Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Neuroimmunomodulation. 2010;17(5):298-304. doi: 10.1159/000292019. Epub 2010 Apr 17.
Reciprocal pathways of interaction between the nervous and immune systems during stress may be regulated by stress-induced circulating glucocorticoids that act via type II glucocorticoid receptors (GRs). The aim of the present study was to investigate the effect of restraint stress on GRs in lymphocytes and the role of the sympathetic system in this effect.
We used male Balb/c mice which were adrenalectomized 3 days before exposure to restraint stress (4 h). Specific binding of 3H-dexamethasone (Dex) and the expression of GR protein were measured in the cytosol of spleen cells.
Restraint stress caused a significant increase in the maximal binding of 3H-Dex to GRs in the cytosol of spleen cells but not in the binding affinity. In correlation with this increase in binding, restraint stress caused an increase in the amount of GR protein. To establish the relation of the nervous system in this stress response, we blocked the autonomic innervations to the spleen with the ganglionic blocker chlorisondamine. This blocker abrogated the stress-induced increase in the binding of 3H-Dex to GRs and in the GR protein levels. Abrogation of the stress response was also achieved by blocking beta-adrenergic receptors.
These results suggest that stress-induced increase in the level of GRs is mediated by the sympathetic nervous system via beta-adrenergic receptors. It is possible that stress modulation of lymphocyte GR levels may be implicated in the bidirectional communication between the nervous and the immune systems.
在应激过程中，神经系统和免疫系统之间的相互作用的反馈途径可能受到应激诱导的循环糖皮质激素的调节，后者通过 II 型糖皮质激素受体（GRs）起作用。本研究的目的是研究应激对淋巴细胞中 GRs 的影响，以及交感神经系统在这种作用中的作用。
我们使用雄性 Balb/c 小鼠，它们在暴露于束缚应激（4 小时）前 3 天进行肾上腺切除术。测量脾细胞胞浆中 3H-地塞米松（Dex）的特异性结合和 GR 蛋白的表达。
束缚应激导致脾细胞胞浆中 3H-Dex 与 GR 结合的最大结合显著增加，但结合亲和力没有变化。与这种结合增加相关，应激导致 GR 蛋白的量增加。为了确定神经系统在这种应激反应中的关系，我们用神经节阻滞剂氯苯乙胺阻断了对脾脏的自主神经支配。该阻滞剂消除了应激诱导的 3H-Dex 与 GR 结合以及 GR 蛋白水平的增加。通过阻断β-肾上腺素能受体也可以实现应激反应的阻断。
这些结果表明，应激诱导的 GR 水平增加是通过交感神经系统通过β-肾上腺素能受体介导的。应激调节淋巴细胞 GR 水平可能与神经系统和免疫系统之间的双向通讯有关。
