Orlikowski D, Chazaud B, Plonquet A, Poron F, Sharshar T, Maison P, Raphaël J-C, Gherardi R K, Créange A
Réseau de Neuroimmunologie du Nerf Périphérique (AP/HP), INSERM E0011, Université Paris 12 Val-de-Marne, France.
J Neuroimmunol. 2003 Jan;134(1-2):118-27. doi: 10.1016/s0165-5728(02)00393-4.
Infiltration of activated lymphocytes and monocytes is a key phenomenon in the pathogenesis of Guillain-Barré syndrome (GBS) and experimental autoimmune neuritis (EAN). To investigate the role of chemokines, we determined the blood and nerve tissue expression of monocyte chemoattractant protein 1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, and its receptor CCR2 in GBS and EAN. MCP-1 circulating levels (ng/ml) in GBS were increased at the time of progression, peaked at the time of plateau and normalized with recovery. MCP-1 circulating levels were the highest in the most disabled patients. The number of circulating CCR2 positive cells was lower in patients with GBS than in healthy subjects (p<0.004). In GBS, MCP-1 expression was observed in epineurial and endoneurial vessels, on infiltrating cells, Schwann cells and in the endoneurial extracellular matrix. Some CCR2 positive cells were observed in nerve biopsies of GBS patients. In EAN, a slight positivity for MCP-1 was observed in the sciatic nerve. There was no circulating CCR2 positive cells. However, at the time of plateau, a conspicuous infiltration of CCR2 positive cells was observed in the sciatic nerve that was no longer observed at the time of recovery. These results suggest that MCP-1 and CCR2 may participate to the recruitment of circulating mononuclear cells in nerve tissue in EAN and GBS.
活化淋巴细胞和单核细胞浸润是吉兰 - 巴雷综合征(GBS)和实验性自身免疫性神经炎(EAN)发病机制中的关键现象。为了研究趋化因子的作用,我们测定了单核细胞趋化蛋白1(MCP - 1)及其受体CCR2在GBS和EAN患者血液及神经组织中的表达,MCP - 1是单核细胞和活化淋巴细胞的主要趋化因子。GBS患者病情进展时MCP - 1循环水平(ng/ml)升高,在平台期达到峰值,恢复时恢复正常。最严重残疾患者的MCP - 1循环水平最高。GBS患者循环中CCR2阳性细胞数量低于健康受试者(p<0.004)。在GBS中,MCP - 1表达见于神经外膜和神经内膜血管、浸润细胞、施万细胞以及神经内膜细胞外基质。在GBS患者的神经活检中观察到一些CCR2阳性细胞。在EAN中,坐骨神经中观察到MCP - 1呈轻微阳性。未发现循环CCR2阳性细胞。然而,在平台期,坐骨神经中观察到CCR2阳性细胞显著浸润,恢复时不再观察到。这些结果表明,MCP - 1和CCR2可能参与EAN和GBS中循环单核细胞向神经组织的募集。