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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/12/2424 |
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| author | Romina H. Aspera-Werz Jonas Mück Caren Linnemann Moritz Herbst Christoph Ihle Tina Histing Andreas K. Nussler Sabrina Ehnert |
| author_facet | Romina H. Aspera-Werz Jonas Mück Caren Linnemann Moritz Herbst Christoph Ihle Tina Histing Andreas K. Nussler Sabrina Ehnert |
| author_sort | Romina H. Aspera-Werz |
| collection | DOAJ |
| 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 <i>PADI4</i> expression and formation of neutrophil extracellular traps (NETs). The aim was to investigate if similar mechanisms hold for smokers. Indeed, our results show higher <i>PADI4</i> 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. |
| first_indexed | 2024-03-09T17:23:07Z |
| format | Article |
| id | doaj.art-7bd168105a204d85a1c1d4fed71b9139 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:23:07Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-7bd168105a204d85a1c1d4fed71b91392023-11-24T12:57:51ZengMDPI AGAntioxidants2076-39212022-12-011112242410.3390/antiox11122424Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in SmokersRomina H. Aspera-Werz0Jonas Mück1Caren Linnemann2Moritz Herbst3Christoph Ihle4Tina Histing5Andreas K. Nussler6Sabrina Ehnert7Siegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySiegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySiegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySiegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySiegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySiegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySiegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySiegfried-Weller Institute for Trauma Research, BG Trauma Center, University of Tuebingen, Schnarrenbergstrasse 95, 72070 Tuebingen, GermanySmoking 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 <i>PADI4</i> expression and formation of neutrophil extracellular traps (NETs). The aim was to investigate if similar mechanisms hold for smokers. Indeed, our results show higher <i>PADI4</i> 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.https://www.mdpi.com/2076-3921/11/12/2424smokingnicotinecotinineneutrophil extracellular trapsreactive oxygen species |
| spellingShingle | Romina H. Aspera-Werz Jonas Mück Caren Linnemann Moritz Herbst Christoph Ihle Tina Histing Andreas K. Nussler Sabrina Ehnert Nicotine and Cotinine Induce Neutrophil Extracellular Trap Formation—Potential Risk for Impaired Wound Healing in Smokers Antioxidants smoking nicotine cotinine neutrophil extracellular traps reactive oxygen species |
| 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 | smoking nicotine cotinine neutrophil extracellular traps reactive oxygen species |
| url | https://www.mdpi.com/2076-3921/11/12/2424 |
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