Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model

Andre Bredthauer,1,2 Angela Geiger,1 Michael Gruber,1 Sophie-Marie Pfaehler,1 Walter Petermichl,1 Diane Bitzinger,1 Thomas Metterlein,1,3 Timo Seyfried1,4 1Department of Anesthesiology, University Medical Center Regensburg, Regensburg, Germany; 2Department of Neurology at the University of Regensbur...

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Autores principales:	Bredthauer A, Geiger A, Gruber M, Pfaehler SM, Petermichl W, Bitzinger D, Metterlein T, Seyfried T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	polymorphonuclear neutrophils sepsis propofol immune modulation lps Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/623f2f99ffb04cf68908bc20eaa7e7bb
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spelling	oai:doaj.org-article:623f2f99ffb04cf68908bc20eaa7e7bb2021-12-02T18:49:37ZPropofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model1178-7031https://doaj.org/article/623f2f99ffb04cf68908bc20eaa7e7bb2021-08-01T00:00:00Zhttps://www.dovepress.com/propofol-ameliorates-exaggerated-human-neutrophil-activation-in-a-lps--peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Andre Bredthauer,1,2 Angela Geiger,1 Michael Gruber,1 Sophie-Marie Pfaehler,1 Walter Petermichl,1 Diane Bitzinger,1 Thomas Metterlein,1,3 Timo Seyfried1,4 1Department of Anesthesiology, University Medical Center Regensburg, Regensburg, Germany; 2Department of Neurology at the University of Regensburg – Center for Vascular Neurology and Intensive Care Medicine, Regensburg, Germany; 3Department of Anesthesiology, Ansbach Hospital, Ansbach, Germany; 4Department of Anesthesiology, Ernst von Bergmann Hospital, Potsdam, GermanyCorrespondence: Michael GruberDepartment of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg, 93053, GermanyTel +49 941-944-17870Fax +49 941-944-7802Email michael.gruber@ukr.deBackground: Sepsis is a leading cause of morbidity and mortality worldwide. Many patients suffering from sepsis are treated on intensive care units and many of them require mechanical ventilation under sedation or general anesthesia. Propofol, a drug used for these purposes, is known to interact with polymorphonuclear granulocytes (PMNs). Therefore, the aim of this study was to investigate the influence of propofol on PMN functions after experimental Gram-negative induced sepsis using lipopolysaccharide (LPS) stimulation.Methods: A total of 34 granulocyte-enriched samples were collected from healthy subjects. PMNs were isolated by density gradient centrifugation and incubated simultaneously with either 6 μg/mL or 60 μg/mL propofol, or none (control). Additionally, the experimental sepsis samples were incubated with either 40 pg/mL or 400 pg/mL LPS. Live cell imaging was conducted in order to observe granulocyte chemotactic migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression.Results: Propofol led to significantly reduced PMN track length (p < 0.001) and track speed (p < 0.014) after LPS-induced sepsis in a dose-dependent manner. NETosis (p = 0.018) and ROS production (p = 0.039) were accelerated by propofol without LPS incubation, indicating improved immune function. Propofol also ameliorated LPS-induced increased NETosis and ROS-production. Antigen expression for CD11b, CD62l and CD66b was unaffected by propofol.Conclusion: Propofol improves LPS-induced exaggerated PMN activation in an ex vivo model. Beneficial effects due to restored immune function in septic patients might be possible, but needs further investigation.Keywords: polymorphonuclear neutrophils, sepsis, propofol, immune modulation, LPSBredthauer AGeiger AGruber MPfaehler SMPetermichl WBitzinger DMetterlein TSeyfried TDove Medical Pressarticlepolymorphonuclear neutrophilssepsispropofolimmune modulationlpsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 3849-3862 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	polymorphonuclear neutrophils sepsis propofol immune modulation lps Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	polymorphonuclear neutrophils sepsis propofol immune modulation lps Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Bredthauer A Geiger A Gruber M Pfaehler SM Petermichl W Bitzinger D Metterlein T Seyfried T Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model
description	Andre Bredthauer,1,2 Angela Geiger,1 Michael Gruber,1 Sophie-Marie Pfaehler,1 Walter Petermichl,1 Diane Bitzinger,1 Thomas Metterlein,1,3 Timo Seyfried1,4 1Department of Anesthesiology, University Medical Center Regensburg, Regensburg, Germany; 2Department of Neurology at the University of Regensburg – Center for Vascular Neurology and Intensive Care Medicine, Regensburg, Germany; 3Department of Anesthesiology, Ansbach Hospital, Ansbach, Germany; 4Department of Anesthesiology, Ernst von Bergmann Hospital, Potsdam, GermanyCorrespondence: Michael GruberDepartment of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg, 93053, GermanyTel +49 941-944-17870Fax +49 941-944-7802Email michael.gruber@ukr.deBackground: Sepsis is a leading cause of morbidity and mortality worldwide. Many patients suffering from sepsis are treated on intensive care units and many of them require mechanical ventilation under sedation or general anesthesia. Propofol, a drug used for these purposes, is known to interact with polymorphonuclear granulocytes (PMNs). Therefore, the aim of this study was to investigate the influence of propofol on PMN functions after experimental Gram-negative induced sepsis using lipopolysaccharide (LPS) stimulation.Methods: A total of 34 granulocyte-enriched samples were collected from healthy subjects. PMNs were isolated by density gradient centrifugation and incubated simultaneously with either 6 μg/mL or 60 μg/mL propofol, or none (control). Additionally, the experimental sepsis samples were incubated with either 40 pg/mL or 400 pg/mL LPS. Live cell imaging was conducted in order to observe granulocyte chemotactic migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression.Results: Propofol led to significantly reduced PMN track length (p < 0.001) and track speed (p < 0.014) after LPS-induced sepsis in a dose-dependent manner. NETosis (p = 0.018) and ROS production (p = 0.039) were accelerated by propofol without LPS incubation, indicating improved immune function. Propofol also ameliorated LPS-induced increased NETosis and ROS-production. Antigen expression for CD11b, CD62l and CD66b was unaffected by propofol.Conclusion: Propofol improves LPS-induced exaggerated PMN activation in an ex vivo model. Beneficial effects due to restored immune function in septic patients might be possible, but needs further investigation.Keywords: polymorphonuclear neutrophils, sepsis, propofol, immune modulation, LPS
format	article
author	Bredthauer A Geiger A Gruber M Pfaehler SM Petermichl W Bitzinger D Metterlein T Seyfried T
author_facet	Bredthauer A Geiger A Gruber M Pfaehler SM Petermichl W Bitzinger D Metterlein T Seyfried T
author_sort	Bredthauer A
title	Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model
title_short	Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model
title_full	Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model
title_fullStr	Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model
title_full_unstemmed	Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model
title_sort	propofol ameliorates exaggerated human neutrophil activation in a lps sepsis model
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/623f2f99ffb04cf68908bc20eaa7e7bb
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Propofol Ameliorates Exaggerated Human Neutrophil Activation in a LPS Sepsis Model

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