Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation.
Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation.
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DOI：
10.3389/fncel.2014.00374
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发表时间：
2014
影响因子：
5.3
通讯作者：
Sanchez D
中科院分区：
文献类型：
--
作者：
García-Mateo N;Ganfornina MD;Montero O;Gijón MA;Murphy RC;Sanchez D
脂质的管理，特别是控制神经炎症的信号脂质，对于受损神经系统的再生能力至关重要。对神经系统损伤后的促炎和抗炎信号的了解非常广泛，其中大多数是通过众所周知的受体和细胞内级联反应发挥作用的蛋白质。然而，脂质结合细胞外蛋白能够改变损伤后释放的脂质的命运的作用尚不清楚。载脂蛋白 D (ApoD) 是脂质运载蛋白家族的一种细胞外脂质结合蛋白，在神经系统损伤时诱导产生。我们之前的研究表明，如果没有 ApoD，轴突再生会延迟，并表明它参与了华勒变性期间的早期事件。在这里，我们证明 ApoD 由有髓鞘和非髓鞘雪旺细胞表达，并在神经损伤早期被诱导。我们发现，已知可结合花生四烯酸 (AA) 的 ApoD 在体外也可与溶血磷脂酰胆碱 (LPC) 相互作用。我们使用神经挤压损伤的体内模型、神经外植体损伤模型和暴露于纯化髓磷脂的培养巨噬细胞来揭示：（i）ApoD 调节去神经化的雪旺细胞巨噬细胞信号传导，抑制损伤时 MCP1 和 Tnf 依赖性巨噬细胞的募集和激活； (ii) ApoD 通过浸润的巨噬细胞控制吞噬激活剂 Galectin-3 的过度表达； (iii) ApoD 控制 LPC 和 AA 的基础水平和损伤触发水平； (iv) ApoD 改变髓磷脂-巨噬细胞相互作用的动力学，有利于吞噬作用的启动并促进髓磷脂降解。因此，雪旺源性 ApoD 对巨噬细胞行为的调节是调节神经损伤消退的关键机制。这些结果将 ApoD 作为一种脂质结合蛋白，在损伤后的神经恢复过程中控制神经胶质细胞、神经元和血源性细胞之间的信号交换，并为 ApoD 作为再生促进剂的治疗用途提供了可能性。
Management of lipids, particularly signaling lipids that control neuroinflammation, is crucial for the regeneration capability of a damaged nervous system. Knowledge of pro- and anti-inflammatory signals after nervous system injury is extensive, most of them being proteins acting through well-known receptors and intracellular cascades. However, the role of lipid binding extracellular proteins able to modify the fate of lipids released after injury is not well understood. Apolipoprotein D (ApoD) is an extracellular lipid binding protein of the Lipocalin family induced upon nervous system injury. Our previous study shows that axon regeneration is delayed without ApoD, and suggests its participation in early events during Wallerian degeneration. Here we demonstrate that ApoD is expressed by myelinating and non-myelinating Schwann cells and is induced early upon nerve injury. We show that ApoD, known to bind arachidonic acid (AA), also interacts with lysophosphatidylcholine (LPC) in vitro. We use an in vivo model of nerve crush injury, a nerve explant injury model, and cultured macrophages exposed to purified myelin, to uncover that: (i) ApoD regulates denervated Schwann cell-macrophage signaling, dampening MCP1- and Tnf-dependent macrophage recruitment and activation upon injury; (ii) ApoD controls the over-expression of the phagocytosis activator Galectin-3 by infiltrated macrophages; (iii) ApoD controls the basal and injury-triggered levels of LPC and AA; (iv) ApoD modifies the dynamics of myelin-macrophage interaction, favoring the initiation of phagocytosis and promoting myelin degradation. Regulation of macrophage behavior by Schwann-derived ApoD is therefore a key mechanism conditioning nerve injury resolution. These results place ApoD as a lipid binding protein controlling the signals exchanged between glia, neurons and blood-borne cells during nerve recovery after injury, and open the possibility for a therapeutic use of ApoD as a regeneration-promoting agent.
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影响因子：
3.5
作者：
Kobayashi, Hideo;Chattopadhyay, Sharmila;Kato, Kinshi;Dolkas, Jennifer;Kikuchi, Shin-ichi;Myers, Robert R.;Shubayev, Veronica I.
通讯作者：
Shubayev, Veronica I.
影响因子：
4.5
作者：
Hull-Thompson J;Muffat J;Sanchez D;Walker DW;Benzer S;Ganfornina MD;Jasper H
通讯作者：
Jasper H
影响因子：
6.2
作者：
Ganfornina, Maria D.;Do Carmo, Sonia;Sanchez, Diego
通讯作者：
Sanchez, Diego
影响因子：
6.2
作者：
Bajo-Graneras, Raquel;Ganfornina, Maria D.;Sanchez, Diego
通讯作者：
Sanchez, Diego
影响因子：
7.8
作者：
Ganfornina, Maria D.;Do Carmo, Sonia;Sanchez, Diego
通讯作者：
Sanchez, Diego