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异基因造血干细胞移植后中性粒细胞和不同单核细胞亚群的重建和功能分析。

Reconstitution and functional analyses of neutrophils and distinct subsets of monocytes after allogeneic stem cell transplantation.

机构信息

Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07740, Jena, Germany.

出版信息

J Cancer Res Clin Oncol. 2011 Sep;137(9):1293-300. doi: 10.1007/s00432-011-0989-x. Epub 2011 Jun 29.

DOI:10.1007/s00432-011-0989-x
PMID:21713449
Abstract

PURPOSE

The aim of the study was to investigate the recovery of the innate immune system within the first 100 days after allogeneic peripheral blood stem cell transplantation (PBSCT) and to elucidate a potential correlation with such important events as severe infectious complications or graft-versus-host disease (GvHD).

METHODS

In 30 consecutive patients who underwent allogeneic PBSCT, absolute numbers of neutrophils and monocytes were determined and different functional analyses performed at different time points (day +30, +60 and +90, respectively). The capacity to phagocyte Escherichia coli (E. coli) as well as the induction of oxidative burst after incubation with different stimuli (Phorbol-12-myristate-13-acetate; PMA, the chemotactic peptide N-formyl-Met-Leu-Phe; f-MLP or opsonized E. coli) were analysed after engraftment.

RESULTS

There was a rapid reconstitution concerning the capability of both neutrophils and monocytes to phagocyte E. coli without a significant increase between day +30 and +90. In contrast, a twofold increase of monocyte oxidative burst after incubation with PMA at day +90 was observed (P = 0.017). Furthermore, the ability of neutrophils to induce oxidative burst after ingestion with E. coli was impaired on day +30 with a significant functional reconstitution on day +60 (P = 0.01). The oxidative burst activity following incubation with f-MLP did not show significant changes after stem cell engraftment. Analysis of numeric reconstitution of CD14+CD16+ monocytes demonstrated a potential correlation with a decreased incidence of chronic GvHD.

CONCLUSION

The functional recovery of neutrophils and monocytes in the early period after allogeneic PBSCT differs not only concerning phagocytosis and oxidative burst but also with respect to the stimulus and the cell population that was analysed for oxidative burst activity. The subset of CD16+CD14+ monocytes might be a predictor for a reduced risk of chronic GvHD.

摘要

目的

本研究旨在探讨异基因外周血造血干细胞移植(PBSCT)后 100 天内固有免疫系统的恢复情况,并阐明其与严重感染并发症或移植物抗宿主病(GVHD)等重要事件之间的潜在相关性。

方法

在 30 例连续接受异基因 PBSCT 的患者中,分别在不同时间点(移植后第 30、60 和 90 天)测定中性粒细胞和单核细胞的绝对数,并进行不同的功能分析。在移植后,分析吞噬大肠杆菌(E. coli)的能力以及孵育不同刺激物(佛波醇 12-肉豆蔻酸 13-乙酸酯;PMA、趋化肽 N-甲酰基-Met-Leu-Phe;f-MLP 或调理大肠杆菌)后诱导氧化爆发的能力。

结果

中性粒细胞和单核细胞吞噬大肠杆菌的能力迅速恢复,但在第 30 天和第 90 天之间没有明显增加。相比之下,第 90 天孵育 PMA 后单核细胞氧化爆发增加了两倍(P = 0.017)。此外,第 30 天中性粒细胞吞噬大肠杆菌后诱导氧化爆发的能力受损,第 60 天功能恢复显著(P = 0.01)。孵育 f-MLP 后,中性粒细胞氧化爆发活性在干细胞移植后没有明显变化。CD14+CD16+单核细胞数量重建分析显示与慢性 GVHD发生率降低有潜在相关性。

结论

异基因 PBSCT 后早期中性粒细胞和单核细胞的功能恢复不仅在吞噬作用和氧化爆发方面存在差异,而且在刺激物和分析氧化爆发活性的细胞群体方面也存在差异。CD16+CD14+单核细胞亚群可能是慢性 GVHD风险降低的预测因子。

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