Neutrophil extracellular trap formation and nuclease activity in septic patients.

Autor: Cox LE; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Essen, Germany. linda.cox@uk-essen.de., Walstein K; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Essen, Germany., Völlger L; Institut für Physiologische Chemie, Stiftung Tierärztliche Hochschule Hannover, Bünteweg 2, D-30559, Hannover, Germany., Reuner F; Institut für Physiologische Chemie, Stiftung Tierärztliche Hochschule Hannover, Bünteweg 2, D-30559, Hannover, Germany., Bick A; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Essen, Germany., Dötsch A; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Essen, Germany., Engler A; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Essen, Germany., Peters J; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Essen, Germany., von Köckritz-Blickwede M; Institut für Physiologische Chemie, Stiftung Tierärztliche Hochschule Hannover, Bünteweg 2, D-30559, Hannover, Germany.; Research Center for Emerging Infections and Zoonoses, Stiftung Tierärztliche Hochschule Hannover, Hannover, Germany., Schäfer ST; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen & Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Essen, Germany.; Klinik für Anaesthesiologie, Ludwig-Maximilians-Universität München, Munich, Germany.
Jazyk: angličtina
Zdroj: BMC anesthesiology [BMC Anesthesiol] 2020 Jan 13; Vol. 20 (1), pp. 15. Date of Electronic Publication: 2020 Jan 13.
DOI: 10.1186/s12871-019-0911-7
Abstrakt: Background: There is little knowledge, whether in patients with sepsis neutrophil extracellular trap (NET) formation and NET degrading nuclease activity are altered. Thus, we tested the hypotheses that 1) NET formation from neutrophils of septic patients is increased compared to healthy volunteers, both without stimulation and following incubation with mitochondrial DNA (mtDNA), a damage-associated molecular pattern, or phorbol 12-myristate 13-acetate (PMA; positive control) and 2) that serum nuclease activities are increased as well.
Methods: Following ethic committee approval, we included 18 septic patients and 27 volunteers in this prospective observational trial. Blood was withdrawn and NET formation from neutrophils was analyzed in vitro without stimulation and following incubation with mtDNA (10 μg/well) or PMA (25 nmol). Furthermore, serum nuclease activity was assessed using gel electrophoresis.
Results: In contrast to our hypothesis, in septic patients, unstimulated NET release from neutrophils was decreased by 46.3% (4.3% ± 1.8 SD vs. 8.2% ± 2.9, p ≤ 0.0001) and 48.1% (4.9% ± 2.5 vs. 9.4% ± 5.2, p = 0.002) after 2 and 4 h compared to volunteers. mtDNA further decreased NET formation in neutrophils from septic patients (4.7% ± 1.2 to 2.8% ± 0,8; p = 0.03), but did not alter NET formation in neutrophils from volunteers. Of note, using PMA, as positive control, we ensured that neutrophils were still able to form NETs, with NET formation increasing to 73.2% (±29.6) in septic patients and 91.7% (±7.1) in volunteers (p = 0.22). Additionally, we show that serum nuclease activity (range: 0-6) was decreased in septic patients by 39.6% (3 ± 2 vs 5 ± 0, median and ICR, p = 0.0001) compared to volunteers.
Conclusions: Unstimulated NET formation and nuclease activity are decreased in septic patients. mtDNA can further reduce NET formation in sepsis. Thus, neutrophils from septic patients show decreased NET formation in vitro despite diminished nuclease activity in vivo.
Trial Registration: DRKS00007694, german clinical trials database (DRKS). Retrospectively registered 06.02.2015.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje