Experimental allergic encephalomyelitis is inhibited in transgenic mice expressing human C-reactive protein
Experimental allergic encephalomyelitis is inhibited in transgenic mice expressing human C-reactive protein
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DOI：
10.4049/jimmunol.168.11.5792
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发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
Barnum, SR
中科院分区：
文献类型：
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作者：
Szalai, AJ;Nataf, S;Barnum, SR
我们在这里使用转基因模型展示了人 C 反应蛋白 (CRP) 可保护 C57BL/6 小鼠免受实验性过敏性脑脊髓炎 (EAE)。与野生型雌性转基因动物相比，伴随活性 EAE 诱导期的人类 CRP 急性期反应的持续时间与疾病发作的延迟相关。在转基因雄性中，人类 CRP 表达高于雌性，与同性对照相比，EAE 被延迟，其严重程度也降低。此外，在雄性转基因中，CD3(+) T 细胞、CD11b(+) 单核细胞和巨噬细胞对脊髓的浸润很少或没有，有时可以完全预防 EAE。 CRP 转基因还能抵抗由野生型供体转移致脑炎 T 细胞被动诱导的 EAE。人 CRP 对培养的致脑炎细胞具有三种作用，可能有助于在体内观察到的保护作用：1) CRP 抑制致脑炎肽诱导的 T 细胞增殖； 2）CRP抑制炎症细胞因子（TNF-α、IFN-γ）和趋化因子（巨噬细胞炎症蛋白-1a、RANTES、单核细胞趋化蛋白-1）的产生； 3) CRP 增加 IL-10 的产生。所有这三种作用只有在高浓度的人 CRP 存在的情况下才能在体外实现。综合数据表明，在伴随 EAE 的炎症急性期，CRP 转基因小鼠中循环人 CRP 的高水平抑制了炎症细胞和/或 T 细胞的破坏作用，而炎症细胞和/或 T 细胞则支持 EAE 的发生和发展。
We show here using a transgenic model that human C-reactive protein (CRP) protects against experimental allergic encephalomyelitis (EAE) in C57BL/6 mice. In transgenic compared with wild-type females, the duration of the human CRP acute phase response that accompanies the inductive phase of active EAE correlates with a delay in disease onset. In transgenic males, which have higher human CRP expression than females do, EAE is delayed, and its severity is reduced relative to same-sex controls. Furthermore, in male transgenics, there is little or no infiltration of the spinal cord by CD3(+) T cells and CD11b(+) monocytes and macrophages, and EAE is sometimes prevented altogether. CRP transgenics also resist EAE induced passively by transfer of encephalitogenic T cells from wild-type donors. Human CRP has three effects on cultured encephalitogenic cells that could contribute to the protective effect observed in vivo: 1) CRP inhibits encephalitogenic peptide-induced proliferation of T cells; 2) CRP inhibits production of inflammatory cytokines (TNF-alpha, IFN-gamma) and chemokines (macrophage-inflammatory protein-la, RANTES, monocyte chemoattractant protein-1); and 3) CRP increases IL-10 production. All three of these actions are realized in vitro only in the presence of high concentrations of human CRP. The combined data suggest that during the acute phase of inflammation accompanying EAE, the high level of circulating human CRP that is achieved in CRP-transgenic mice inhibits the damaging action of inflammatory cells and/or T cells that otherwise support onset and development of EAE.