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镰状细胞病中性粒细胞表型与功能的动态变化

Dynamics of neutrophil phenotype and function in sickle cell disease.

作者信息

Gaartman Aafke E, de Ligt Lydian A, Beuger Boukje M, Tool Anton T J, Veldthuis Martijn, Kuijpers Taco W, van Zwieten Rob, Biemond Bart J, van Bruggen Robin, Nur Erfan

机构信息

Department of Hematology, Amsterdam University Medical Center, Amsterdam, Netherlands.

Red Cell Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands.

出版信息

Front Immunol. 2025 May 2;16:1591283. doi: 10.3389/fimmu.2025.1591283. eCollection 2025.

DOI:10.3389/fimmu.2025.1591283
PMID:40386776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12081264/
Abstract

INTRODUCTION

While sickle cell disease (SCD) is primarily acknowledged as an erythrocyte disorder, emerging evidence suggests a role for altered neutrophil phenotype and function in SCD pathophysiology and disease severity. Given the conflicting findings in previous studies, we performed a comprehensive exploration of neutrophil characteristics in SCD patients during steady state and vaso-occlusive crisis (VOC), as well as in response to therapeutic interventions.

METHODS

Neutrophil phenotype was assessed by flow cytometry and functional properties were evaluated by measurement of neutrophil adhesion and reactive oxygen species (ROS) production.

RESULTS

A total of 49 SCD patients (of whom 19 during both steady state and VOC) along with 16 healthy ethnicity-matched and 30 non-matched controls, were included in the study. Differences were observed between neutrophils from patients compared to controls and between control groups. Neutrophil phenotype was more activated in SCD patients compared to non-matched controls. Neutrophil adhesion was increased in steady-state SCD patients compared to both ethnicity-matched and non-matched controls.

DISCUSSION

While neutrophil phenotype in SCD patients differed from non-matched controls, in contrast to earlier studies, the differences in neutrophil phenotype between SCD patients and ethnicity-matched controls were modest. neutrophil adhesion was higher in SCD patients than in ethnicity-matched and non-matched controls. Potential explanations for the discrepancies between earlier findings and our study are the large variation in neutrophil phenotypes between individuals, methodological variability between studies and differences in the time interval between blood sample collection and the measurements.

摘要

引言

虽然镰状细胞病(SCD)主要被认为是一种红细胞疾病,但新出现的证据表明,中性粒细胞表型和功能的改变在SCD病理生理学和疾病严重程度中起作用。鉴于先前研究结果相互矛盾,我们对SCD患者在稳态和血管闭塞性危机(VOC)期间的中性粒细胞特征进行了全面探索,并研究了其对治疗干预的反应。

方法

通过流式细胞术评估中性粒细胞表型,并通过测量中性粒细胞黏附和活性氧(ROS)生成来功能特性。

结果

本研究共纳入49例SCD患者(其中19例在稳态和VOC期间均参与),以及16例种族匹配的健康对照和30例非匹配对照。观察到患者中性粒细胞与对照之间以及对照组之间存在差异。与非匹配对照相比,SCD患者的中性粒细胞表型更活跃。与种族匹配和非匹配对照相比,稳态SCD患者的中性粒细胞黏附增加。

讨论

虽然SCD患者的中性粒细胞表型与非匹配对照不同,但与早期研究相比,SCD患者与种族匹配对照之间的中性粒细胞表型差异较小。SCD患者的中性粒细胞黏附高于种族匹配和非匹配对照。早期研究结果与我们的研究之间差异的潜在解释包括个体间中性粒细胞表型的巨大差异、研究间方法学的变异性以及血样采集与测量之间时间间隔的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c10/12081264/9c8ee9874240/fimmu-16-1591283-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c10/12081264/80cc50fbc643/fimmu-16-1591283-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c10/12081264/9c8ee9874240/fimmu-16-1591283-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c10/12081264/80cc50fbc643/fimmu-16-1591283-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c10/12081264/9c8ee9874240/fimmu-16-1591283-g002.jpg

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Liver-to-lung microembolic NETs promote gasdermin D-dependent inflammatory lung injury in sickle cell disease.
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