Pannexin-1 channel "fuels" by releasing ATP from bone marrow cells a state of sterile inflammation required for optimal mobilization and homing of hematopoietic stem cells.
Pannexin-1 channel "fuels" by releasing ATP from bone marrow cells a state of sterile inflammation required for optimal mobilization and homing of hematopoietic stem cells.
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DOI：
10.1007/s11302-020-09706-1
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发表时间：
2020-09
影响因子：
3.5
通讯作者：
Adamiak M
中科院分区：
文献类型：
--
作者：
Cymer M;Brzezniakiewicz-Janus K;Bujko K;Thapa A;Ratajczak J;Anusz K;Tracz M;Jackowska-Tracz A;Ratajczak MZ;Adamiak M
在从骨髓（BM）到外周血（PB）的药理学动员之后有效收获造血干/祖细胞（HSPC）以及随后这些细胞的适当归巢和植入对于来自造血移植的临床结果至关重要。由于细胞外三磷酸腺苷（eATP）在这两个过程中起着重要的作用，作为骨髓微环境中无菌炎症的激活剂，我们专注于Pannexin-1通道在ATP分泌中的作用，以触发HSPC从BM进入PB以及在移植到骨髓清除受体后归巢到BM小生境的反向过程中。我们采用了针对Pannexin-1通道的特异性阻断肽，并注意到HSPC以及其他类型的BM驻留干细胞（包括间充质基质细胞（MSC），内皮祖细胞（EPC）和非常小的胚胎样干细胞（VSEL））的动员效率降低。为了更好地解释Pannexin-1的作用，我们报道了eATP激活了富含粒细胞和单核细胞的Gr-1+和CD 11b+细胞中的Nlrp 3炎性体。这导致释放激活HSPC从BM最佳流出所需的补体级联（ComC）的补体相关分子模式分子（DAMP）和线粒体DNA（miDNA）。另一方面，移植受体小鼠中的Pannexin-1通道阻断导致HSPC的归巢和植入缺陷。基于此，Pannexin-1通道作为eATP的来源在HSPCs的运输中起着重要的作用。本文的在线版本（10.1007/s11302-020-09706-1）包含补充材料，可供授权用户使用。
An efficient harvest of hematopoietic stem/progenitor cells (HSPCs) after pharmacological mobilization from the bone marrow (BM) into peripheral blood (PB) and subsequent proper homing and engraftment of these cells are crucial for clinical outcomes from hematopoietic transplants. Since extracellular adenosine triphosphate (eATP) plays an important role in both processes as an activator of sterile inflammation in the bone marrow microenvironment, we focused on the role of Pannexin-1 channel in the secretion of ATP to trigger both egress of HSPCs out of BM into PB as well as in reverse process that is their homing to BM niches after transplantation into myeloablated recipient. We employed a specific blocking peptide against Pannexin-1 channel and noticed decreased mobilization efficiency of HSPCs as well as other types of BM-residing stem cells including mesenchymal stroma cells (MSCs), endothelial progenitors (EPCs), and very small embryonic-like stem cells (VSELs). To explain better a role of Pannexin-1, we report that eATP activated Nlrp3 inflammasome in Gr-1+ and CD11b+ cells enriched for granulocytes and monocytes. This led to release of danger-associated molecular pattern molecules (DAMPs) and mitochondrial DNA (miDNA) that activate complement cascade (ComC) required for optimal egress of HSPCs from BM. On the other hand, Pannexin-1 channel blockage in transplant recipient mice leads to a defect in homing and engraftment of HSPCs. Based on this, Pannexin-1 channel as a source of eATP plays an important role in HSPCs trafficking. The online version of this article (10.1007/s11302-020-09706-1) contains supplementary material, which is available to authorized users.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
3.2
作者：
Hoggatt J;Pelus LM
通讯作者：
Pelus LM
影响因子：
1.5
作者：
Henig I;Zuckerman T
通讯作者：
Zuckerman T
影响因子：
11.4
作者：
通讯作者：
--
影响因子：
11.4
作者：
Borkowska, S.;Suszynska, M.;Ratajczak, M. Z.
通讯作者：
Ratajczak, M. Z.