Role of LL-37 in thrombotic complications in patients with COVID-19.
Role of LL-37 in thrombotic complications in patients with COVID-19.
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DOI：
10.1007/s00018-022-04309-y
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发表时间：
2022-05-21
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凝血功能障碍引起的血凝块形成是2019冠状病毒病（COVID-19）的常见并发症，也是重症和死亡的高危因素。神经细胞外陷阱（NET）与COVID-19诱导的免疫血栓形成有关。此外，NET成分人cathelicidin可以干扰SARS-CoV-2刺突蛋白与其ACE 2受体之间的相互作用，该受体介导病毒进入细胞。但目前，SARS-CoV-2感染后凯萨林菌素抗菌肽的水平及其在COVID-19血栓形成中的作用尚不清楚。在当前的研究中，我们分析了凝血功能，发现COVID-19患者的凝血酶时间减少，但纤维蛋白原水平、凝血酶原时间和活化部分凝血活酶时间增加。此外，cathelicidin抗菌肽LL-37被刺突蛋白上调，并在患者血浆中显著升高。此外，LL-37水平与凝血酶时间呈负相关，而与纤维蛋白原水平呈正相关。除了血小板活化之外，凯萨林菌素肽增强凝血因子如因子Xa（FXa）和凝血酶的活性，这可能在具有高凯萨林菌素肽水平的疾病中诱导高凝血。注射cathelicidin肽促进血栓形成，而删除cathelicidin抑制体内血栓形成。这些结果表明，cathelicidin抗菌肽LL-37在SARS-CoV-2感染过程中升高，可能通过激活凝血因子诱导COVID-19患者高凝状态。在线版本包含补充材料，可通过10.1007/s 00018 -022-04309-y获得。
Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors. The online version contains supplementary material available at 10.1007/s00018-022-04309-y.
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