Suppression of NK cell activity and of resistance to metastasis by stress:: A role for adrenal catecholamines and β-adrenoceptors
Suppression of NK cell activity and of resistance to metastasis by stress:: A role for adrenal catecholamines and β-adrenoceptors
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DOI：
10.1159/000054276
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发表时间：
2000-01-01
影响因子：
2.4
通讯作者：
Shakhar, K
中科院分区：
文献类型：
--
作者：
Ben-Eliyahu, S;Shakhar, G;Shakhar, K
虽然急性应激已被报道抑制自然杀伤细胞活性（NKA）和宿主对转移的抵抗力，但尚不清楚交感神经系统（SNS）是否在这些作用中起作用。目前在Fischer 344大鼠中进行的研究评估了肾上腺儿茶酚胺和β（1）-和β（2）-肾上腺素受体在介导游泳应激的这些有害作用中的参与。除了评估游泳应激后NK细胞的数量和活性外，我们还使用了基于MADB 106乳腺癌细胞系的肿瘤模型：这种同系肿瘤仅转移到肺，并且其肺肿瘤滞留（LTR）和转移性定殖对NKA高度敏感。该发现表明应激增加了接种后24小时评估的LTR和肺转移的数量，3周后计算。神经节阻滞剂氯异山达明（3 mg/kg i. p.）可减弱或完全消除这些作用，通过肾上腺去髓鞘、通过选择性β-肾上腺素能拮抗剂（纳多洛尔，0.4 mg/kg）、以及通过选择性β（1）-（阿替洛尔，1-6 mg/kg）和选择性β（2）-拮抗剂（丁氧胺4-32 mg/kg或ICI-118，551 0.3-8 mg/kg）的相加。应激也抑制NKA，肾上腺去髓鞘阻止了这种抑制。以生理学相关剂量给予肾上腺素（0.1-1 mg/kg）或β-肾上腺素能激动剂（metaproterenol，0.8 mg/kg），以剂量依赖性方式抑制NKA，并将LTR增加至游泳应激特征性水平。综上所述，这些发现表明，急性应激通过从肾上腺释放儿茶酚胺并激活β（1）-和β（2）-肾上腺素受体，抑制NKA，从而损害对NK敏感性转移的抵抗。版权所有（C）2000 S. Karger AG，巴塞尔。
Although acute stress has been reported to suppress natural killer cell activity (NKA) and host resistance to metastasis, it is unclear whether the sympathetic nervous system (SNS) has a role in these effects. The current study in Fischer 344 rats assessed the involvement of adrenal catecholamines and beta (1)- and beta (2)-adrenoceptors in mediating these deleterious effects of swim stress. In addition to assessing the number and activity of NK cells following swim stress, we used a tumor model based on the MADB106 mammary adenocarcinoma line: this syngeneic tumor metastasizes only to the lungs, and its lung tumor retention (LTR) and metastatic colonization are highly sensitive to NKA, The findings indicate that stress increased both LTR, assessed 24 h after inoculation, and the number of lung metastases, counted 3 weeks later. These effects were attenuated or completely abolished by the ganglionic blocker chlorisondamine (3 mg/kg i.p.), by adrenal demedullation, by a selective beta -adrenergic antagonist (nadolol, 0.4 mg/kg), and additively by a selective beta (1)- (atenolol, 1-6 mg/kg) and a selective beta (2)- antagonist (either butoxamine 4-32 mg/kg or ICI-118,551 0.3-8 mg/kg). Stress also suppressed NKA, and adrenal demedullation prevented this suppression. Administration of adrenaline (0.1-1 mg/kg) or of a beta -adrenergic agonist (metaproterenol, 0.8 mg/kg), in physiologically relevant doses, suppressed NKA in a dose-dependent manner, and increased LTR to levels characteristic of swim stress. Taken together, these findings suggest that acute stress, by releasing catecholamines from the adrenal glands and activating beta (1)- and beta (2)-adrenoceptors, suppresses NKA and consequently compromises resistance to NK-sensitive metastasis. Copyright (C) 2000 S. Karger AG, Basel.