BACKGROUND ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) plays a vital role in preventing microvascular thrombosis and inflammation. Reduced ADAMTS13 levels in plasma have been detected in multiple sclerosis (MS) patients. In the present study, we have determined the role of ADAMTS13 in the disease progression of MS using a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS Female C57BL/6 mice were immunized with MOG35-55 peptide and then treated with ADAMTS13 or vehicle in preventive and therapeutic settings. Mice were analyzed for clinical deficit, white matter demyelination and inflammatory cell infiltration. To explore the underlying mechanism, VWF expression and blood-spinal cord barriers (BSCB) were determined. RESULTS Plasma ADAMTS13 activity was suppressed in EAE mice. ADAMTS13-treated EAE mice exhibited an ameliorated disease course, reduced demyelination, and decreased T lymphocyte, neutrophil and monocyte infiltration into the spinal cord. Consistently, ADAMTS13 treatment reduced VWF levels and inhibited BSCB breakdown in the spinal cords of EAE mice. However, leukocytes in the blood and spleen of EAE mice remained unaffected by ADAMTS13 administration. CONCLUSION Our results demonstrate that ADAMTS13 treatment ameliorates inflammatory responses, demyelination and disease course in EAE mice. Therefore, our study suggests that ADAMTS13 may represent a potential therapeutic strategy for MS patients.

中文翻译：

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ADAMTS13改善了实验性自身免疫性脑脊髓炎的炎症反应。

背景技术ADAMTS13（具有血小板反应蛋白1型基序的整合素和金属蛋白酶，成员13）在预防微血管血栓形成和炎症中起着至关重要的作用。在多发性硬化症（MS）患者中，血浆中ADAMTS13水平降低。在本研究中，我们使用实验性自身免疫性脑脊髓炎（EAE）小鼠模型确定了ADAMTS13在MS疾病进展中的作用。方法用MOG35-55肽免疫雌性C57BL / 6小鼠，然后在预防和治疗环境中用ADAMTS13或媒介物治疗。分析小鼠的临床缺陷，白质脱髓鞘和炎性细胞浸润。为了探索潜在的机制，确定了VWF表达和血脊髓屏障（BSCB）。结果在EAE小鼠中血浆ADAMTS13活性被抑制。用ADAMTS13治疗的EAE小鼠的病程有所改善，脱髓鞘减少，T淋巴细胞，嗜中性粒细胞和单核细胞浸润到脊髓的数量减少。一致地，ADAMTS13治疗降低了EAE小鼠脊髓中的VWF水平并抑制了BSCB分解。但是，EAAM小鼠血液和脾脏中的白细胞仍然不受ADAMTS13给药的影响。结论我们的结果表明，ADAMTS13治疗可改善EAE小鼠的炎症反应，脱髓鞘和疾病进程。因此，我们的研究表明ADAMTS13可能代表MS患者的潜在治疗策略。ADAMTS13处理可降低EAE小鼠脊髓中的VWF水平并抑制BSCB分解。但是，EAAM小鼠血液和脾脏中的白细胞仍然不受ADAMTS13给药的影响。结论我们的结果表明，ADAMTS13治疗可改善EAE小鼠的炎症反应，脱髓鞘和疾病进程。因此，我们的研究表明ADAMTS13可能代表MS患者的潜在治疗策略。ADAMTS13处理可降低EAE小鼠脊髓中的VWF水平并抑制BSCB分解。但是，EAAM小鼠血液和脾脏中的白细胞仍然不受ADAMTS13给药的影响。结论我们的结果表明，ADAMTS13治疗可改善EAE小鼠的炎症反应，脱髓鞘和疾病进程。因此，我们的研究表明ADAMTS13可能代表MS患者的潜在治疗策略。