去甲肾上腺素和α-肾上腺素受体在急性应激诱导的粒细胞和单核细胞变化中的作用。
The Role of Norepinephrine and α-Adrenergic Receptors in Acute Stress-Induced Changes in Granulocytes and Monocytes.
机构信息
From the Biological Work and Health Psychology (Beis, Wirtz), Department of Psychology, University of Konstanz, Germany; Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine (von Känel), University Hospital Zurich; Department of Clinical Psychology and Psychotherapy (Heimgartner, Ehlert), University of Zurich; Biological and Health Psychology (Zuccarella-Hackl, Wirtz), University of Bern; Department of Neurorehabilitation (Zuccarella-Hackl), Zurich RehaZentrum, Wald, Switzerland; and Molecular Toxicology (Bürkle), Department of Biology, University of Konstanz, Germany.
出版信息
Psychosom Med. 2018 Sep;80(7):649-658. doi: 10.1097/PSY.0000000000000620.
OBJECTIVE
Acute stress induces redistribution of circulating leucocytes in humans. Although effects on lymphocytes as adaptive immune cells are well understood, the mechanisms underlying stress effects on granulocytes and monocytes as innate immune blood cells are still elusive. We investigated whether the stress hormone norepinephrine (NE) and α-adrenergic receptors (α-ADRs) may play a mediating role.
METHODS
In a stress study, we cross-sectionally tested 44 healthy men for associations between stress-induced NE increases and simultaneous granulocyte and monocyte cell count increases, as measured immediately before and several times after the Trier Social Stress Test. In a subsequent infusion study, 21 healthy men participated in three different experimental trials with sequential infusions of 1- and 15-minute duration with varying substances (saline as placebo, the nonspecific α-ADR blocker phentolamine [2.5 mg/min], and NE [5 μg/min]): trial 1 = saline+saline, trial 2 = saline+NE, trial 3 = phentolamine+NE. Granulocyte and monocyte cell numbers were assessed before, immediately after, 10 minutes, and 30 minutes after infusion procedures.
RESULTS
In the stress study, higher NE related to higher neutrophil stress changes (β = .31, p = .045, R change = .09), but not epinephrine stress changes. In the infusion study, saline+NE induced significant increases in neutrophil (F(3/60) = 43.50, p < .001, η = .69) and monocyte (F(3/60) = 18.56, p < .001, η = .48) numbers compared with saline+saline. With phentolamine+NE, neutrophil (F(3/60) = 14.41, p < .001, η = .42) and monocyte counts (F(2.23/44.6) = 4.32, p = .016, η = .18) remained increased compared with saline+saline but were lower compared with saline+NE (neutrophils: F(3/60) = 19.55, p < .001, η = .494, monocytes: F(3/60) = 2.54, p = .065, η = .11) indicating partial mediation by α-ADRs. Trials did not differ in eosinophil and basophil count reactivity.
CONCLUSIONS
Our findings suggest that NE-induced immediate increases in neutrophil and monocyte numbers resemble psychosocial stress effects and can be reduced by blockade of α-ADRs.
目的
急性应激会导致人体循环白细胞重新分布。虽然人们对作为适应性免疫细胞的淋巴细胞的应激效应机制已有了解，但应激对作为固有免疫血细胞的粒细胞和单核细胞的作用机制仍不清楚。我们研究了应激激素去甲肾上腺素（NE）和α-肾上腺素能受体（α-ADR）是否可能发挥介导作用。
方法
在一项应激研究中，我们对 44 名健康男性进行了横断面测试，以检测应激诱导的 NE 增加与同时的粒细胞和单核细胞计数增加之间的关联，这些增加是在特里尔社会应激测试之前和之后多次测量的。在随后的输注研究中，21 名健康男性参加了三项不同的实验试验，其中包括持续 1 分钟和 15 分钟的不同物质输注（盐水作为安慰剂、非特异性α-ADR 阻滞剂苯肾上腺素[2.5 mg/min]和 NE[5μg/min]）：试验 1=盐水+盐水，试验 2=盐水+NE，试验 3=苯肾上腺素+NE。在输注程序之前、之后、10 分钟和 30 分钟评估粒细胞和单核细胞数量。
结果
在应激研究中，较高的 NE 与较高的中性粒细胞应激变化相关（β=0.31，p=0.045，R 变化=0.09），但与肾上腺素的应激变化无关。在输注研究中，与盐水+盐水相比，盐水+NE 诱导显著增加中性粒细胞（F(3/60)=43.50，p<0.001，η=0.69）和单核细胞（F(3/60)=18.56，p<0.001，η=0.48）数量。与苯肾上腺素+NE 相比，与盐水+盐水相比，中性粒细胞（F(3/60)=14.41，p<0.001，η=0.42）和单核细胞计数（F(2.23/44.6)=4.32，p=0.016，η=0.18）仍然增加，但与盐水+NE 相比降低，表明α-ADR 存在部分介导作用。试验在嗜酸性粒细胞和嗜碱性粒细胞计数反应方面没有差异。
结论
我们的发现表明，NE 诱导的中性粒细胞和单核细胞数量的即刻增加类似于社会心理应激效应，并且可以通过阻断α-ADR 来减少。
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