补体蛋白C3抑制轴突生长并促进神经元丢失。,Scientific Reports

当前位置： X-MOL 学术 › Sci. Rep. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

补体蛋白C3抑制轴突生长并促进神经元丢失。
Scientific Reports ( IF 3.8 ) Pub Date : 2017-Oct-10 , DOI: 10.1038/s41598-017-11410-x
Sheri L. Peterson , Hal X. Nguyen , Oscar A. Mendez , Aileen J. Anderson

对脊髓损伤（SCI）的炎症反应涉及先天性和适应性免疫细胞和蛋白质（包括补体级联反应）的定位和激活。补体C3对于补体激活的经典，替代和凝集素途径很重要，其裂解产物C3a和C3b在炎症的情况下介导多种功能，但对C3在受损神经元再生和存活中的潜在功能知之甚少在SCI之后。我们报告说，背侧半身切开并伴有周围条件损伤，C3 ^-/-小鼠与野生型C3 ^{+ / +}相比，脊髓中的感觉轴突再生增加了2倍老鼠。在体外，与单独的髓磷脂相比，C3的添加使髓磷脂介导的神经突增生抑制和神经元损失增加了两倍，而ELISA实验表明，髓磷脂丝氨酸蛋白酶裂解C3产生活性片段。向培养的神经元中添加纯化的C3裂解产物表明C3b负责C3的生长抑制以及神经毒性或抗粘附活性。这些数据表明，C3在体外可减少神经突向外生长和神经元活力，并在体内限制轴突再生，并证明该炎症蛋白在中枢神经系统中具有新颖的非传统作用。

"点击查看英文标题和摘要"

Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss.

The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage products C3a and C3b mediate several functions in the context of inflammation, but little is known about the potential functions of C3 on regeneration and survival of injured neurons after SCI. We report that 6 weeks after dorsal hemisection with peripheral conditioning lesion, C3^-/- mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord in comparison to wildtype C3^+/+ mice. In vitro, addition of C3 tripled both myelin-mediated neurite outgrowth inhibition and neuron loss versus myelin alone, and ELISA experiments revealed that myelin serine proteases cleave C3 to generate active fragments. Addition of purified C3 cleavage products to cultured neurons suggested that C3b is responsible for the growth inhibitory and neurotoxic or anti-adhesion activities of C3. These data indicate that C3 reduces neurite outgrowth and neuronal viability in vitro and restricts axon regeneration in vivo, and demonstrate a novel, non-traditional role for this inflammatory protein in the central nervous system.

更新日期：2017-10-10

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南