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颗粒洞察:儿科队列中严重哮喘加重时的中性粒细胞优势和弹性蛋白酶释放。

Granular Insights: Neutrophil Predominance and Elastase Release in Severe Asthma Exacerbations in a Pediatric Cohort.

机构信息

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

出版信息

Cells. 2024 Mar 18;13(6):533. doi: 10.3390/cells13060533.

DOI:10.3390/cells13060533
PMID:38534377
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10969278/
Abstract

The chronic inflammatory component of asthma is propagated by granulocytes, including neutrophils and eosinophils, in the peripheral circulation and airway. Previous studies have suggested that these cells have an altered expression of adhesion-related molecules and a propensity for the release of granule contents that may contribute to tissue damage and enhance inflammatory complications in patients with status asthmaticus. The goal of this prospective cohort study at a tertiary care pediatric hospital with a large population of asthma patients was to assess the role of granulocyte-based inflammation in the development of asthma exacerbation. Subjects were enrolled from two patient populations: those with mild-to-moderate asthma exacerbations seen in the emergency department and those with severe asthma admitted to the intensive care unit (PICU). Clinical data were collected, and blood was drawn. Granulocytes were immediately purified, and the phenotype was assessed, including the expression of cell surface markers, elastase release, and cytokine production. Severe asthmatics admitted to the PICU displayed a significantly higher total neutrophil count when compared with healthy donors. Moreover, little to no eosinophils were found in granulocyte preparations from severe asthmatics. Circulating neutrophils from severe asthmatics admitted to the PICU displayed significantly increased elastase release ex vivo when compared with the PMN from healthy donors. These data suggest that the neutrophil-based activation and release of inflammatory products displayed by severe asthmatics may contribute to the propagation of asthma exacerbations.

摘要

哮喘的慢性炎症成分由外周循环和气道中的粒细胞(包括中性粒细胞和嗜酸性粒细胞)传播。先前的研究表明,这些细胞的粘附相关分子表达发生改变,并且有释放颗粒内容物的倾向,这可能导致组织损伤,并增强哮喘持续状态患者的炎症并发症。这项在一家拥有大量哮喘患者的三级保健儿科医院进行的前瞻性队列研究的目的是评估基于粒细胞的炎症在哮喘恶化中的作用。受试者来自两个患者群体:在急诊科就诊的轻度至中度哮喘恶化患者和入住重症监护病房(PICU)的严重哮喘患者。收集临床数据并抽取血液。立即纯化粒细胞,并评估其表型,包括细胞表面标志物的表达、弹性蛋白酶释放和细胞因子产生。与健康供体相比,入住 PICU 的严重哮喘患者的总中性粒细胞计数明显更高。此外,在严重哮喘患者的粒细胞制剂中几乎没有发现嗜酸性粒细胞。与健康供体的 PMN 相比,入住 PICU 的严重哮喘患者的循环中性粒细胞显示出明显增加的弹性蛋白酶体外释放。这些数据表明,严重哮喘患者表现出的基于中性粒细胞的激活和炎症产物的释放可能有助于哮喘恶化的传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/6ea2fdc25d54/cells-13-00533-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/9fe48f5e5630/cells-13-00533-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/39af16b82d9a/cells-13-00533-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/c0045dd16389/cells-13-00533-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/56f068e6f51f/cells-13-00533-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/6ea2fdc25d54/cells-13-00533-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/9fe48f5e5630/cells-13-00533-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/39af16b82d9a/cells-13-00533-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/c0045dd16389/cells-13-00533-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/56f068e6f51f/cells-13-00533-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d07/10969278/6ea2fdc25d54/cells-13-00533-g005.jpg

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