激发性和炎症介质由两极化的M1和M2巨细胞产生,这些巨细胞被D-二聚体和SARS-CoV-2尖峰免疫复合体激活
Yun-Jong Park1, David Acosta2, Mohammad Rubel Hoq2
1Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA; Division of Hemostasis, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, USA.
Cytokine
|December 2, 2023
概括
免疫复合体 (IC) 与SARS-CoV-2尖端蛋白和D-二次体 (DD) 触发肺巨细胞的炎症反应. 这种相互作用,特别是与M1巨细胞的相互作用,表明一种机制导致严重的COVID-19炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 病理学 病理学 病理学
背景情况:
- 肺部巨细胞在对抗SARS-CoV-2的宿主防御中至关重要,但在严重的COVID-19中可能导致超级炎症.
- 凝血病,以D-二次体 (DD) 升高表示,在严重的COVID-19中很常见.
- 涉及病毒抗原的免疫复合体 (IC) 可能会加剧炎症反应.
研究的目的:
- 调查SARS-CoV-2尖端特异性免疫复合体 (IC) 是否会在人类肺部巨细胞中触发异常细胞因子的产生.
- 确定D-二聚体 (DD) 在调节这些巨细胞反应中的作用.
- 为了比较不同巨细胞极化状态 (M0,M1,M2) 的反应.
主要方法:
- 使用人类M0,M1和M2极化巨细胞.
- 刺激的巨细胞与SARS-CoV-2重组S蛋白或伪病毒的IC.
- 与D-二元体 (DD) 和IC共同刺激的巨细胞,评估细胞因子的产生 (PGE2,IL-6,TNFα,IL-1β,IL-10).
主要成果:
- 在所有巨细胞子集中,D-二聚体 (DD) 对于IC诱导的前列腺素E2 (PGE2) 生产至关重要.
- 在M1巨细胞 (M1≫M2>M0) 中,PGE2水平最高,与尖端结合抗体相关.
- 所有子集都产生IL-6,而TNFα,IL-1β和IL-10在DD+IC刺激时由M2巨细胞产生.
结论:
- 与D-二元体 (DD) 结合的SARS-CoV-2 IC可以促进肺组织中的炎症性巨细胞反应.
- 这种相互作用可能会导致在严重的COVID-19中观察到的超炎症状态.
- 增加的尖端结合抗体和凝血副产品可能导致严重的COVID-19病原体.
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