血小板12-氧酶的缺乏会在SARS-CoV-2感染期间加剧炎症和疾病严重程度
Ana Claudia Dos S P Andrade1, Emile Lacasse1, Isabelle Dubuc1
1Division of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
概括
血小板12-lipoxygenase (12-LOX) 缺乏在SARS-CoV-2感染中加剧肺炎和死亡率,揭示了其在宿主防御中的关键作用,并建议新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 病毒学 病毒学
背景情况:
- 血小板对于静血和免疫反应至关重要.
- 在严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 感染期间,血小板过度活化,释放炎症媒介.
- 血小板12-氧酶 (12-LOX) 在SARS-CoV-2病变发生中的特定作用尚不清楚.
研究的目的:
- 研究血小板12-氧酶 (12-LOX) 在宿主对SARS-CoV-2感染的反应中的作用.
- 阐明12-LOX缺乏对肺炎,免疫细胞透和在SARS-CoV-2感染期间宿主生存的影响.
主要方法:
- 使用了缺乏血小板12-LOX.的小鼠.
- 进行了肺组织的组织病理学分析.
- 进行了转录组和脂组分析 (质谱学).
- 评估白细胞透,细胞因子生产,发病率和生存率.
主要成果:
- 与野生型小鼠相比,12-LOX缺乏小鼠的SARS-CoV-2感染导致肺炎,白细胞透和细胞因子产生增加.
- 观察到明显的血小板和肺部转录变化,包括改变的NLRP1炎症酶基因表达.
- 脂质组分析显示,缺乏12-HETrE的小鼠的12-HETrE水平降低,与疾病严重程度相反相关.
- 血小板12-LOX缺乏导致发病率增加和生存率降低.
结论:
- 血小板12-LOX在缓解肺炎和改善在SARS-CoV-2感染期间的存活率方面发挥着保护作用.
- 12-LOX介导的脂质代谢与COVID-19中的炎症反应和炎症酶激活密切相关.
- 针对血小板12-LOX通路可能为严重的COVID-19提供新的治疗策略.
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