Department of Pathology, Saint Louis University, St. Louis, MO 63104, USA.
Department of Internal Medicine, Saint Louis University, St. Louis, MO 63104, USA.
Int J Mol Sci. 2021 Mar 20;22(6):3184. doi: 10.3390/ijms22063184.
SARS-CoV-2 infection can cause cytokine storm and may overshoot immunity in humans; however, it remains to be determined whether virus-induced soluble mediators from infected cells are carried by exosomes as vehicles to distant organs and cause tissue damage in COVID-19 patients. We took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and COVID-19 patients. Our results revealed that tenascin-C (TNC) and fibrinogen-β (FGB) are highly abundant in exosomes from COVID-19 patients' plasma compared with that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via the Nuclear factor-κB (NF-κB) pathway, we examined the status of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-C motif chemokine ligand 5 (CCL5) expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase compared with that from healthy subjects. Together, our results demonstrate that TNC and FGB are transported through plasma exosomes and potentially trigger pro-inflammatory cytokine signaling in cells of distant organ.
SARS-CoV-2 感染可引起细胞因子风暴，并可能导致人类免疫过度；然而，仍需确定感染细胞产生的病毒诱导的可溶性介质是否作为载体通过外泌体被携带到远处器官，并在 COVID-19 患者中引起组织损伤。我们采用无偏蛋白组学方法分析了来自健康志愿者和 COVID-19 患者血浆的外泌体。我们的结果表明，与健康正常对照组相比，COVID-19 患者血浆中外泌体中的 tenascin-C（TNC）和纤维蛋白原-β（FGB）含量非常高。由于 TNC 和 FGB 通过核因子-κB（NF-κB）途径刺激促炎细胞因子，我们研究了暴露于 COVID-19 患者外泌体的肝细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和 C-C 基序趋化因子配体 5（CCL5）表达的状态，并观察到与健康供体相比明显增加。总之，我们的结果表明 TNC 和 FGB 通过血浆外泌体运输，并可能在远处器官的细胞中触发促炎细胞因子信号转导。
