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肺移植受者中性粒细胞动态亚群及其功能:一项为期一年的纵向初步研究的见解

Dynamic Neutrophil Subsets and Function in Lung Transplant Recipients: Insights from a One-Year Longitudinal Pilot Study.

作者信息

Kaisar-Iluz Naomi, Shaul Merav E, Deri Ofir, Huszti Ella, Peled Michael, Bezalel Yael, Fridlender Zvi G, Levy Liran

机构信息

Hadassah Medical Center, Institute of Pulmonary Medicine, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.

Sheba Lung Transplant Program, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel.

出版信息

J Clin Med. 2025 Apr 13;14(8):2660. doi: 10.3390/jcm14082660.

Abstract

: Neutrophils are key innate immune cells in peripheral blood. In recent years, sub-populations of neutrophils have been identified. In addition to the normal-density neutrophils (NDNs) in both healthy subjects and patients, low-density neutrophils (LDNs) were described in chronic inflammation and cancer. In lung transplants (LTx), neutrophils play crucial roles in reperfusion injury, acute rejection, and chronic lung allograft dysfunction. Our pilot study examines neutrophil subsets and function in LTx recipients during the first post-transplant year. : We collected blood from 11 LTx recipients at various intervals. LDNs and normal-density neutrophils (NDNs) were isolated. The production of reactive oxygen species (ROS) by NDNs was measured after PMA activation using a Luminol-HRP assay. Neutrophil phenotypic markers were analyzed with flow cytometry. : The LDN-to-NDN ratio increased at 3 and 6 months post-transplant. Expression levels of CD62-L (aging marker), PDL-1 (immune checkpoint), CD15 (maturation), and CXCR4 (homeostasis regulator) showed modulation. Interestingly, ROS production by NDNs was mildly elevated at baseline, reduced at 6 months, and returned to baseline levels by 9 months post-transplant. : Neutrophils exhibit dynamic changes in the first post-LTx year. Investigating neutrophil plasticity could reveal clinically relevant biomarkers and facilitate the development of diagnostic and therapeutic tools in LTx.

摘要

中性粒细胞是外周血中的关键固有免疫细胞。近年来,已鉴定出中性粒细胞的亚群。除了健康受试者和患者体内的正常密度中性粒细胞(NDNs)外,在慢性炎症和癌症中还发现了低密度中性粒细胞(LDNs)。在肺移植(LTx)中,中性粒细胞在再灌注损伤、急性排斥反应和慢性肺移植功能障碍中起关键作用。我们的初步研究考察了LTx受者移植后第一年中性粒细胞亚群及其功能。

我们在不同时间点采集了11名LTx受者的血液。分离出LDNs和正常密度中性粒细胞(NDNs)。使用鲁米诺 - 辣根过氧化物酶测定法在佛波酯(PMA)激活后测量NDNs产生活性氧(ROS)的情况。用流式细胞术分析中性粒细胞表型标志物。

移植后3个月和6个月时,LDN与NDN的比例增加。CD62 - L(衰老标志物)、程序性死亡受体1(PDL - 1)(免疫检查点)、CD15(成熟度)和CXC趋化因子受体4(CXCR4)(稳态调节因子)的表达水平出现了变化。有趣的是,NDNs产生ROS的水平在基线时略有升高,在6个月时降低,移植后9个月恢复到基线水平。

中性粒细胞在LTx后的第一年表现出动态变化。研究中性粒细胞的可塑性可能会揭示临床相关的生物标志物,并促进LTx诊断和治疗工具的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16e7/12028280/427021818d90/jcm-14-02660-g001.jpg

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