Dysregulated neutrophil extracellular traps formation in sepsis
Por:
Mulet M., Osuna-Gómez R., Zamora C., Artesero I., Arús M., Vera-Artazcoz P., Cordón A., Vilalta N., San-José P., Abril A., Moliné A., Morán I., López-Contreras J., Vidal S.
Publicada:
28 jun 2023
Ahead of Print:
1 jun 2023
Resumen:
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.
Filiaciones:
Mulet M.:
Inst Recerca Hosp St Creu & St Pau, Dept Inflammatory Dis, Barcelona, Spain
Osuna-Gómez R.:
Inst Recerca Hosp St Creu & St Pau, Dept Inflammatory Dis, Barcelona, Spain
Zamora C.:
Inst Recerca Hosp St Creu & St Pau, Dept Inflammatory Dis, Barcelona, Spain
Artesero I.:
Hosp Santa Creu & Sant Pau, Internal Med Dept, Infect Dis Div, Barcelona, Spain
Arús M.:
Hosp Santa Creu & Sant Pau, Unit Haemostasis & Thrombosis, Barcelona, Spain
Vera-Artazcoz P.:
Hosp Santa Creu & Sant Pau, Intens Care Dept, Barcelona, Spain
Cordón A.:
Hosp Santa Creu & Sant Pau, Intens Care Dept, Barcelona, Spain
Vilalta N.:
Hosp Santa Creu & Sant Pau, Unit Haemostasis & Thrombosis, Barcelona, Spain
San-José P.:
Hosp Santa Creu & Sant Pau, Hematol Dept, Hematol Core Lab, Barcelona, Spain
Abril A.:
Hosp St Joan Deu, Emergency Care Dept, Manresa, Spain
Moliné A.:
Hosp Santa Creu & Sant Pau, Dept Emergency Med, Barcelona, Spain
Morán I.:
Hosp Santa Creu & Sant Pau, Intens Care Dept, Barcelona, Spain
López-Contreras J.:
Hosp Santa Creu & Sant Pau, Internal Med Dept, Infect Dis Div, Barcelona, Spain
Univ Autonoma Barcelona, Dept Med, Cerdanyola Del Valles, Spain
Vidal S.:
Inst Recerca Hosp St Creu & St Pau, Dept Inflammatory Dis, Barcelona, Spain
Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Cerdanyola Del Valles, Spain
Biomed Res Inst St Pau IIB St Pau, Inst Recerca Hosp Santa Creu & St Pau, Dept Inflammatory Dis, Barcelona 08041, Spain
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