新型冠状病毒刺突蛋白对单核巨噬细胞分泌炎症因子的 影响

doi:10.19871/j.cnki.xfcrbzz.2023.03.007

摘要/Abstract

摘要： 目的探讨SARS-CoV-2对单核巨噬细胞分泌炎症因子的作用及机制。方法纳入石家庄市第五医院2020年1月21日至2月10日以及2021年1月3日至1月7日住院的COVID-19确诊患者（病例组）与健康对照者（对照组）各53例,收集病例资料与血常规检测结果。采用SARS-CoV-2刺突蛋白刺激单核巨噬细胞,细胞增殖-毒性检测细胞活力,荧光定量PCR法检测炎症因子IL-6、IL-1β和CCL2与信号通路分子JAK1、STAT1和NF-κB的表达。结果 COVID-19患者的单核细胞比值与中性粒细胞比值高于对照组,而淋巴细胞比值、淋巴细胞计数、嗜酸性粒细胞比值、嗜酸性粒细胞计数与红细胞压积低于对照组。SARS-CoV-2刺突蛋白刺激单核巨噬细胞后,在100ng/ml与300ng/ml的浓度下细胞活力高于对照组（P=0.046）,在浓度为500ng/ml时IL-6、IL-1β与CCL2的mRNA表达含量最高（P<0.01,P=0.036,P<0.001）,在浓度100ng/ml时JAK1与STAT1的mRNA表达明显升高（P<0.001）,在300ng/ml与500ng/ml刺激下,NF-κB表达增高（P<0.001）。结论 COVID-19患者的单核细胞升高,SARS-CoV-2刺突蛋白可能通过JAK1/STAT1信号通路促进单核巨噬细胞分泌炎症因子,在细胞因子风暴中发挥作用。

关键词: 新型冠状病毒, 刺突蛋白, 单核巨噬细胞, 炎症因子, 细胞因子风暴, 信号通路

Abstract: Objective The aim of this study was to investigate the role and mechanism of SARS-CoV-2 virus on the secretion of inflammatory factors by mononuclear macrophages. Method Fifty-three patients with confirmed COVID-19 hospitalized from January 21 to February 10, 2020 and January 3 to January 7, 2021 were selected from Shijiazhuang Fifth Hospital, fifty-three healthy controls each were included, and the results of medical records and routine blood test were collected. Mononuclear macrophages were stimulated with SARS-CoV-2 virus spiked protein, cell viability was detected by CCK-8 assay. The level of pro-inflammatory cytokines IL-6, IL-1β and CCL2 and the expression of signaling pathway molecules JAK1, STAT1 and NF-κB were detected by quantitative RT-PCR. Result The monocyte ratio and neutrophil ratio were higher, while the lymphocyte ratio, lymphocyte count, eosinophil ratio, and eosinophil count, and hematocrit were lower in COVID-19 patients than those in controls. After stimulation of mononuclear macrophages by SARS-CoV-2 virus spiked protein, cell viability was higher at concentrations of 100ng/ml and 300ng/ml (P=0.046). The highest mRNA expression levels of IL-6, IL-1β and CCL2 at a concentration of 500ng/ml (P<0.01, P=0.036, P<0.001). The expression of JAK1 and STAT1 at a concentration of 100ng/ml (P<0.001), the expression of NF-κB expression was increased at 300 and 500ng/ml stimulation (P<0.001). Conclusion SARS-CoV-2 viral spike protein may promote inflammatory cytokine secretion by mononuclear macrophages through the JAK1/STAT1 signaling pathway, which play a role in the cytokine storm.

Key words: Severe acute respiratory syndrome coronavirus 2, Spike protein, Mononuclear macrophages, Inflammatory cytokine, Cytokine storm, Signal pathway

中图分类号:

R512.99

丁芳, 江平, 李力, 张鑫, 戴二黑, 闫会敏. 新型冠状病毒刺突蛋白对单核巨噬细胞分泌炎症因子的影响[J]. 新发传染病电子杂志, 2023, 8(3): 34-38.

Ding Fang, Jiang Ping, Li Li, Zhang Xin, Dai Erhei, Yan Huimin. Effect of novel coronavirus spike protein on the secretion of inflammatory factors by mononuclear macrophages[J]. Electronic Journal of Emerging Infectious Diseases, 2023, 8(3): 34-38.

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