Frontiers in Immunology (Oct 2021)

Effects of Neutrophil Extracellular Traps in Patients With Septic Coagulopathy and Their Interaction With Autophagy

  • Jia-Yu Mao,
  • Jia-Hui Zhang,
  • Wei Cheng,
  • Jian-Wei Chen,
  • Na Cui

DOI
https://doi.org/10.3389/fimmu.2021.757041
Journal volume & issue
Vol. 12

Abstract

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IntroductionNeutrophil extracellular traps (NETs) act as a critical trigger of inflammation and coagulation. We hypothesized that NETs are associated with septic hypercoagulability.Materials and MethodsIn total, 82 patients admitted with sepsis in the Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled between February 2017 and April 2018. Clinical and hematological parameters and thrombotic or hemorrhagic events were recorded. Blood samples were obtained to assess biomarkers of NET formation, including neutrophil elastase 2 (ELA2) and citrullinated histone H3, and endothelial-derived biomarker syndecan-1. Autophagy levels and their regulation pathway were also examined to explore their interaction with NETs.ResultSepsis patients with disseminated intravascular coagulation (DIC) showed significantly higher levels of NET formation [ELA2, 1,247 (86–625) vs. 2,039 (1,544–2,534), p < 0.0001; H3, 140 (47–233) vs. 307 (199–415), p < 0.0001]. NET formation was independently associated with DIC risk [ELA2, OR 1.0028, 95% CI, 1.0010–1.0045; H3, OR 1.0104, 95% CI, 1.0032–1.0176] and mortality [ELA2, HR 1.0014, 95% CI, 1.0004–1.0024; H3, HR 1.0056, 95% CI, 1.0008–1.0115]. The area under the curve value for ELA2 in predicting DIC occurrence was 0.902 (95% CI, 0.816–0.957), and that of H3 was 0.870 (95% CI, 0.778–0.934). Furthermore, biomarkers of NET formation, endothelial cells, and autophagy exhibited a significant correlation [ELA2 and Syn (r = 0.5985, p < 0.0001), LC3B (r = −0.4224, p < 0.0001); H3 and Syn (r = 0.6383, p < 0.0001), LC3B (r = −0.3005, p = 0.0061)].ConclusionIncreased NET formation is significantly associated with sepsis-induced DIC incidence and mortality in sepsis patients, revealing a significant relationship with the autophagy pathway.Clinical Trial Registrationchictr.org.cn, identifier ChiCTR-ROC-17010750.

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