMEM119 和嘌呤能受体 P2Y12 (P2RY12) 不被募集的外周血巨噬细胞表达，被提议用于区分小胶质细胞和巨噬细胞。因此，我们使用定量免疫组织化学标记 TMEM119、P2RY12、CD68、CD163 和 GLUT5，研究了来自 4 例尸检 Balo 病病例和 1 例视神经脊髓炎谱系障碍 (NMOSD) 病例的 10 个同心病灶中小胶质细胞和巨噬细胞的分布模式。3 例 Balo 病患有远端少突胶质细胞病 (DO)，显示出髓鞘相关糖蛋白优先丢失和最外层脱髓鞘层（称为 DMY-MO）的早期活动性脱髓鞘。在具有 DO 的 DMY-MO 中，表达上调 GLUT5 但显着下调 P2RY12 的 TMEM119 阳性激活小胶质细胞显着增加。这些活化的小胶质细胞表达诱导型一氧化氮合酶。少突胶质细胞及其前体在 DMY-MO 中显示出类似凋亡的核凝聚。TMEM119 阴性和 CD68/CD163 阳性巨噬细胞分布在 DMY-MO 与 DO 的整个病变中心，这些细胞仅在内部表现出泡沫形态，而在外部没有。在另一个 Balo 病例的同心脱髓鞘病变和 NMOSD 病例的板层脱髓鞘病变中，在没有 DO 的情况下具有晚期活动性脱髓鞘，TMEM119-、GLUT5-和 P2RY12 阳性小胶质细胞的密度在有髓层中显着增加，但在脱髓鞘层。特别是，在 NMOSD 病例中，TMEM119 阳性小胶质细胞被限制在有髓层的外部。具有泡沫形态的 CD68 阳性巨噬细胞也表达在有髓鞘和脱髓鞘层中积累的 CD163。这些发现表明，表达 TMEM119 和 GLUT5 而非 P2RY12 的活化小胶质细胞与具有 DO 的 Balo 同心圆病变前缘少突胶质细胞的凋亡相关，而具有分叉形态的 TMEM119-、GLUT5-和 P2RY12 阳性小胶质细胞与髓鞘相关在 Balo 病和 NMOSD 中没有 DO 的同心病灶中的保留。这两种类型的小胶质细胞似乎在同心病灶的形成中发挥着不同的作用。与具有 DO 的 Balo 同心病灶前缘少突胶质细胞的凋亡相关，而具有分叉形态的 TMEM119、GLUT5 和 P2RY12 阳性小胶质细胞与 Balo 病和 NMOSD 中没有 DO 的同心病灶中的髓鞘保存有关。这两种类型的小胶质细胞似乎在同心病灶的形成中发挥着不同的作用。与具有 DO 的 Balo 同心病灶前缘少突胶质细胞的凋亡相关，而具有分叉形态的 TMEM119、GLUT5 和 P2RY12 阳性小胶质细胞与 Balo 病和 NMOSD 中没有 DO 的同心病灶中的髓鞘保存有关。这两种类型的小胶质细胞似乎在同心病灶的形成中发挥着不同的作用。