Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, China.
Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
J Neuroinflammation. 2020 Feb 19;17(1):67. doi: 10.1186/s12974-020-1713-z.
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).
Female C57BL/6 mice were immunized with MOG 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.
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.
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.
ADAMTS13（一种具有血小板反应蛋白 1 型基序的解整合素和金属蛋白酶，成员 13）在防止微血管血栓形成和炎症中起着至关重要的作用。多发性硬化症（MS）患者的血浆中检测到 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）小鼠模型来确定 ADAMTS13 在 MS 疾病进展中的作用。
雌性 C57BL/6 小鼠用 MOG 肽免疫，然后在预防和治疗两种情况下用 ADAMTS13 或载体进行治疗。分析小鼠的临床缺陷、白质脱髓鞘和炎症细胞浸润情况。为了探索潜在的机制，测定了 VWF 的表达和血脊髓屏障（BSCB）。
EAE 小鼠的血浆 ADAMTS13 活性受到抑制。用 ADAMTS13 治疗的 EAE 小鼠表现出疾病进程改善、脱髓鞘减少以及 T 淋巴细胞、中性粒细胞和单核细胞浸润脊髓减少。一致地，ADAMTS13 治疗降低了 EAE 小鼠脊髓中的 VWF 水平并抑制了 BSCB 破裂。然而，EAE 小鼠的血液和脾脏中的白细胞不受 ADAMTS13 给药的影响。
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 可能是 MS 患者的一种潜在治疗策略。
