Bortezomib enhances G-CSF-induced hematopoietic stem cell mobilization by decreasing CXCL12 levels and increasing vascular permeability
Bortezomib enhances G-CSF-induced hematopoietic stem cell mobilization by decreasing CXCL12 levels and increasing vascular permeability
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DOI：
10.1016/j.exphem.2021.02.009
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发表时间：
2021-05-01
影响因子：
2.6
通讯作者：
Hara, Shuuji
中科院分区：
文献类型：
--
作者：
Matsumoto, Taichi;Takamatsu, Yasushi;Hara, Shuuji
硼替佐米（BTZ）已知增强由粒细胞集落刺激因子（G-CSF）诱导的造血干细胞和祖细胞（HSPC）的动员。然而，给予BTZ产生这种增强作用的最有效时间仍然存在争议，并且BTZ作用的确切机制知之甚少。我们在这篇文章中通过进行动物实验来解决这些问题。首先，与先前的研究一致，在采血前12小时给予BTZ对HSPC动员最有效;相反，在采血前3天给予BTZ对HSPC收获产生负面影响。接下来，在作用机制方面，G-CSF而不是BTZ下调HSPC上的极晚期抗原-4和骨髓（BM）基质细胞上的血管细胞粘附分子-1的表达;然而，有趣的是，G-CSF和BTZ均下调BM中的CXCL 12趋化因子表达。值得注意的是，BTZ治疗也增加了BM血管通透性。这些结果表明，BTZ的促动员作用可能涉及由G-CSF触发的HSPC与BM基质细胞的解离、BTZ引起的血管通透性增高以及G-CSF和BTZ伴随诱导的CXCL 12的下调。? 2021年由Elsevier Inc.出版代表ISEH？血液学和干细胞学会。
Bortezomib (BTZ) is known to enhance the mobilization of hematopoietic stem and progenitor cells (HSPCs) induced by granulocyte colony-stimulating factor (G-CSF). However, the most effective time at which to administer BTZ to produce this enhancing effect remains debatable, and the precise mechanism underlying the effect of BTZ is poorly understood. We addressed these questions in this article by performing animal experiments. First, in agreement with previous studies, BTZ administration 12 hours before blood collection was most effective for HSPC mobilization; in contrast, BTZ administration 3 days before blood collection negatively affected HSPC harvesting. Next, in terms of the mechanism of action, G-CSF, but not BTZ, downregulated the expression of very late antigen-4 on HSPCs and vascular cell adhesion molecule-1 on bone marrow (BM) stromal cells; however, intriguingly, both G-CSF and BTZ downregulated CXCL12 chemokine expression in BM. Notably, BTZ treatment also increased BM vascular permeability. These results suggest that the pro-mobilization effect of BTZ could involve the dissociation of HSPCs from BM stromal cells triggered by G-CSF, vascular hyperpermeability elicited by BTZ, and downregulation of CXCL12 concomitantly induced by G-CSF and BTZ. ? 2021 Published by Elsevier Inc. on behalf of ISEH ? Society for Hematology and Stem Cells.