Activation of the Macrophage α7 Nicotinic Acetylcholine Receptor and Control of Inflammation.
Activation of the Macrophage α7 Nicotinic Acetylcholine Receptor and Control of Inflammation.
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DOI：
10.1007/s11481-015-9601-5
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发表时间：
2015-09
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影响因子：
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通讯作者：
Lasalde-Dominicci JA
中科院分区：
文献类型：
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作者：
Báez-Pagán CA;Delgado-Vélez M;Lasalde-Dominicci JA
对刺激的炎症反应是身体抵御外来威胁的基本防御。然而，不受控制的炎症可能导致严重的健康问题，这可能危及生命。α7烟碱乙酰胆碱受体是一种在神经系统和免疫系统中表达的配体门控离子通道，在炎症的控制中具有重要作用。乙酰胆碱、尼古丁或其他激动剂激活巨噬细胞α7受体，选择性地抑制促炎细胞因子的产生，同时保持抗炎细胞因子不受干扰。这一调控途径的神经调控是近年来发现的，并将其命名为胆碱能抗炎途径（CAP）。当传入迷走神经末梢被细胞因子或其他促炎刺激激活时，信息通过传入迷走神经传递，导致动作电位沿传出迷走神经纤维传递，最终导致乙酰胆碱激活巨噬细胞α7，抑制促炎细胞因子的产生。巨噬细胞α7活化调控促炎反应的机制是目前研究的热点，并获得了重要的见解。结果表明，激活巨噬细胞α7可通过抑制NF-κB核易位和激活JAK2/STAT3通路等途径控制炎症。虽然α7在神经元中被认为是配体门控离子通道，但全细胞膜片钳实验表明，α7的离子通道活性（定义为离子响应配体在膜上的易位）在白细胞中不存在，因此，离子通道活性通常被认为不是CAP运行所必需的。从这个角度来看，我们简要回顾巨噬细胞α7激活与炎症控制有关。并提供单通道电流作为证据，证明巨噬细胞中表达的α7在没有全细胞电流的情况下仍保持其离子转运活性，从而拓宽目前的观点。这种离子转移活性是否与CAP的正常运作或其他重要的生理过程有关仍不清楚。
Inflammatory responses to stimuli are essential body defenses against foreign threats. However, uncontrolled inflammation may result in serious health problems, which can be life-threatening. The α7 nicotinic acetylcholine receptor, a ligand-gated ion channel expressed in the nervous and immune systems, has an essential role in the control of inflammation. Activation of the macrophage α7 receptor by acetylcholine, nicotine, or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed. The neural control of this regulation pathway was discovered recently and it was named the cholinergic anti-inflammatory pathway (CAP). When afferent vagus nerve terminals are activated by cytokines or other pro-inflammatory stimuli, the message travels through the afferent vagus nerve, resulting in action potentials traveling down efferent vagus nerve fibers in a process that eventually leads to macrophage α7 activation by acetylcholine and inhibition of pro-inflammatory cytokines production. The mechanism by which activation of α7 in macrophages regulates pro-inflammatory responses is subject of intense research, and important insights have thus been made. The results suggest that activation of the macrophage α7 controls inflammation by inhibiting NF-κB nuclear translocation, and activating the JAK2/STAT3 pathway among other suggested pathways. While the α7 is well characterized as a ligand-gated ion channel in neurons, whole-cell patch clamp experiments suggest that α7’s ion channel activity, defined as the translocation of ions across the membrane in response to ligands, is absent in leukocytes, and therefore, ion channel activity is generally assumed not to be required for the operation of the CAP. In this perspective, we briefly review macrophage α7 activation as it relates to the control of inflammation, and broaden the current view by providing single-channel currents as evidence that the α7 expressed in macrophages retains its ion translocation activity despite the absence of whole-cell currents. Whether this ion-translocating activity is relevant for the proper operation of the CAP or other important physiological processes remains obscure.