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A Novel Evidence That Mannan Binding Lectin (MBL) Pathway of Complement Cascade Activation is Involved in Homing and Engraftment of Hematopoietic Stem Progenitor Cells (HSPCs).
Stem Cell Reviews and Reports ( IF 4.8 ) Pub Date : 2020-05-14 , DOI: 10.1007/s12015-020-09983-8
Mateusz Adamiak 1 , Monika Cymer 1 , Krzysztof Anusz 2 , Michał Tracz 2 , Mariusz Z Ratajczak 1, 3
Affiliation  

Delayed homing and engraftment of hematopoietic stem progenitor cells (HSPCs) or even failure to engraft at all is significant clinical problem after hematopoietic transplant. Therefore, in order to develop more efficient homing and engraftment facilitating strategies it is important to learn more about this process. Our team has postulated that myeloablative conditioning for transplantation induces in bone marrow (BM) microenvironment a state of sterile inflammation in which elements of innate immunity activated by radio- or chemotherapy conditioning for transplant play an important role. In frame with this claim we reported that a significant role in this process plays activation of complement cascade (ComC). Accordingly, mice that that lack a fifth component (C5) of ComC turned out to engraft poorly with normal syngeneic BM cells as compared to normal control animals. In extension of our previous studies we provide for first time evidence that mannan binding lectin (MBL) pathway is involved in activation of ComC in myeloablated transplant recipient BM and thus plays an important role in homing and engraftment of HSPCs. To support this MBL-KO mice show significant defect in hematopoietic reconstitution after hematopoietic transplantation. This correlates with a decrease in expression of stromal derived factor-1 (SDF-1) and impaired activation of Nlrp3 inflammasome in irradiated BM of these mice.

中文翻译:

补体级联激活的甘露聚糖结合凝集素(MBL)途径参与造血干祖细胞(HSPCs)的归巢和植入的新证据。

造血干祖细胞(HSPC)的归巢和植入延迟,甚至根本无法植入,是造血干细胞移植后的重大临床问题。因此,为了制定更有效的归巢和嫁接促进策略,重要的是要更多地了解这一过程。我们的研究小组推测,用于移植的清髓条件会在骨髓(BM)微环境中诱导无菌炎症状态,在这种状态下,通过放射或化学疗法对移植进行激活的先天免疫成分起着重要的作用。为配合这一主张,我们报道了在该过程中的重要作用是补体级联反应(ComC)的激活。因此,与正常对照动物相比,缺乏ComC第五成分(C5)的小鼠无法正常移植同种BM细胞。在我们先前研究的扩展中,我们首次提供了甘露聚糖结合凝集素(MBL)途径参与了髓样移植受者BM中ComC的激活,因此在HSPC归巢和植入中起着重要作用。为了支持这一点,MBL-KO小鼠在造血移植后的造血重建中显示出明显的缺陷。这与这些小鼠辐照的BM中基质衍生因子1(SDF-1)的表达减少和Nlrp3炎性小体的激活受损有关。在我们先前研究的扩展中,我们首次提供了甘露聚糖结合凝集素(MBL)途径参与了髓样移植受者BM中ComC的激活,因此在HSPC归巢和植入中起着重要作用。为了支持这一点,在造血细胞移植后,小鼠在造血细胞重建中显示出明显的缺陷。这与这些小鼠辐照的BM中基质衍生因子1(SDF-1)的表达减少和Nlrp3炎性小体的激活受损有关。在我们先前研究的扩展中,我们首次提供了甘露聚糖结合凝集素(MBL)途径参与了髓样移植受者BM中ComC的激活,因此在HSPC归巢和植入中起着重要作用。为了支持这一点,MBL-KO小鼠在造血移植后的造血重建中显示出明显的缺陷。这与这些小鼠辐照的BM中基质衍生因子1(SDF-1)的表达减少和Nlrp3炎性小体的激活受损有关。
更新日期:2020-05-14
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