Novel evidence that the mannan-binding lectin pathway of complement activation plays a pivotal role in triggering mobilization of hematopoietic stem/progenitor cells by activation of both the complement and coagulation cascades.

Novel evidence that the mannan-binding lectin pathway of complement activation plays a pivotal role in triggering mobilization of hematopoietic stem/progenitor cells by activation of both the complement and coagulation cascades.
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DOI:
10.1038/leu.2016.278
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发表时间:
2017-01
期刊:
影响因子:
11.4
通讯作者:
--
中科院分区:
医学1区
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--
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造血干祖细胞(HSPC)在外周血(PB)中以低水平循环,并遵循昼夜节律的变化。1.越来越多的证据表明,它们以补体级联(ComC)依赖的方式从干细胞龛中流出显著增加。2在感染、组织或器官损伤期间,特别是在施用药理学药物(例如粒细胞集落刺激因子(G-CSF)或CXCR 4受体拮抗剂AMD 3100)之后,PB中循环的HSPC的数量增加,并且药理学动员是获得用于造血移植的HSPC的手段。3. ComC的激活途径有经典途径、甘露聚糖结合凝集素(MBL)途径和旁路途径。4通过经典C5转化酶激活ComC并产生ComC的第五组分(C5)的切割片段,例如C5 a、desArgC 5a和C5 b,引发HSPC从骨髓(BM)进入PB所需的事件。5最近的结果表明,凝血级联(CoaC)在动员过程中与ComC的激活平行激活,并起支持作用,因为凝血酶具有C5样转化酶活性。6尽管之前已经证明了ComC激活的需要以及补体激活的远端部分和C5切割片段的产生在执行动员中的关键作用,但是5只具有ComC基因突变的小鼠,
Hematopoietic stem progenitor cells (HSPCs) circulate at low levels in peripheral blood (PB) and follow changes in circadian rhythm. 1 Evidence has accumulated that their egress from stem cell niches is significantly augmented in a complement cascade (ComC)-dependent manner. 2 The number of HSPCs circulating in PB increases during infection, tissue or organ injuries and particularly after administration of pharmacological drugs, such as granulocyte-colony stimulating factor (G-CSF) or the CXCR4 receptor antagonist AMD3100, and pharmacological mobilization is a means to obtaining HSPCs for hematopoietic transplants. 3 However, the mobilization process is still not well understood.The ComC is activated by the classical, mannan-binding lectin (MBL) and alternative pathways. 4 Activation of the ComC and generation of cleavage fragments of the fifth component of the ComC (C5), such as C5a, desArgC5a and C5b, by classical C5 convertase initiates events that are required for egress of HSPCs from bone marrow (BM) into PB. 5 Recent results indicate that the coagulation cascade (CoaC) is activated in parallel with activation of the ComC during the mobilization process and plays a supportive role, because thrombin has ‘C5-likeL convertase activity. 6 Although a requirement for ComC activation and the pivotal roles of the distal part of complement activation and the generation of C5 cleavage fragments in executing mobilization have been previously demonstrated, 5 mice with mutations in
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