Impaired Degradation of Neutrophil Extracellular Traps: A Possible Severity Factor of Elderly Male COVID-19 Patients.

Impaired Degradation of Neutrophil Extracellular Traps: A Possible Severity Factor of Elderly Male COVID-19 Patients.
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DOI:
10.1159/000521594
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发表时间:
2022
影响因子:
5.3
通讯作者:
--
中科院分区:
医学2区
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--
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中性粒细胞细胞外陷阱(NETs)被描述为严重COVID-19的潜在触发因素。NETs被称为细胞外DNA纤维,由中性粒细胞在感染反应中释放。如果宿主不能平衡休眠酶(dnase)对net的有效清除,就会发生有害的后果。COVID-19患者中NETs水平升高与发病血栓性并发症的高风险相关。在这里,我们研究了与健康对照组相比,一组COVID-19患者的NET标记物水平和dna酶活性。我们的数据证实,COVID-19患者血浆中NET标志物水平升高,且男性高于女性。与此同时,与健康对照组相比,在COVID-19患者中检测到的dna酶活性增加。重要的是,dna酶活性与男性患者的年龄呈负相关。抗微生物肽LL-37被认为可以稳定NETs,防止dna酶降解,在严重急性呼吸综合征冠状病毒2型感染后,它被嵌入NETs中。男性COVID-19患者血浆LL-37水平与net标志物水平相关,提示LL-37可能通过稳定net抗dna酶降解作用,在男性COVID-19患者net相关血栓形成风险中发挥潜在作用。总之,我们的数据确定了老年男性患者的两个潜在危险因素:DNase活性降低和LL-37水平升高,这可能导致COVID-19期间NET降解效率低下,从而导致NET相关血栓形成的风险增加。
Neutrophil extracellular traps (NETs) have been described as a potential trigger of severe COVID-19. NETs are known as extracellular DNA fibers released by neutrophils in response to infection. If the host is unable to balance efficient clearance of NETs by dornases (DNases), detrimental consequences occur. Elevated levels of NETs in COVID-19 patients are associated with higher risk of morbid thrombotic complications. Here, we studied the level of NET markers and DNase activity in a cohort of COVID-19 patients compared to healthy controls. Our data confirmed an increased level of NET markers in the plasma of COVID-19 patients, with a higher level in male compared to female patients. At the same time, there was an increased DNase activity detectable in COVID-19 patients compared to healthy controls. Importantly, there was a negative correlation of DNase activity with the age of male patients. The antimicrobial peptide LL-37, which is known to stabilize NETs against DNase degradation, is embedded in NETs upon severe acute respiratory syndrome coronavirus-2-infection. The LL-37 plasma level correlates with the NET-marker level in male COVID-19 patients, indicating a potential role of LL-37 in the risk of NET-associated thrombosis in male COVID-19 patients by stabilizing NETs against DNase degradation. In conclusion, our data identify two potential risk factors of elderly male patients which may lead to inefficient NET degradation and a subsequently higher risk of NET-associated thrombosis during COVID-19: reduced DNase activity and an increased LL-37 level.
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