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中性粒细胞胞外陷阱在小儿炎症性肠病中的作用:溃疡性结肠炎的潜在作用。

Neutrophil Extracellular Traps in Pediatric Inflammatory Bowel Disease: A Potential Role in Ulcerative Colitis.

机构信息

Pediatric Hemato-Oncology Research Laboratory, Tel Aviv Medical Center, Tel Aviv 6423906, Israel.

Department of Pediatric Hemato-Oncology, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel.

出版信息

Int J Mol Sci. 2024 Oct 16;25(20):11126. doi: 10.3390/ijms252011126.


DOI:10.3390/ijms252011126
PMID:39456908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11507660/
Abstract

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gut affecting both adults and children. Neutrophil extracellular traps (NETs) are structures released by activated neutrophils, potentially contributing to tissue damage in various diseases. This study aimed to explore the presence and role of NETs in pediatric IBD. We compared intestinal biopsies and peripheral blood from 20 pediatric IBD patients (UC and CD) to controls. Biopsy staining and techniques for neutrophil activation were used to assess neutrophil infiltration and NET formation. We also measured the enzymatic activity of key NET proteins and evaluated NET formation in UC patients in remission. Both UC and CD biopsies showed significantly higher levels of neutrophils and NETs compared to controls ( < 0.01), with UC exhibiting the strongest association. Peripheral blood neutrophils from UC patients at diagnosis displayed increased NET formation compared to controls and CD patients. Interestingly, NET formation normalized in UC patients following remission-inducing treatment. This pilot study suggests a potential role for NETs in pediatric IBD, particularly UC. These findings warrant further investigation into the mechanisms of NET involvement and the potential for targeting NET formation as a therapeutic strategy.

摘要

炎症性肠病(IBD)包括克罗恩病(CD)和溃疡性结肠炎(UC),是一种影响成人和儿童的肠道慢性炎症性疾病。中性粒细胞胞外陷阱(NETs)是活化中性粒细胞释放的结构,可能与各种疾病中的组织损伤有关。本研究旨在探讨 NETs 在儿科 IBD 中的存在和作用。我们比较了 20 名儿科 IBD 患者(UC 和 CD)和对照组的肠道活检和外周血。使用活检染色和中性粒细胞活化技术评估中性粒细胞浸润和 NET 形成。我们还测量了关键 NET 蛋白的酶活性,并评估了缓解期 UC 患者的 NET 形成。与对照组相比,UC 和 CD 活检均显示中性粒细胞和 NETs 水平显著升高(<0.01),UC 相关性最强。UC 患者在诊断时的外周血中性粒细胞与对照组和 CD 患者相比,NET 形成增加。有趣的是,UC 患者在缓解诱导治疗后 NET 形成正常化。这项初步研究表明 NETs 在儿科 IBD 中具有潜在作用,特别是 UC。这些发现需要进一步研究 NET 参与的机制以及将 NET 形成作为治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/8b0e72eeb4bc/ijms-25-11126-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/3bb281bffadc/ijms-25-11126-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/644712db8d48/ijms-25-11126-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/4ed74a4ae273/ijms-25-11126-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/6821a1ed0311/ijms-25-11126-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/8b0e72eeb4bc/ijms-25-11126-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/3bb281bffadc/ijms-25-11126-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/644712db8d48/ijms-25-11126-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/4ed74a4ae273/ijms-25-11126-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/6821a1ed0311/ijms-25-11126-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/930c/11507660/8b0e72eeb4bc/ijms-25-11126-g005.jpg

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引用本文的文献

[1]
Neutrophil Extracellular Traps (NETs) in Immunity and Diseases: Second Edition.

Int J Mol Sci. 2025-7-8

本文引用的文献

[1]
Methods for the Assessment of NET Formation: From Neutrophil Biology to Translational Research.

Int J Mol Sci. 2022-12-13

[2]
Histone H3 clipping is a novel signature of human neutrophil extracellular traps.

Elife. 2022-10-25

[3]
Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease.

Life (Basel). 2021-12-10

[4]
Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results.

J Can Assoc Gastroenterol. 2020-3-27

[5]
Paediatric Inflammatory Bowel Disease and its Relationship with the Microbiome.

Microb Ecol. 2021-11

[6]
Histones, DNA, and Citrullination Promote Neutrophil Extracellular Trap Inflammation by Regulating the Localization and Activation of TLR4.

Cell Rep. 2020-5-5

[7]
Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Responses.

Cells. 2020-4-8

[8]
Neutrophil Elastase Activity as a Surrogate Marker for Neutrophil Extracellular Trap Formation following Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant. 2019-8-5

[9]
Neutrophil Extracellular Traps Induce Intestinal Damage and Thrombotic Tendency in Inflammatory Bowel Disease.

J Crohns Colitis. 2020-2-10

[10]
Neutrophil Extracellular Traps.

Methods Mol Biol. 2019

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