title: Hyperbaric Oxygen Reduces Production of Reactive Oxygen Species in Neutrophils from Polytraumatized Patients Yielding in the Inhibition of p38 MAP Kinase and Downstream Pathways.
abstract: Trauma represents the leading cause of death among young people in western countries. Among the beneficial role of neutrophils in host defence, excessive priming and activation of neutrophils after major trauma lead to an overwhelming inflammatory response and secondary host tissue injury due to the release of toxic metabolites and enzymes. Hyperbaric oxygen (HBO) therapy has been proposed to possess antiinflammatory effects and might represent an appropriate therapeutic option to lower inflammation in a broad range of patients. Here, we studied the effects of HBO on the activity of neutrophils isolated from severely injured patients (days 1-2 after trauma), in fact on the production of reactive oxygen species (ROS) and release of neutrophil extracellular traps (NETs). We found exposure to HBO therapy to significantly diminish phorbol-12-myristate-13-acetate (PMA)-induced ROS production in neutrophils isolated from patients and healthy volunteers. At the same time, marked decrease in NETs release was found in control cells and a less pronounced reduction in patient neutrophils. Impaired ability to produce ROS following exposure to HBO was demonstrated to be linked to a strong downregulation of the activity of p38 MAPK. Only slight suppression of ERK activity could be found. In addition, HBO did not influence neutrophil chemotaxis or apoptosis, respectively. Collectively, this study shows for the first time that HBO therapy suppresses ROS production in inflammatory human neutrophils, and thus might impair ROS-dependent pathways, e.g. kinases activation and NETs release. Thus, HBO might represent a feasible therapy for patients suffering from systemic inflammation, including those with multiple trauma.
authors.affiliation: University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Grimberg-Peters
authors.affiliation: University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Büren
authors.affiliation: University Hospital Düsseldorf, Department of Trauma and Hand Surgery, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Windolf
authors.affiliation: Heart Center of the University of Cologne, Department of Cardiothoracic Surgery, Kerpener Str. 62, 50937, Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wahlers
authors.affiliation: Heart Center of the University of Cologne, Department of Cardiothoracic Surgery, Kerpener Str. 62, 50937, Cologne, Germany.
authors.forename: Adnana
authors.identifier: http://orcid.org/0000-0001-6467-3544
authors.initials: A
authors.lastname: Paunel-Görgülü
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D016638:Critical Illness / Q000628:therapy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D065206:Extracellular Traps / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006931:Hyperbaric Oxygenation; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010703:Phorbol Esters; D017382:Reactive Oxygen Species; C119222:phorbol-12-myristate; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases