Bekircan-Kurt Can Ebru, Tan Ersin, Erdem Özdamar Sevim
Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Noro Psikiyatr Ars. 2015 Sep;52(3):279-282. doi: 10.5152/npa.2015.8801. Epub 2015 Jul 7.
The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor expressed in tissues and cells, which plays a role in immunity. The activation of RAGE results in the translocation of nuclear factor kappa B (NF-κB) to the nucleus for expression of proinflammatory molecules. The role of the RAGE pathway in the pathogenesis of diabetic complications is well determined. We aimed to investigate the role of the RAGE pathway in axonal and vasculitic neuropathy.
We immunoreacted nerve biopsy samples from 17 axonal neuropathy (AN), 11 vasculitic neuropathy (VN) and 12 hereditary neuropathy (as a control group) with liability to pressure palsy (HNPP) patients with antibodies to NF-κB and RAGE. Subsequently, we performed double staining with the antibodies to NF-κB or RAGE and T cells, macrophages and Schwann cells.
RAGE and NF-κB immunoreactivities were higher in the perivascular cuff and in endoneurial cells in VN than in AN and HNPP. Although there is no significant difference, nerve biopsies with AN showed higher NFκB and RAGE immunoreactivities than HNPP. The colocalization study showed that most of the NFκB- and RAGE-positive cells were CD8 (+) T cells in VN. In AN, all NFκB- and RAGE-positive cells were macrophages, whereas all NFκB- and RAGE-positive cells were Schwann cells in HNPP.
The activation of the RAGE pathway predominant in CD8 (+) T cells underscores its role in VN. In AN patients, the immunoreactivity to NFκB and RAGE in macrophages may support their role in axonal degeneration without inflammatory milieu.
晚期糖基化终末产物受体（RAGE）是一种在组织和细胞中表达的模式识别受体，在免疫中发挥作用。RAGE的激活导致核因子κB（NF-κB）易位至细胞核，以表达促炎分子。RAGE通路在糖尿病并发症发病机制中的作用已得到充分确定。我们旨在研究RAGE通路在轴索性和血管炎性神经病变中的作用。
我们用抗NF-κB和RAGE的抗体对17例轴索性神经病变（AN）、11例血管炎性神经病变（VN）患者以及12例遗传性神经病变（作为对照组，为有压迫性麻痹倾向的遗传性神经病变（HNPP）患者）的神经活检样本进行免疫反应。随后，我们用抗NF-κB或RAGE的抗体与T细胞、巨噬细胞和施万细胞进行双重染色。
与AN和HNPP相比，VN患者血管周围套袖和神经内膜细胞中的RAGE和NF-κB免疫反应性更高。虽然无显著差异，但AN患者的神经活检样本显示NFκB和RAGE免疫反应性高于HNPP。共定位研究表明，VN中大多数NFκB和RAGE阳性细胞为CD8（+）T细胞。在AN中，所有NFκB和RAGE阳性细胞均为巨噬细胞，而在HNPP中，所有NFκB和RAGE阳性细胞均为施万细胞。
CD8（+）T细胞中占主导的RAGE通路激活突出了其在VN中的作用。在AN患者中，巨噬细胞对NFκB和RAGE的免疫反应性可能支持它们在无炎症环境下轴索变性中的作用。
