Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor.
Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor.
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DOI：
10.4049/jimmunol.145.5.1430
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发表时间：
1990-09
影响因子：
4.4
通讯作者：
Robert N. Spengler;R. Allen;D. Remick;R. Strieter;S. L. Kunkel
中科院分区：
文献类型：
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作者：
Robert N. Spengler;R. Allen;D. Remick;R. Strieter;S. L. Kunkel
越来越多的证据支持神经内分泌激素可能参与免疫过程的假设。在我们的研究中，我们已经确定UK-14304 （UK）和去甲肾上腺素（NE），这两种α 2肾上腺素能激动剂，可以增加lps刺激的巨噬细胞（MO）的TNF。TNF生成的增加是浓度依赖性的，UK和NE的EC50分别为8.1 +/- 2.6和0.52 +/- 0.17 nM。α 2拮抗剂育亨宾（10(-6)M）使UK和NE的浓度效应曲线右移，新EC50分别为49.7 +/- 12.2 (p < 0.001) nM和10.3 +/- 22 nM。通过7 log LPS反应曲线评估UK对MO TNF生成的增强作用。在单个MO群体中，10 nM UK将LPS诱导的TNF曲线向左移动了8倍，在较低LPS浓度下，TNF产量增加最多。在转录水平上，Northern blot分析显示UK增加了lps诱导的TNF mRNA积累。育亨宾阻断了TNF mRNA积累的增加。通过证明α 2-肾上腺素能拮抗剂3h -育亨宾与MO制备的膜结合，证实了MO α -肾上腺素能受体的存在。这种结合是快速、饱和、可逆的，并可被UK、clonidine和酚妥拉明阻断。这些研究支持α 2肾上腺素能激动剂作为免疫染色化合物的作用，可能调节炎症反应期间细胞因子的产生。
Accumulating evidence supports the hypothesis that neuroendocrine hormones may participate in immunologic processes. In our study we have determined that UK-14304 (UK) and norepinephrine (NE), both alpha 2-adrenergic agonists, can augment LPS-stimulated TNF from elicited macrophages (MO). The increase in TNF production was concentration dependent with an EC50 for UK and NE of 8.1 +/- 2.6 and 0.52 +/- 0.17 nM, respectively. The concentration-effect curve for UK and NE was shifted to the right by the alpha 2-antagonist yohimbine (10(-6) M), with new EC50 of 49.7 +/- 12.2 (p less than 0.001) nM and 10.3 +/- 22 nM. The augmenting effect of UK on MO TNF production was assessed over a 7 log LPS response curve. Within a single population of MO 10 nM UK shifted the LPS-induced TNF curve eightfold to the left with the greatest increase in TNF production at lower LPS concentrations. At the transcriptional level, Northern blot analysis demonstrated that UK increased LPS-induced TNF mRNA accumulation. This augmentation in TNF mRNA accumulation was blocked by yohimbine. The presence of a MO alpha-adrenergic receptor was established by demonstrating binding of the alpha 2-adrenergic antagonist 3H-yohimbine to membranes prepared from MO. This binding was rapid, saturable, reversible, and blocked by UK, clonidine, and phentolamine. These investigations support the role of alpha 2 adrenergic agonists as immunostaining compounds that may regulate cytokine production during an inflammatory response.