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Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers

Smoking undoubtedly affects human health. Investigating 2318 representative patients at a level 1 trauma center identified delayed wound healing, tissue infections, and/or sepsis as main complications in smokers following trauma and orthopedic surgery. Therefore, smoking cessation is strongly advise...

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Autores principales: Aspera-Werz, Romina H., Mück, Jonas, Linnemann, Caren, Herbst, Moritz, Ihle, Christoph, Histing, Tina, Nussler, Andreas K., Ehnert, Sabrina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774423/
https://www.ncbi.nlm.nih.gov/pubmed/36552632
http://dx.doi.org/10.3390/antiox11122424
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author Aspera-Werz, Romina H.
Mück, Jonas
Linnemann, Caren
Herbst, Moritz
Ihle, Christoph
Histing, Tina
Nussler, Andreas K.
Ehnert, Sabrina
author_facet Aspera-Werz, Romina H.
Mück, Jonas
Linnemann, Caren
Herbst, Moritz
Ihle, Christoph
Histing, Tina
Nussler, Andreas K.
Ehnert, Sabrina
author_sort Aspera-Werz, Romina H.
collection PubMed
description Smoking undoubtedly affects human health. Investigating 2318 representative patients at a level 1 trauma center identified delayed wound healing, tissue infections, and/or sepsis as main complications in smokers following trauma and orthopedic surgery. Therefore, smoking cessation is strongly advised to improve the clinical outcome in these patients, although smoking cessation often fails despite nicotine replacement therapy raising the need for specific interventions that may reduce the complication rate. However, the underlying mechanisms are still unknown. In diabetics, delayed wound healing and infections/sepsis are associated with increased neutrophilic PADI4 expression and formation of neutrophil extracellular traps (NETs). The aim was to investigate if similar mechanisms hold for smokers. Indeed, our results show higher PADI4 expression in active and heavy smokers than non-smokers, which is associated with an increased complication rate. However, in vitro stimulation of neutrophils with cigarette smoke extract (CSE) only moderately induced NET formation despite accumulation of reactive oxygen species (ROS). Physiological levels of nicotine and its main metabolite cotinine more effectively induced NET formation, although they did not actively induce the formation of ROS, but interfered with the activity of enzymes involved in anti-oxidative defense and NET formation. In summary, we propose increased formation of NETs as possible triggers for delayed wound healing, tissue infections, and/or sepsis in smokers after a major trauma and orthopedic surgery. Smoking cessation might reduce this effect. However, our data show that smoking cessation supported by nicotine replacement therapy should be carefully considered as nicotine and its metabolite cotinine effectively induced NET formation in vitro, even without active formation of ROS.
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spelling pubmed-97744232022-12-23 Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers Aspera-Werz, Romina H. Mück, Jonas Linnemann, Caren Herbst, Moritz Ihle, Christoph Histing, Tina Nussler, Andreas K. Ehnert, Sabrina Antioxidants (Basel) Article Smoking undoubtedly affects human health. Investigating 2318 representative patients at a level 1 trauma center identified delayed wound healing, tissue infections, and/or sepsis as main complications in smokers following trauma and orthopedic surgery. Therefore, smoking cessation is strongly advised to improve the clinical outcome in these patients, although smoking cessation often fails despite nicotine replacement therapy raising the need for specific interventions that may reduce the complication rate. However, the underlying mechanisms are still unknown. In diabetics, delayed wound healing and infections/sepsis are associated with increased neutrophilic PADI4 expression and formation of neutrophil extracellular traps (NETs). The aim was to investigate if similar mechanisms hold for smokers. Indeed, our results show higher PADI4 expression in active and heavy smokers than non-smokers, which is associated with an increased complication rate. However, in vitro stimulation of neutrophils with cigarette smoke extract (CSE) only moderately induced NET formation despite accumulation of reactive oxygen species (ROS). Physiological levels of nicotine and its main metabolite cotinine more effectively induced NET formation, although they did not actively induce the formation of ROS, but interfered with the activity of enzymes involved in anti-oxidative defense and NET formation. In summary, we propose increased formation of NETs as possible triggers for delayed wound healing, tissue infections, and/or sepsis in smokers after a major trauma and orthopedic surgery. Smoking cessation might reduce this effect. However, our data show that smoking cessation supported by nicotine replacement therapy should be carefully considered as nicotine and its metabolite cotinine effectively induced NET formation in vitro, even without active formation of ROS. MDPI 2022-12-08 /pmc/articles/PMC9774423/ /pubmed/36552632 http://dx.doi.org/10.3390/antiox11122424 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aspera-Werz, Romina H.
Mück, Jonas
Linnemann, Caren
Herbst, Moritz
Ihle, Christoph
Histing, Tina
Nussler, Andreas K.
Ehnert, Sabrina
Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers
title Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers
title_full Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers
title_fullStr Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers
title_full_unstemmed Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers
title_short Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers
title_sort nicotine and cotinine induce neutrophil extracellular trap formation—potential risk for impaired wound healing in smokers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774423/
https://www.ncbi.nlm.nih.gov/pubmed/36552632
http://dx.doi.org/10.3390/antiox11122424
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