Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis.
Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis.
复制标题
DOI：
10.1084/jem.20052362
复制
发表时间：
2006-07-10
期刊：
影响因子：
--
通讯作者：
Ulloa L
中科院分区：
文献类型：
--
作者：
Huston JM;Ochani M;Rosas-Ballina M;Liao H;Ochani K;Pavlov VA;Gallowitsch-Puerta M;Ashok M;Czura CJ;Foxwell B;Tracey KJ;Ulloa L
先天性免疫系统通过网状内皮系统的专门器官（包括肺、肝和脾）保护免受感染和组织损伤。中枢神经系统通过迷走神经调节先天性免疫反应，这种机制称为胆碱能神经通路。迷走神经刺激通过α7烟碱乙酰胆碱受体亚单位的信号传导抑制促炎细胞因子的产生。以前，胆碱能神经递质通路和网状内皮系统之间的功能关系是未知的。在这里，我们表明，迷走神经刺激未能抑制肿瘤坏死因子（TNF）的生产在脾切除动物在致命的内毒素血症。腹腔总神经的选择性损伤通过迷走神经刺激消除了TNF抑制，表明胆碱能通路在功能上通过迷走神经的该分支硬连线到脾脏。尼古丁（一种模拟迷走神经刺激的α7激动剂）给药可增加脾切除小鼠中促炎细胞因子的产生和多微生物脓毒症的致死率，表明脾脏对胆碱能通路的保护性反应至关重要。这些结果揭示了神经和先天免疫系统之间的特异性生理联系，可以通过迷走神经电刺激或α7激动剂给药来抑制感染和组织损伤期间促炎细胞因子的产生。
The innate immune system protects against infection and tissue injury through the specialized organs of the reticuloendothelial system, including the lungs, liver, and spleen. The central nervous system regulates innate immune responses via the vagus nerve, a mechanism termed the cholinergic antiinflammatory pathway. Vagus nerve stimulation inhibits proinflammatory cytokine production by signaling through the α7 nicotinic acetylcholine receptor subunit. Previously, the functional relationship between the cholinergic antiinflammatory pathway and the reticuloendothelial system was unknown. Here we show that vagus nerve stimulation fails to inhibit tumor necrosis factor (TNF) production in splenectomized animals during lethal endotoxemia. Selective lesioning of the common celiac nerve abolishes TNF suppression by vagus nerve stimulation, suggesting that the cholinergic pathway is functionally hard wired to the spleen via this branch of the vagus nerve. Administration of nicotine, an α7 agonist that mimics vagus nerve stimulation, increases proinflammatory cytokine production and lethality from polymicrobial sepsis in splenectomized mice, indicating that the spleen is critical to the protective response of the cholinergic pathway. These results reveal a specific, physiological connection between the nervous and innate immune systems that may be exploited through either electrical vagus nerve stimulation or administration of α7 agonists to inhibit proinflammatory cytokine production during infection and tissue injury.
登录
查看更多内容
影响因子：
3
作者：
Spanaki, MV;Allen, LS;Morris, GL
通讯作者：
Morris, GL
DOI：
10.1084/jem.20040463
发表时间：
2005-04-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Saeed RW;Varma S;Peng-Nemeroff T;Sherry B;Balakhaneh D;Huston J;Tracey KJ;Al-Abed Y;Metz CN
通讯作者：
Metz CN
DOI：
10.1152/ajpregu.2000.279.3.r997
发表时间：
2000-09-01
影响因子：
2.8
作者：
Dixon, KD;Williams, FE;Gietzen, DW
通讯作者：
Gietzen, DW
影响因子：
6.4
作者：
Ge, YM;Ezzell, RM;Warren, HS
通讯作者：
Warren, HS
影响因子：
37.8
作者：
Guarini, S;Altavilla, D;Squadrito, F
通讯作者：
Squadrito, F