NEUROIMMUNOMODULATION PATCH CLAMP STUDIES

这项建议的长期目标是加深我们对 的细胞和亚细胞机制的基础 神经免疫调节。 越来越多的证据支持这样一种观点：神经系统 与免疫系统相互作用。结果来自解剖学、生物化学 生理学研究都表明神经物质的作用， 几种淋巴细胞上的神经肽、神经递质和激素 功能。 关于这些物质如何调节淋巴细胞功能的一个想法是 根据观察，淋巴细胞的激活，有丝分裂和 容量调节依赖于离子通量，神经肽和 已被证明可以调节免疫反应的激素也 调节可兴奋细胞中的钾和钙通道。因此，一个 神经系统调节免疫的可能机制 反应是通过调节淋巴细胞离子通道和电流来实现的。我们 因此建议研究免疫活性的作用 离子通道和电流上的递质、多肽和激素 淋巴细胞的数量。 具体目标是：1)测量，使用整个单元配置 在膜片钳技术(Hamil等人，1981)的基础上， 小鼠和人T淋巴细胞活性及其调节作用的研究 这种活动受神经递质、神经肽和激素的影响。2)考核 无论是静息还是增殖的T细胞对 应用神经调节剂。3)确定第二信使系统 参与调节作用(S)观察到。 这些研究将为我们了解 参与淋巴细胞功能和功能的信号转导途径 免疫抑制或免疫增强剂的调控和设计 基于它们的通道阻挡特性。

The long-term objective of this proposal is to further our understanding of the cellular and subcellular mechanisms underlying the process of neuroimmunomodulation. Evidence has accumulated to support the idea that the nervous system interacts with the immune system. Results from anatomical, biochemical and physiological studies all suggest an effect of neural substance, neuropeptides, neurotransmitters and hormones, on several lymphocyte functions. An idea of the way these substances can modulate lymphocyte function is based on the observation that lymphocyte activation, mitogenesis and volume regulation are dependent on ionic fluxes, and neuropeptides and hormones that have been shown to modulate the immune response also modulate potassium and calcium channels in excitable cells. Thus, a possible mechanism by which the nervous system regulates the immune response is by modulating lymphocyte ion channels and currents. We therefore propose to study the effects of immunologically active transmitters, peptides and hormones on the ionic channels and currents of lymphocytes. The specific aims are: 1) Measure, using the whole cell configuration of the patch clamp technique (Hamil, et al., 1981), the electrical activity of murine and human T lymphocytes and study the modulation of this activity by neurotransmitters, neuropeptides and hormones. 2) Assess whether resting or proliferating T cells are more responsive to the applied neuromodulators. 3) Determine the second messenger system involved in the modulatory effect(s) observed. These studies will provide relevant information for our understanding of the signal transduction pathways involved in lymphocyte function and regulation and the design of immunosuppressive or immunoenhancing agents on the basis of their channel blocking properties.