Dual cholinergic signals regulate daily migration of hematopoietic stem cells and leukocytes
Dual cholinergic signals regulate daily migration of hematopoietic stem cells and leukocytes
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DOI：
10.1182/blood-2018-08-867648
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发表时间：
2019-01-17
期刊：
影响因子：
20.3
通讯作者：
Mendez-Ferrer, Simon
中科院分区：
文献类型：
--
作者：
Garcia-Garcia, Andres;Korn, Claudia;Mendez-Ferrer, Simon
造血干细胞和祖细胞（HSPC）和白细胞在昼夜节律振荡之后在骨髓（BM）和外周血之间循环。自主交感神经去甲肾上腺素能信号已被证明可调节HSPC和白细胞运输，但胆碱能分支的作用仍有待研究。我们研究了胆碱能神经系统在调节小鼠HSPCs和白细胞昼夜交通中的作用。我们在这里表明，自主胆碱能神经系统（包括副交感神经和交感神经）双重调节HSPCs和白细胞的日常迁移。在夜间，中枢副交感神经胆碱能信号抑制交感神经去甲肾上腺素能张力并减少HSPC和白细胞的BM排出。然而，在白天，去抑制的交感神经去甲肾上腺素能活性通过β（3）-肾上腺素能受体引起HSPC和白细胞的主要BM排出。这种出口由光触发的交感胆碱能活性局部支持，其抑制BM血管细胞粘附和归巢。总之，中枢（副交感神经）和局部（交感神经）胆碱能信号调节循环HSPC和白细胞的昼夜振荡。这项研究展示了自主神经系统的两个分支如何合作来协调HSPC和白细胞的日常流量。
Hematopoietic stem and progenitor cells (HSPCs) and leukocytes circulate between the bone marrow (BM) and peripheral blood following circadian oscillations. Autonomic sympathetic noradrenergic signals have been shown to regulate HSPC and leukocyte trafficking, but the role of the cholinergic branch has remained unexplored. We have investigated the role of the cholinergic nervous system in the regulation of day/night traffic of HSPCs and leukocytes in mice. We show here that the autonomic cholinergic nervous system (including parasympathetic and sympathetic) dually regulates daily migration of HSPCs and leukocytes. At night, central parasympathetic cholinergic signals dampen sympathetic noradrenergic tone and decrease BM egress of HSPCs and leukocytes. However, during the daytime, derepressed sympathetic noradrenergic activity causes predominant BM egress of HSPCs and leukocytes via beta(3)-adrenergic receptor. This egress is locally supported by light-triggered sympathetic cholinergic activity, which inhibits BM vascular cell adhesion and homing. In summary, central (parasympathetic) and local (sympathetic) cholinergic signals regulate day/night oscillations of circulating HSPCs and leukocytes. This study shows how both branches of the autonomic nervous system cooperate to orchestrate daily traffic of HSPCs and leukocytes.