Dysregulated neutrophil extracellular traps formation in sepsis

Abstract

The migration and antimicrobial functions of neutrophils seem to be impaired during sepsis and contribute to the dysregulation of immune responses and disease pathogenesis. However, the role of neutrophil extracellular traps (NETs) remains to be clarified. The study aimed to analyse sequential phenotypic and functional changes of neutrophils during the time following the diagnosis of sepsis. We prospectively enrolled 49 septic and 18 non‐septic patients from the intensive care unit (ICU) and emergency room (ER) and 20 healthy volunteers (HV). Baseline blood samples from septic and non‐septic patients were collected within 12 h of admission to the hospital. Additional septic samples were drawn at 24, 48 and 72 h after baseline. Neutrophil phenotype and degranulation capacity were assessed by flow cytometry and NET formation was quantified by fluorescence. Neutrophils from septic patients exhibited increased CD66b, CD11b and CD177 expression but displayed reduced NET formation at baseline compared with non‐septic patients and HV controls. Neutrophils expressing CD177 interacted less with platelets, were related to reduced NETosis and tended to indicate a worse sepsis outcome. In vitro experiments revealed that neutrophil function is compromised by the origin of sepsis, including the pathogen type and the affected organ. Assessing a decision tree model, our study showed that CD11b expression and NETosis values are useful variables to discriminate septic from non‐septic patients. We conclude that sepsis induces changes in neutrophil phenotype and function that may compromise the effective capacity of the host to eliminate pathogens.

Plasma Dynamics of Neutrophil Extracellular Traps and Cell-Free Dna in Septic and Nonseptic Vasoplegic Shock: A Prospective Comparative Observational Cohort Study

“…The persistent release of NETs and cfDNA over 48 h in sepsis demonstrated in this study is aligned with previous reports using assays based on DNA-associated myeloperoxidase in plasma up to 72 h (29,30), or histone-containing nucleosomes up to 48 h (31). Similarly, increased NETs release measured by DNA-associated myeloperoxidase has been reported following cardiac surgery (14) and increased cfDNA levels were observed following cardiac surgery that persisted up to 5 days postoperatively in cases with a severe inflammatory response (16,17).…”

Integrated multi-omics and artificial intelligence to explore new neutrophils clusters and potential biomarkers in sepsis with experimental validation

“…CD177, a GPI-anchored protein, interacted with the proteinase-3 receptor (PR3) and CD177-PR3 complex regulates neutrophil migration in circulation (33). Previous study showed CD177 was up regulated in neutrophils under sepsis and neutrophil expressed CD177 anchored less with platelets, associated with less NETosis and worse outcome (34). Interestingly, expression of CD177 was negatively with expression of CD10 in neutrophils, which is a marker of immature myeloid cells (35).…”

Integrated Bioinformatics Exploration and Preliminary Clinical Verification for the Identification of Crucial Biomarkers in Severe Cases of COVID-19

“…CD177 was regarded as a prototypical gene for indicating neutrophil activation state because CD177 is a gene exclusive to neutrophils that encoding a membrane glycoprotein. 42 Of note, it was also one of the highest DEGs in severe influenza infection. 43 CD177 protein and mRNA expression increased in circulating neutrophils of patients who had experienced septic shock.…”