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粒细胞集落刺激因子体内应用对骨髓和外周血 NK 细胞的影响。

Effect of the in vivo application of granulocyte colony-stimulating factor on NK cells in bone marrow and peripheral blood.

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

Peking-Tsinghua Center for Life Sciences, Beijing, China.

出版信息

J Cell Mol Med. 2018 Jun;22(6):3025-3034. doi: 10.1111/jcmm.13539. Epub 2018 Mar 25.

Abstract

Granulocyte colony-stimulating factor (G-CSF) has been widely used in the field of allogeneic haematopoietic stem cell transplantation (allo-HSCT) for priming donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect stem cells more conveniently. Donor-derived natural killer (NK) cells have important antitumour functions and immune regulatory roles post-allo-HSCT. The aim of this study was to evaluate the effect of G-CSF on donors' NK cells in BM and PB. The percentage of NK cells among nuclear cells and lymphocyte was significantly decreased and led to increased ratio of T and NK cells in BM and PB post-G-CSF in vivo application. Relative expansion of CD56 NK cells led to a decreased ratio of CD56 and CD56 NK subsets in BM and PB post-G-CSF in vivo application. The expression of CD62L, CD54, CD94, NKP30 and CXCR4 on NK cells was significantly increased in PB after G-CSF treatment. G-CSF treatment decreased the IFN-γ-secreting NK population (NK1) dramatically in BM and PB, but increased the IL-13-secreting NK (NK2), TGF-β-secreting NK (NK3) and IL-10-secreting NK (NKr) populations significantly in BM. Clinical data demonstrated that higher doses of NK1 infused into the allograft correlated with an increased incidence of chronic graft-vs-host disease post-transplantation. Taken together, our results show that the in vivo application of G-CSF can modulate NK subpopulations, leading to an increased ratio of T and NK cells and decreased ratio of CD56 and CD56 NK cells as well as decreased NK1 populations in both PB and BM.

摘要

粒细胞集落刺激因子(G-CSF)已广泛应用于异基因造血干细胞移植(allo-HSCT)领域,通过刺激供体骨髓(BM)中的干细胞进入外周血(PB),以便更方便地采集干细胞。供体来源的自然杀伤(NK)细胞在 allo-HSCT 后具有重要的抗肿瘤功能和免疫调节作用。本研究旨在评估 G-CSF 对供者 BM 和 PB 中 NK 细胞的影响。结果显示,G-CSF 体内应用后,BM 和 PB 中核细胞和淋巴细胞中 NK 细胞的比例显著下降,导致 T 细胞和 NK 细胞的比例增加。CD56+NK 细胞的相对扩增导致 BM 和 PB 中 CD56+和 CD56-NK 亚群的比例降低。G-CSF 处理后,PB 中 NK 细胞上 CD62L、CD54、CD94、NKP30 和 CXCR4 的表达显著增加。G-CSF 处理后,BM 和 PB 中 IFN-γ 分泌 NK 细胞(NK1)显著减少,但显著增加了 IL-13 分泌 NK(NK2)、TGF-β 分泌 NK(NK3)和 IL-10 分泌 NK(NKr)。临床数据表明,移植后输注到同种异体移植物中的较高剂量 NK1 与慢性移植物抗宿主病的发生率增加相关。总之,我们的研究结果表明,G-CSF 的体内应用可以调节 NK 亚群,导致 PB 和 BM 中 T 细胞和 NK 细胞的比例增加,CD56+和 CD56-NK 细胞的比例降低,以及 NK1 细胞数量减少。

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