PDF(Pubmed)
Abstract：
Over 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.
The 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.
This 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.
Of 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.
Nicotine 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.
The 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.
This 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.
Of 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.
Nicotine 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.
摘要：
■全球有超过11亿人吸烟。生物碱尼古丁是烟草的突出和令人上瘾的成分。除了肿瘤和心血管疾病，烟草消费与多种慢性炎症性疾病有关。尽管嗜中性粒细胞（嗜中性粒细胞）在许多此类疾病的发病机理中起作用，迄今为止,尚未对尼古丁对中性粒细胞的影响进行系统评价.
■这项系统评价的目的是评估尼古丁对人类中性粒细胞功能的直接影响，特别是细胞死亡/损伤，凋亡，趋化性,一般运动性，粘附分子表达，类花生酸合成，细胞因子/趋化因子表达，中性粒细胞胞外陷阱（NET）的形成，吞噬作用,活性氧（ROS）的产生，净抗微生物活性，和酶释放。
■这项审查是根据PRISMA指南进行的。2023年2月在NCBIPubmed®和WebofScience™数据库中进行了文献检索。纳入标准包括英文书面研究文章，显示了尼古丁对特定人类中性粒细胞功能的直接影响的体外研究。
■在最初确定的532篇文章中，经过几个评估步骤，最终汇编了34篇文章的数据。所考虑的研究在方法论方面千差万别。虽然在高浓度（>3mmol/l）尼古丁开始对嗜中性粒细胞具有细胞毒性，通常在长暴露时间（24-72小时）的吸烟者血液中达到的浓度（在nmol/l范围内）支持嗜中性粒细胞的存活。吸烟相关的尼古丁浓度也增加了嗜中性粒细胞对几种化学引诱物的趋化性，提高了弹性蛋白酶的产量，脂质运载蛋白2，CXCL8，白三烯B4和前列腺素E2，并降低其整合素表达。此外，而尼古丁损害中性粒细胞吞噬和抗微生物活性，一系列研究表明网络形成增加。然而,发现了对ROS生成的相互矛盾的影响，β-葡糖醛酸酶和髓过氧化物酶的选择素表达和释放。
■尼古丁似乎支持中性粒细胞在组织中的存在以及炎症和选定的组织损伤活性，并降低其抗微生物功能，提示尼古丁通过影响中性粒细胞生物学对慢性炎症性疾病的发病机理有直接作用。
■这项系统评价的目的是评估尼古丁对人类中性粒细胞功能的直接影响，特别是细胞死亡/损伤，凋亡，趋化性,一般运动性，粘附分子表达，类花生酸合成，细胞因子/趋化因子表达，中性粒细胞胞外陷阱（NET）的形成，吞噬作用,活性氧（ROS）的产生，净抗微生物活性，和酶释放。
■这项审查是根据PRISMA指南进行的。2023年2月在NCBIPubmed®和WebofScience™数据库中进行了文献检索。纳入标准包括英文书面研究文章，显示了尼古丁对特定人类中性粒细胞功能的直接影响的体外研究。
■在最初确定的532篇文章中，经过几个评估步骤，最终汇编了34篇文章的数据。所考虑的研究在方法论方面千差万别。虽然在高浓度（>3mmol/l）尼古丁开始对嗜中性粒细胞具有细胞毒性，通常在长暴露时间（24-72小时）的吸烟者血液中达到的浓度（在nmol/l范围内）支持嗜中性粒细胞的存活。吸烟相关的尼古丁浓度也增加了嗜中性粒细胞对几种化学引诱物的趋化性，提高了弹性蛋白酶的产量，脂质运载蛋白2，CXCL8，白三烯B4和前列腺素E2，并降低其整合素表达。此外，而尼古丁损害中性粒细胞吞噬和抗微生物活性，一系列研究表明网络形成增加。然而,发现了对ROS生成的相互矛盾的影响，β-葡糖醛酸酶和髓过氧化物酶的选择素表达和释放。
■尼古丁似乎支持中性粒细胞在组织中的存在以及炎症和选定的组织损伤活性，并降低其抗微生物功能，提示尼古丁通过影响中性粒细胞生物学对慢性炎症性疾病的发病机理有直接作用。
