Local sympathetic neurons promote neutrophil egress from the bone marrow at the onset of acute inflammation
Local sympathetic neurons promote neutrophil egress from the bone marrow at the onset of acute inflammation
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DOI：
10.1093/intimm/dxaa025
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发表时间：
2020-11-01
影响因子：
4.4
通讯作者：
Ishii, Masaru
中科院分区：
文献类型：
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作者：
Ao, Tomoka;Kikuta, Junichi;Ishii, Masaru
交感神经系统在体内稳态条件下免疫细胞的分化、成熟和募集以及对环境刺激的反应中起着关键作用，但它在急性炎症中对免疫细胞的迁移控制中的作用尚不清楚。在这项研究中，利用我们实验室建立的先进的活体骨成像系统，我们证明了交感神经系统局部调节中性粒细胞从骨髓中流出，以动员到炎症灶。我们发现交感神经元位于骨髓腔中靠近血管的位置；此外，在给予脂多糖(LPS)后，局部交感神经切除推迟了中性粒细胞从骨髓中流出，并增加了中性粒细胞留在原地的比例。我们还发现，血管内皮细胞产生C-X-C基序趋化因子配体1(CXCL1)，负责中性粒细胞从骨髓中流出。在急性炎症过程中，其表达上调，并被β-肾上腺素能受体阻滞剂抑制，同时抑制中性粒细胞进入体循环。此外，全身β-肾上腺素能信号阻断减少了急性全身炎症条件下中性粒细胞在肺内的募集。综上所述，本研究结果首次提出了一种新的调节系统，在该系统中，局部交感神经激活以β-肾上腺素能信号依赖的方式增强骨髓内皮细胞中CxCL/的表达，促进中性粒细胞的外流，从而在体内炎症开始时促进中性粒细胞的募集。
The sympathetic nervous system plays critical roles in the differentiation, maturation and recruitment of immune cells under homeostatic conditions, and in responses to environmental stimuli, although its role in the migratory control of immune cells during acute inflammation remains unclear. In this study, using an advanced intravital bone imaging system established in our laboratory, we demonstrated that the sympathetic nervous system locally regulates neutrophil egress from the bone marrow for mobilization to inflammatory foci. We found that sympathetic neurons were located close to blood vessels in the bone marrow cavity; moreover, upon lipopolysaccharide (LPS) administration, local sympathectomy delayed neutrophil egress from the bone marrow and increased the proportion of neutrophils that remained in place. We also showed that vascular endothelial cells produced C-X-C motif chemokine ligand 1 (CXCL1), which is responsible for neutrophil egress out of the bone marrow. Its expression was up-regulated during acute inflammation, and was suppressed by beta-adrenergic receptor blockade, which was accompanied with inhibition of neutrophil egress into the systemic circulation. Furthermore, systemic beta-adrenergic signaling blockade decreased the recruitment of neutrophils in the lung under conditions of acute systemic inflammation.Taken together, the results of this study first suggested a new regulatory system, wherein local sympathetic nervous activation promoted neutrophil egress by enhancing Cxcl/ expression in bone marrow endothelial cells in a beta-adrenergic signaling-dependent manner, contributing to the recruitment of neutrophils at the onset of inflammation in vivo.