Sympathetic stimulation facilitates thrombopoiesis by promoting megakaryocyte adhesion, migration, and proplatelet formation
Sympathetic stimulation facilitates thrombopoiesis by promoting megakaryocyte adhesion, migration, and proplatelet formation
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交感神经刺激通过促进巨核细胞粘附、迁移和前血小板形成来促进血小板生成
DOI：
10.1182/blood-2015-07-660746
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发表时间：
2016-02-25
期刊：
影响因子：
20.3
通讯作者：
Wang, Junping
中科院分区：
文献类型：
--
作者：
Chen, Shilei;Du, Changhong;Wang, Junping
交感神经刺激对血小板生成的影响尚不清楚。在这里，我们证明，持续的噪音和力竭运动都会提高正常和脾切除小鼠的外周血小板水平，但不会提高缺乏去甲肾上腺素（NE）和肾上腺素（EPI）的多巴胺β-羟化酶缺陷（Dbh（-/-））小鼠的外周血小板水平。进一步研究表明，通过注射NE或EPI刺激交感神经，可显着促进6.0 Gy全身照射引起的血小板减少症小鼠和10.0 Gy致死照射后接受骨髓移植的小鼠的血小板恢复。不利的是，交感神经应激刺激的血小板生成也可能通过增加载脂蛋白E缺陷(ApoE(-/-))小鼠中血小板的数量和活性而促进动脉粥样硬化的发病机制。体外研究表明，除了CD34+细胞的扩增外，NE和EPI还促进巨核细胞粘附、迁移和前血小板形成(PPF)，从而促进血小板生成。研究发现α2-肾上腺素受体介导的细胞外信号调节激酶1/2（ERK1/2）激活参与NE和EPI诱导的巨核细胞粘附和迁移，PPF受ERK1/2激活介导的RhoA GTPase信号传导调节。我们的数据深入描述了交感神经刺激在血小板生成调节中的作用，并重新评估了其病理生理学意义。
The effect of sympathetic stimulation on thrombopoiesis is not well understood. Here, we demonstrate that both continual noise and exhaustive exercise elevate peripheral platelet levels in normal and splenectomized mice, but not in dopamine beta-hydroxylase-deficient (Dbh(-/-)) mice that lack norepinephrine (NE) and epinephrine (EPI). Further investigation demonstrates that sympathetic stimulation via NE or EPI injection markedly promotes platelet recovery in mice with thrombocytopenia induced by 6.0 Gy of total-body irradiation and in mice that received bone marrow transplants after 10.0 Gy of lethal irradiation. Unfavorably, sympathetic stress-stimulated thrombopoiesis may also contribute to the pathogenesis of atherosclerosis by increasing both the amount and activity of platelets in apolipoprotein E-deficient (ApoE(-/-)) mice. In vitro studies reveal that both NE and EPI promote megakaryocyte adhesion, migration, and proplatelet formation (PPF) in addition to the expansion of CD34(+) cells, thereby facilitating platelet production. It is found that alpha 2-adrenoceptor-mediated extracellular signal-regulated kinase 1/2 (ERK1/2) activation is involved in NE-and EPI-induced megakaryocyte adhesion and migration, and PPF is regulated by ERK1/2 activation-mediated RhoA GTPase signaling. Our data deeply characterize the role of sympathetic stimulation in the regulation of thrombopoiesis and reevaluate its physiopathological implications.