SAP suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.

SAP suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.
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SAP 抑制 C57BL/6 小鼠实验性自身免疫性脑脊髓炎的发展

DOI:
10.1038/icb.2011.51
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发表时间:
2012-04
影响因子:
4
通讯作者:
Geng, Jian-Guo
Geng, Jian-Guo
中科院分区:
医学3区
文献类型:
--
作者:
Ji, Zhe;Ke, Zun-Ji;Geng, Jian-Guo

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实验性自身免疫性脑脊髓炎(EAE)是一种由CD4+T细胞介导的中枢神经系统疾病。血清淀粉样蛋白P组分(SAP)是一种高度保守的血浆蛋白,因其广泛存在于淀粉样蛋白沉积中而得名。在这里,我们报告了SAP转基因小鼠由于脑源性反应受损而意外地减弱了EAE。用髓鞘少突胶质细胞糖蛋白(MOG)肽35-55诱导CFA后,SAP转基因小鼠脊髓炎症减轻,EAE发作严重程度低于对照C57BL/6小鼠。然而,在SAP-KO小鼠中,EAE的严重性增强。将野生型抗原再刺激T细胞过继转移至SAP转基因小鼠,或将SAP转基因抗原再刺激T细胞转移至对照小鼠,可引起较轻微的EAE。MOG诱导的SAP转基因小鼠T细胞的增殖反应较弱。此外,在SAP转基因小鼠中,CD45阳性细胞在脊髓中几乎没有渗透。在体外,SAP抑制P-选择素刺激的IL-2的分泌,并阻断P-选择素与T细胞的结合。此外,SAP还可改变α4-整合素与T细胞的亲和力。提示SAP可能通过调节P-选择素的功能来拮抗EAE所致炎症急性期的发展。
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated disease of the CNS. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report SAP transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35–55 in CFA, SAP transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However in SAP-KO mice, the severity of EAE is enhanced. Adoptive transfer of Ag-restimulated T cells from wild-type to SAP transgenic mice or transfer of SAP transgenic Ag-restimulated T cells to control mice induced milder EAE. T cells from MOG-primed SAP transgenic mice showed weak proliferative responses. Furthermore, in SAP transgenic mice, there is little infiltration of CD45-positive cells in the spinal cord. In vitro, SAP suppressed the secretion of IL-2 stimulated by P-selectin, and blocked P-selectin binding to T cells. Moreover, SAP could change the affinity between α4-integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P-selectin.
缺乏实验性自身免疫性脑脊髓炎的胞质磷脂酶A2α缺陷型小鼠具有抗性。
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