Chronic variable stress activates hematopoietic stem cells.
Chronic variable stress activates hematopoietic stem cells.
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作者：
暴露于心理社会压力是许多疾病的危险因素，包括动脉粥样硬化。虽然尚未完全理解，但心理和免疫系统之间的相互作用提供了一种将压力与疾病发生和发展联系起来的潜在机制。已知的大脑和免疫系统之间的串扰包括下丘脑-垂体-肾上腺轴，其集中驱动肾上腺皮质中的糖皮质激素产生，以及交感神经-肾上腺-髓质轴，其控制应激诱导的儿茶酚胺释放以支持战斗或逃跑反射。然而，慢性应激是否会改变造血干细胞的活性仍不清楚。在这里，我们表明，压力增加这些最原始的祖细胞的增殖，引起更高水平的疾病促进炎性白细胞。我们发现，慢性应激诱导单核细胞增多症和嗜中性粒细胞增多症。在研究小鼠白细胞增多的来源时，我们发现应激激活了上游造血干细胞。交感神经纤维释放过剩的去甲肾上腺素，其使用β3肾上腺素能受体向骨髓小生境细胞发出信号以降低CXCL 12水平。因此，升高的造血干细胞增殖增加嗜中性粒细胞和炎性单核细胞的输出。当易患动脉粥样硬化的ApoE−/−小鼠遇到慢性应激时，加速的造血促进了与导致人类心肌梗死和中风的易损病变相关的斑块特征。
Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. While incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known crosstalk between the brain and immune system includes the hypothalamic–pituitary–adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic–adrenal–medullary axis, which controls stress–induced catecholamine release in support of the fight–or–flight reflex. It remains unknown however if chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive progenitors, giving rise to higher levels of disease–promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Sympathetic nerve fibers release surplus noradrenaline, which uses the β3 adrenergic receptor to signal bone marrow niche cells to decrease CXCL12 levels. Consequently, elevated hematopoietic stem cell proliferation increases output of neutrophils and inflammatory monocytes. When atherosclerosis–prone ApoE−/− mice encounter chronic stress, accelerated hematopoiesis promotes plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.
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影响因子：
5
作者：
COHEN, S;KAMARCK, T;MERMELSTEIN, R
通讯作者：
MERMELSTEIN, R
影响因子：
64.5
作者：
Moore KJ;Tabas I
通讯作者：
Tabas I
DOI：
10.1111/j.1538-7836.2009.03423.x
发表时间：
2009-07
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Randolph GJ
通讯作者：
Randolph GJ
影响因子：
20.3
作者：
Eash, Kyle J.;Means, Jacquelyn M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ