Department of Anatomy, School of Medicine, Jeju National University, Jeju 690-756, South Korea.
Brain Res. 2012 May 9;1453:77-86. doi: 10.1016/j.brainres.2012.03.023. Epub 2012 Mar 16.
Arginase-1, a marker for M2 phenotype alternatively activated macrophages, inhibits inflammation and is associated with phagocytosis of cell debris and apoptotic cells. We analyzed the expression of arginase-1, a competitive enzyme of inducible nitric oxide synthase (iNOS), in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis (EAE). Western blot analysis showed that both arginase-1 and iNOS significantly increased in the spinal cords of rats at the peak stage of EAE compared with the expression level in control animals (p<0.05) and declined thereafter. Immunofluorescent staining demonstrated that increased expression of arginase-1 in EAE spinal cords was confirmed in macrophages as well as in some neurons and astrocytes that were constitutively positive for arginase-1 in normal spinal cords. A semiquantitative analysis by immunofluorescence showed that in EAE lesions, an increased level of arginase-1 immunoreactivity was matched with ED1-positive macrophages, which were also positive for activin A, a marker for the M2 phenotype. Taking all of these findings into consideration, we postulate that the increased level of arginase-1, which is partly from M2 macrophages, contributes to the modulation of neuroinflammation in EAE lesions, possibly through the reduction of nitric oxide in the lesion via competition with iNOS for the use of L-arginine.
精氨酸酶-1 是 M2 表型的替代激活巨噬细胞的标志物，可抑制炎症，并与细胞碎片和凋亡细胞的吞噬作用有关。我们分析了实验性自身免疫性脑脊髓炎（EAE）Lewis 大鼠脊髓中精氨酸酶-1（诱导型一氧化氮合酶（iNOS）的竞争性酶）的表达。Western blot 分析显示，EAE 大鼠脊髓中精氨酸酶-1和 iNOS 的表达均在 EAE 发病高峰期明显高于对照组（p<0.05），此后下降。免疫荧光染色证实，EAE 脊髓中精氨酸酶-1的表达增加在巨噬细胞以及一些神经元和星形胶质细胞中得到证实，在正常脊髓中这些细胞固有地表达精氨酸酶-1。免疫荧光的半定量分析显示，在 EAE 病变中，精氨酸酶-1免疫反应性的增加水平与 ED1 阳性的巨噬细胞相匹配，后者也对激活素 A 呈阳性，激活素 A 是 M2 表型的标志物。综合这些发现，我们推测，增加的精氨酸酶-1水平部分来自 M2 巨噬细胞，可能通过与 iNOS 竞争 L-精氨酸的使用来减少病变中的一氧化氮，从而调节 EAE 病变中的神经炎症。
