Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies.
Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies.
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DOI：
10.3390/ijms232113033
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发表时间：
2022-10-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
炎性小体复合体是慢性疾病和急性感染的关键部分，负责细胞因子的释放和细胞死亡机制的调节。SARS-CoV-2感染的特征是细胞因子释放失调。在这种情况下，SARS-CoV-2感染中的炎性小体复合物分析可能有助于了解疾病的机制。对死于COVID-19的患者（n = 24）进行了死后微创尸检，并将肺部样本与患者对照组（n = 11）和2009年大流行的甲型流感病毒H1N1亚型组（n = 10）进行了比较。使用苏木精-伊红染色进行组织学分析。使用针对以下靶标的单克隆抗体进行免疫组织化学（IHC）染色：ACE 2、TLR 4、NF-κB、NLRP-3（或NALP）、IL-1β、IL-18、ASC、CASP 1、CASP 9、GSDMD、NOX 4、TNF-α。从数字分析中获得的数据进行了适当的统计检验。IHC分析显示，COVID-19组中指示炎性小体激活的生物标志物（ACE 2; NF-κB; NOX 4; ASC）显著增加（所有p < 0.05），并且指示细胞焦亡和炎性小体衍生的细胞因子（如IL-18（p < 0.005）和CASP 1）的生物标志物大大增加（p < 0.0001），即使与H1N1组相比。我们认为SARS-CoV-2的发病机制与炎性小体复合物的激活有关。进一步的研究仍然是必要的，以阐明疾病的病理生理。
The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease’s mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1β, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.
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