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 β-adrenergic receptor blockade, which was accompanied with inhibition of neutrophil egress into the systemic circulation. Furthermore, systemic β-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 Cxcl1 expression in bone marrow endothelial cells in a β-adrenergic signaling-dependent manner, contributing to the recruitment of neutrophils at the onset of inflammation in vivo.

中文翻译：

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局部交感神经元在急性炎症发作时促进中性粒细胞从骨髓中排出

交感神经系统在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，尽管其在急性炎症期间免疫细胞迁移控制中的作用仍不清楚。在这项研究中，使用我们实验室建立的先进活体骨成像系统，我们证明了交感神经系统局部调节中性粒细胞从骨髓排出，以动员到炎症病灶。我们发现交感神经元位于骨髓腔内的血管附近；此外，在脂多糖 (LPS) 给药后，局部交感神经切除术延迟了中性粒细胞从骨髓中排出并增加了留在原位的中性粒细胞比例。我们还表明血管内皮细胞产生 CXC 基序趋化因子配体 1 (CXCL1)，它负责中性粒细胞从骨髓中排出。其表达在急性炎症期间上调，并被 β-肾上腺素能受体阻断抑制，同时抑制中性粒细胞进入体循环。此外，全身性 β-肾上腺素能信号阻断减少了在急性全身炎症条件下肺中中性粒细胞的募集。总之，这项研究的结果首先提出了一种新的调节系统，其中局部交感神经激活通过增强中性粒细胞的排出来促进中性粒细胞的排出。其表达在急性炎症期间上调，并被 β-肾上腺素能受体阻断抑制，同时抑制中性粒细胞进入体循环。此外，全身性 β-肾上腺素能信号阻断减少了在急性全身炎症条件下肺中中性粒细胞的募集。总之，这项研究的结果首先提出了一种新的调节系统，其中局部交感神经激活通过增强中性粒细胞的排出来促进中性粒细胞的排出。其表达在急性炎症期间上调，并被 β-肾上腺素能受体阻断抑制，同时抑制中性粒细胞进入体循环。此外，全身性 β-肾上腺素能信号阻断减少了在急性全身炎症条件下肺中中性粒细胞的募集。总之，这项研究的结果首先提出了一种新的调节系统，其中局部交感神经激活通过增强中性粒细胞的排出来促进中性粒细胞的排出。Cxcl1在骨髓内皮细胞中以 β-肾上腺素能信号依赖性方式表达，有助于在体内炎症开始时募集中性粒细胞。