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

Aspera-Werz, Romina H.; Mück, Jonas; Herbst, Moritz; Ihle, Christoph; Histing, Tina; Nüssler, Andreas K.; Ehnert, Sabrina

doi:10.3390/antiox11122424

Cited by 3 publications

(4 citation statements)

References 40 publications

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“…Meanwhile, we found 17 blood metabolites that were causally associated with 28-day mortality in sepsis. In addition to the previously reported associations between taurochenodeoxycholate 44 , stearamide 45 , cotinine 46 , methionine 47 , CMPF 48 and sepsis mortality, we also discovered that 4-acetamidobutanoate, glycocholate, 1-stearoylglycerophosphocholine, aspartylphenylalanine, gamma-glutamylphenylalanine, gamma-glutamylglutamate and cysteine-glutathione disulfide is causally associated with 28-day mortality in sepsis. These results may provide biomarkers for early diagnosis of sepsis and targets for timely treatment of sepsis.…”

Section: Discussionsupporting

confidence: 66%

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Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality

Jing,

Zuo,

Liu

et al. 2024

Sci Rep

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Metabolic disorder has been found to be an important factor in the pathogenesis and progression of sepsis. However, the causation of such an association between serum metabolites and sepsis has not been established. We conducted a two-sample Mendelian randomization (MR) study. A genome-wide association study of 486 human serum metabolites was used as the exposure, whereas sepsis and sepsis mortality within 28 days were set as the outcomes. In MR analysis, 6 serum metabolites were identified to be associated with an increased risk of sepsis, and 6 serum metabolites were found to be related to a reduced risk of sepsis. Furthermore, there were 9 metabolites positively associated with sepsis-related mortality, and 8 metabolites were negatively correlated with sepsis mortality. In addition, “glycolysis/gluconeogenesis” (p = 0.001), and “pyruvate metabolism” (p = 0.042) two metabolic pathways were associated with the incidence of sepsis. This MR study suggested that serum metabolites played significant roles in the pathogenesis of sepsis, which may provide helpful biomarkers for early disease diagnosis, therapeutic interventions, and prognostic assessments for sepsis.

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Section: Discussionsupporting

confidence: 66%

“…Plasma cotinine is a nicotine metabolite. Romina et al have shown that increased neutrophil extracellular traps (NETs) formation may be a trigger for sepsis in smokers and cotinine could effectively induce the formation of NETs, which may be the main reason why cotinine aggravates the death of patients with sepsis 46 .…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality

Jing,

Zuo,

Liu

et al. 2024

Sci Rep

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“…Therefore, it is difficult to define the formation form of NETs in diabetic wounds or the proportion of NETs formed in various forms. Infection, high glucose environment, and even smoking are thought to affect NETs formation, thereby interfering with wound healing 106‐108 . At present, the research on NETs in various types of wounds is limited, and the mechanism of NETs formation in diabetic wounds mediated by different factors still needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

“…Infection, high glucose environment, and even smoking are thought to affect NETs formation, thereby interfering with wound healing. [106][107][108] At present, the research on NETs in various types of wounds is limited, and the mechanism of NETs formation in diabetic wounds mediated by different factors still needs to be further studied. In addition, the concentration of NETs is also an important factor, and Yang et al found that NETs can inhibit diabetic wound healing by reducing angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils extracellular traps and ferroptosis in diabetic wounds

Huang

Ding

Wang

et al. 2023

International Wound Journal

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Wound healing is an extremely complex process involving multiple levels of cells and tissues. It is mainly completed through four stages: haemostasis, inflammation, proliferation, and remodelling. When any one of these stages is impaired, it may lead to delayed healing or even transformation into chronic refractory wounds. Diabetes is a kind of common metabolic disease that affects approximately 500 million people worldwide, 25% of whom develop skin ulcers that break down repeatedly and are difficult to heal, making it a growing public health problem. Neutrophils extracellular traps and ferroptosis are new types of programmed cell death identified in recent years and have been found to interact with diabetic wounds. In this paper, the normal wound healing and interfering factors of the diabetic refractory wound were outlined. The mechanism of two kinds of programmed cell death was also described, and the interaction mechanism between different types of programmed cell death and diabetic refractory wounds was discussed.

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Molecular and functional changes in neutrophilic granulocytes induced by nicotine: a systematic review and critical evaluation

Brembach,

Sabat,

Witte

et al. 2023

Front. Immunol.

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BackgroundOver 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far.ObjectivesThe aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release.Material and methodsThis review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed® and Web of Science™ in February 2023. Inclusion criteria comprised English written research articles, showing in vitro studies on the direct impact of nicotine on specified human neutrophil functions.ResultsOf the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (>3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of β-glucuronidase and myeloperoxidase.ConclusionNicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.

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

Cited by 3 publications

References 40 publications

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality

Neutrophils extracellular traps and ferroptosis in diabetic wounds

Molecular and functional changes in neutrophilic granulocytes induced by nicotine: a systematic review and critical evaluation

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