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中性粒细胞胞外诱捕网在新型冠状病毒肺炎发病机制中的作用

Implication of Neutrophils Extracellular Traps in the Pathogenesis of SARS-CoV-2 pneumonia.

作者信息

Pérez-Guerrero Patricia, Illanes-Álvarez Francisco, Márquez-Ruiz Denisse, Campaña-Gómez Irene, Cuesta-Sancho Sara, Márquez-Coello Mercedes, Girón-González José-Antonio

机构信息

Servicio de Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto para la Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain.

Departamento de Inmunología, Facultad de Medicina, Universidad de Valladolid, 47003 Valladolid, Spain.

出版信息

Biomedicines. 2022 Oct 20;10(10):2638. doi: 10.3390/biomedicines10102638.

Abstract

Peripheral blood polymorphonuclear neutrophils (PMNs) forming extracellular traps (NETs), as well as endothelial- and platelet-derived parameters, have been analyzed in patients with SARS-CoV-2 pneumonia, and their prognostic role has been evaluated. Eighty-seven consecutive patients hospitalized with SARS-CoV-2 pneumonia were prospectively selected. A sample of 30 healthy individuals served as the control group. Clinical and oxygenation (oxygen saturation to fraction of inspired oxygen ratio-SpO/FiO) characteristics and PMNs forming NETs, serum levels of myeloperoxidase, E-selectin, vascular cell adhesion molecule 1-VCAM1-vascular endothelial growth factor, P-selectin, platelet factor 4 and plasma concentrations of D-dimer were evaluated at hospital admission, at discharge and 14 days after discharge. Intensive care unit admission or death was the primary composite endpoint. Patients showed a higher number of PMNs forming NETs than healthy controls. The absolute number of PMNs forming NETs was inversely correlated with oxygen status (SpO/FiO) and positively with inflammatory (C-reactive protein, ferritin) markers and VCAM1. A decrease in, but not a normalization of NETs and endothelial-derived parameters was observed in patients who survived. In conclusion, the formation of NETs runs parallel to that of other inflammatory and endothelial activation markers, and is inverse to the oxygenation parameters, supporting a pathogenic role for PMNs in this entity.

摘要

在新型冠状病毒肺炎患者中,对形成细胞外陷阱(NETs)的外周血多形核中性粒细胞(PMN)以及内皮细胞和血小板衍生参数进行了分析,并评估了它们的预后作用。前瞻性选取了87例因新型冠状病毒肺炎住院的连续患者。30名健康个体的样本作为对照组。在入院时、出院时和出院后14天评估临床和氧合(氧饱和度与吸入氧分数之比-SpO₂/FiO₂)特征以及形成NETs的PMN、髓过氧化物酶、E-选择素、血管细胞黏附分子1(VCAM1)、血管内皮生长因子、P-选择素、血小板因子4的血清水平和D-二聚体的血浆浓度。入住重症监护病房或死亡是主要的复合终点。患者中形成NETs的PMN数量高于健康对照组。形成NETs的PMN绝对数量与氧状态(SpO₂/FiO₂)呈负相关,与炎症(C反应蛋白、铁蛋白)标志物和VCAM1呈正相关。存活患者的NETs和内皮衍生参数有所下降,但未恢复正常。总之,NETs的形成与其他炎症和内皮激活标志物的形成平行,且与氧合参数相反,支持PMN在该疾病中的致病作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b4/9599188/854bb7cb0dc8/biomedicines-10-02638-g001.jpg

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