Role of macrophages in mobilization of hematopoietic progenitor cells from bone marrow after hemorrhagic shock.
Role of macrophages in mobilization of hematopoietic progenitor cells from bone marrow after hemorrhagic shock.
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DOI：
10.1097/shk.0b013e318249b81d
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Fan J
中科院分区：
文献类型：
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作者：
Xiang M;Yuan Y;Fan L;Li Y;Li A;Yin L;Scott MJ;Xiao G;Billiar TR;Wilson MA;Fan J
造血祖细胞(HPC)从骨髓(BM)中的释放受到严格的动态平衡控制。在应激条件下，HPC从骨髓和出口迁移到循环中，参与免疫反应、伤口修复或组织再生。严重创伤和大手术引起的失血性休克(HS/R)促进骨髓HPC的动员，进而影响HS后的免疫反应。在本研究中，我们研究了HS/R对骨髓HPC动员的调节机制。利用小鼠HS/R模型，我们证明了内源性Alarmin分子高迁移率族蛋白1(HMGB1)以RAGE信号依赖的方式介导HS/R诱导的巨噬细胞(Mφ)分泌G-CSF。分泌的G-CSF反过来诱导骨髓中的HPC外流。我们还发现，儿茶酚胺激活M-β上的φ-肾上腺素能受体介导了HS/R诱导的HMGB1的释放。这些数据表明，HS/R是一种全球性的缺血/再灌注刺激，它通过一系列相互作用的途径来调节HPC的动员，这些途径包括神经内分泌和先天免疫系统，其中M-φ起核心作用。
The release of hematopoietic progenitor cells (HPC) from bone marrow (BM) is under tight homeostatic control. Under stress conditions, HPC migrate from BM and egress into circulation to participate in immune response, wound repair, or tissue regeneration. Hemorrhagic shock with resuscitation (HS/R), resulting from severe trauma and major surgery, promotes HPC mobilization from BM, which in turn affects post-HS immune responses. In this study, we investigated the mechanism of HS/R regulation of HPC mobilization from BM. Using a mouse HS/R model we demonstrate that the endogenous alarmin molecule high-mobility group box 1 (HMGB1) mediates HS/R-induced G-CSF secretion from macrophages (Mφ) in a RAGE signaling-dependent manner. Secreted G-CSF, in turn, induces HPC egress from BM. We also show that activation of β-adrenergic receptors on Mφ by catecholamine mediates the HS/R-induced release of HMGB1. These data indicate that HS/R, a global ischemia/reperfusion stimulus, regulates HPC mobilization through a series of interacting pathways that include neuro-endocrine and innate immune systems, in which Mφ play a central role.