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Animal-Free human whole blood sepsis model to study changes in innate immunity

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peer-reviewed

Erstveröffentlichung
2020-10-14
Authors
Messerer, David Alexander Christian
Vidoni, Laura
Erber, Maike
Stratmann, Alexander Elias Paul
Bauer, Jonas Martin
et al.
Wissenschaftlicher Artikel


Published in
Frontiers in Immunology ; 11 (2020). - Art.-Nr. 571992. - eISSN 1664-3224
Link to original publication
https://dx.doi.org/10.3389/fimmu.2020.571992
Institutions
UKU. Institut für Klinische und Experimentelle Trauma-Immunologie
UKU. Klinik für Anästhesiologie
UKU. Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung
External cooperations
Rudbeck Laboratory Uppsala
Linnaeus University
ISSN
1664-3224
Document version
published version (publisher's PDF)
Abstract
Studying innate immunity in humans is crucial for understanding its role in the pathophysiology of systemic inflammation, particularly in the complex setting of sepsis. Therefore, we standardized a step-by-step process from the venipuncture to the transfer in a human model system, while closely monitoring the inflammatory response for up to three hours. We designed an animal-free, human whole blood sepsis model using a commercially available, simple to use, tubing system. First, we analyzed routine clinical parameters, including cell count and blood gas analysis. Second, we demonstrated that extracellular activation markers (e.g., CD11b and CD62l) as well as intracellular metabolic (intracellular pH) and functional (generation of radical oxygen species) features remained stable after incubation in the whole blood model. Third, we mimicked systemic inflammation during early sepsis by exposure of whole blood to pathogen-associated molecular patterns. Stimulation with lipopolysaccharide revealed the capability of the model system to evoke a sepsis-like inflammatory phenotype of innate immunity. In summary, the presented model serves as a convenient, economic, and reliable platform to study innate immunity in human whole blood, which may yield clinically important insights.
DFG Project THU
SFB 1149 / Gefahrenantwort, Störfaktoren und regeneratives Potential nach akutem Trauma / DFG / 251293561
Publication funding
Open-Access-Förderung durch die Medizinische Fakultät der Universität Ulm
Subject headings
[GND]: Neutrophiler Granulozyt | Entzündung | Sepsis
[MeSH]: Inflammation | Granulocytes | Blood physiological phenomena | Neutrophils | Shock, Septic | Phagocytosis | Receptor, Anaphylatoxin C5a | Lipopolysaccharides | Sepsis
[Free subject headings]: neutrophil granulocytes | blood physiology | ex vivo whole blood model | principles of the 3Rs | neutrophil dysfunction | oxidative burst
[DDC subject group]: DDC 610 / Medicine & health
License
CC BY 4.0 International
https://creativecommons.org/licenses/by/4.0/

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DOI & citation

Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-34046

Messerer, David Alexander Christian et al. (2020): Animal-Free human whole blood sepsis model to study changes in innate immunity. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-34046
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