Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA.
Center for Life Sciences, Mahindra University, Hyderabad, India.
Virulence. 2023 Dec;14(1):2218077. doi: 10.1080/21505594.2023.2218077.
Neutrophil dysregulation is well established in COVID-19. However, factors contributing to neutrophil activation in COVID-19 are not clear. We assessed if N-formyl methionine (fMet) contributes to neutrophil activation in COVID-19. Elevated levels of calprotectin, neutrophil extracellular traps (NETs) and fMet were observed in COVID-19 patients ( = 68), particularly in critically ill patients, as compared to HC ( = 19, < 0.0001). Of note, the levels of NETs were higher in ICU patients with COVID-19 than in ICU patients without COVID-19 ( < 0.05), suggesting a prominent contribution of NETs in COVID-19. Additionally, plasma from COVID-19 patients with mild and moderate/severe symptoms induced in vitro neutrophil activation through fMet/FPR1 (formyl peptide receptor-1) dependent mechanisms ( < 0.0001). fMet levels correlated with calprotectin levels validating fMet-mediated neutrophil activation in COVID-19 patients ( = 0.60, = 0.0007). Our data indicate that fMet is an important factor contributing to neutrophil activation in COVID-19 disease and may represent a potential target for therapeutic intervention.
中性粒细胞失调在 COVID-19 中已得到充分证实。然而，导致 COVID-19 中性粒细胞活化的因素尚不清楚。我们评估了 N-甲酰基甲硫氨酸 (fMet) 是否会导致 COVID-19 中的中性粒细胞活化。与 HC（ = 19， < 0.0001）相比，COVID-19 患者（ = 68），尤其是重症患者，观察到钙卫蛋白、中性粒细胞胞外陷阱 (NETs) 和 fMet 水平升高。值得注意的是，COVID-19 重症监护病房患者的 NETs 水平高于无 COVID-19 的重症监护病房患者（ < 0.05），表明 NETs 在 COVID-19 中发挥了重要作用。此外，来自 COVID-19 轻症和中重度/严重症状患者的血浆通过 fMet/FPR1（甲酰肽受体-1）依赖机制在体外诱导中性粒细胞活化（ < 0.0001）。fMet 水平与钙卫蛋白水平相关，验证了 COVID-19 患者中 fMet 介导的中性粒细胞活化（ = 0.60， = 0.0007）。我们的数据表明，fMet 是导致 COVID-19 疾病中性粒细胞活化的重要因素，可能代表治疗干预的潜在靶点。
