中性粒细胞胞外诱捕网在呼吸系统炎性疾病中的作用
Role of Neutrophil Extracellular Trap Net in Respiratory Inflammatory Diseases
摘要: 中性粒细胞被称为先天免疫系统的第一反应细胞，参与感染或者损伤期间的初始早期宿主防御反应。中性粒细胞能够释放“中性粒细胞胞外陷阱”(neutrophil extracellular traps, NETs)参与防御反应，NETs是一种由脱氧核糖核酸(deoxyriboNucleic Acid, DNA)修饰的组蛋白和细胞毒性肽/蛋白质组成的胞外无膜纤维网状结构，其形成途径可分为氮氧化物(nitrogen Oxide, NOX)依赖性NETs形成及氮氧化物非依赖性NETs形成两大类。NETs是把“双刃剑”，除具有抗菌作用外，但过量聚集也会给细胞或组织造成损伤并影响呼吸系统疾病的最终转归。NETs参与慢性阻塞性肺疾病、哮喘、肺囊性纤维化、急性肺损伤等多种以气道炎症为主要特征的呼吸系统疾病过程。抑制NETs表达有助于缓解呼吸系统炎性疾病，为临床防治提供新的靶点和方法。
Abstract: Neutrophils are called the first reaction cells of innate immune system, and participate in the initial early host defense response during infection or injury. Neutrophils can release “neutrophil extra-cellular traps” (NETs) to participate in defense reaction. NETs are an extracellular membraneless fibrous network composed of deoxyriboNucleic Acid (DNA)-modified histone and cytotoxic pep-tide/protein. Its formation pathways can be divided into two categories: nitrogen Oxide (NOX)-dependent NETs formation and nitrogen oxide-independent NETs formation. NETs are a “double-edged sword”, which has antibacterial effect, but excessive aggregation will also cause damage to cells or tissues and affect the final outcome of respiratory diseases. NETs are involved in many respiratory diseases, such as chronic obstructive pulmonary disease, asthma, pulmonary cystic fibrosis and acute lung injury, which are characterized by airway inflammation. Inhibiting the expression of NETs is helpful in alleviating respiratory inflammatory diseases and provides new targets and methods for clinical prevention and treatment.
文章引用：董右青, 李文, 罗书曼, 朱星. 中性粒细胞胞外诱捕网在呼吸系统炎性疾病中的作用[J]. 临床医学进展, 2023, 13(10): 15835-15842. https://doi.org/10.12677/ACM.2023.13102213

参考文献

[1] Kraus, R.F. and Gruber, M.A. (2021) Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System. Frontiers in Immunology, 12, Article ID: 767175. [Google Scholar] [CrossRef] [PubMed]
[2] 冶怡, 乌仁塔娜, 吴金春, 等. 中性粒细胞在肺动脉高压发病中作用的研究进展[J]. 中国病理生理杂志, 2022, 38(10): 1907-1912.
[3] Keir, H.R. and Chalmers, J.D. (2022) Neutrophil Extracellular Traps in Chronic Lung Disease: Impli-cations for Pathogenesis and Therapy. European Respiratory Review, 31, Article ID: 210241. [Google Scholar] [CrossRef] [PubMed]
[4] Takei, H., Araki, A., Watanabe, H., et al. (1996) Rapid Killing of Human Neutrophils by the Potent Activator Phorbol 12-Myristate 13-Acetate (PMA) Accompanied by Changes Dif-ferent from Typical Apoptosis or Necrosis. Journal of Leukocyte Biology, 59, 229-240. [Google Scholar] [CrossRef] [PubMed]
[5] Brinkmann, V., Reichard, U., Goosmann, C., et al. (2004) Neutrophil Ex-tracellular Traps Kill Bacteria. Science, 303, 1532-1535. [Google Scholar] [CrossRef] [PubMed]
[6] 王逸凡, 代蓉, 晏雪梅, 等. 中性粒细胞胞外诱捕网在呼吸道中的作用研究进展[J]. 医学综述, 2021, 27(7): 1272-1277+1283.
[7] 陈熙, 肖锏, 李园园, 等. 中性粒细胞胞外诱捕网与肺部炎症性疾病的关系[J]. 生物化学与生物物理进展, 2019, 46(5): 465-473.
[8] Hamam, H.J. and Palaniyar, N. (2019) Post-Translational Modifications in NETosis and NETs-Mediated Diseases. Biomolecules, 9, Article No. 369. [Google Scholar] [CrossRef] [PubMed]
[9] 毕金凤, 杨爽. 中性粒细胞胞外诱捕网致动脉粥样硬化的分子机制进展[J]. 心血管康复医学杂志, 2023, 32(2): 160-163.
[10] 张克恭, 何文昌, 郭小凤, 等. 中性粒细胞胞外诱捕网形成机制的研究进展[J]. 细胞与分子免疫学杂志, 2020, 36(6): 561-564.
[11] 张凯, 陈虹宇, 李娇, 等. 中性粒细胞细胞外诱捕网的研究进展[J]. 中国畜牧兽医, 2018, 45(1): 206-211.
[12] de Buhr, N. and von Köckritz-Blickwede, M. (2016) How Neutrophil Extracellular Traps Become Visible. Journal of Immunology Research, 2016, Article ID: 4604713. [Google Scholar] [CrossRef] [PubMed]
[13] Chen, F., Liu, Y., Shi, Y., et al. (2022) The Emerging Role of Neutrophilic Extracellular Traps in Intestinal Disease. Gut Pathogens, 14, Article No. 27. [Google Scholar] [CrossRef] [PubMed]
[14] 宋子怡, 张升校, 苏勤怡, 等. 中性粒细胞胞外诱捕网在类风湿关节炎发病机制中的研究进展[J]. 医学研究杂志, 2023, 52(7): 15-18.
[15] 王一茜, 张少康, 赵德安. 中性粒细胞胞外陷阱在风湿免疫性疾病中的作用研究进展[J]. 新乡医学院学报, 2023, 40(7): 696-700.
[16] Ravindran, M., Khan, M.A. and Palaniyar, N. (2019) Neutrophil Extracellular Trap Formation: Physiology, Pathology, and Pharma-cology. Biomolecules, 9, Article No. 365. [Google Scholar] [CrossRef] [PubMed]
[17] Khan, M.A., Farahvash, A., Douda, D.N., et al. (2017) JNK Activation Turns on LPS- and Gram-Negative Bacteria-Induced NADPH Oxi-dase-Dependent Suicidal NETosis. Scientific Reports, 7, Article No. 3409. [Google Scholar] [CrossRef] [PubMed]
[18] 杜高辉, 张青, 魏宇淼. 中性粒细胞胞外诱捕网在动脉粥样硬化中的研究进展[J]. 华中科技大学学报(医学版), 2023, 52(2): 252-256.
[19] Tabrizi, Z.A., Khosrojerdi, A., Aslani, S., et al. (2021) Multi-Facets of Neutrophil Extracellular Trap in Infectious Diseases: Moving beyond Immunity. Microbial Pathogenesis, 158, Article ID: 105066. [Google Scholar] [CrossRef] [PubMed]
[20] Trivedi, A., Khan, M.A., Bade, G., et al. (2021) Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Dis-ease (COPD) Development. Biomedicines, 9, Article No. 53. [Google Scholar] [CrossRef] [PubMed]
[21] 李锋, 周新. 慢性阻塞性肺疾病的发病机制研究进展[J]. 中国呼吸与危重监护杂志, 2019, 18(1): 88-92.
[22] Grabcanovic-Musija, F., Obermayer, A., Stoiber, W., et al. (2015) Neutrophil Extracellular Trap (NET) Formation Characterises Stable and Exacerbated COPD and Correlates with Airflow Limitation. Respiratory Research, 16, Article No. 59. [Google Scholar] [CrossRef] [PubMed]
[23] 范傲, 黄钟, 段宇清, 等. 慢性阻塞性肺疾病患者血浆中性粒细胞胞外诱捕网和白细胞介素-8及白细胞介素-33的表达水平及其临床意义[J]. 中国呼吸与危重监护杂志, 2022, 21(2): 84-89.
[24] Dicker, A.J., Crichton, M.L., Pumphrey, E.G., et al. (2018) Neutrophil Ex-tracellular Traps Are Associated with Disease Severity and Microbiota Diversity in Patients with Chronic Obstructive Pulmonary Disease. Journal of Allergy and Clinical Immunology, 141, 117-127. [Google Scholar] [CrossRef] [PubMed]
[25] Nicchi, S., Giusti, F., Carello, S., et al. (2022) Moraxella Catarrhalis Evades Neutrophil Oxidative Stress Responses Providing a Safer Niche for Nontypeable Haemophilus Influenzae. iScience, 25, Article ID: 103931. [Google Scholar] [CrossRef] [PubMed]
[26] Zou, Y., Chen, X., He, B., et al. (2020) Neutrophil Extracellular Traps Induced by Cigarette Smoke Contribute to Airway Inflammation in Mice. Experimental Cell Research, 389, Article ID: 111888. [Google Scholar] [CrossRef] [PubMed]
[27] Jia, R. and Zhao, X.F. (2020) MicroRNA-497 Functions as an Inflammatory Suppressor via Targeting DDX3Y and Modulating Toll-Like Receptor 4/NF-κB in Cigarette Smoke Ex-tract-Stimulated Human Bronchial Epithelial Cells. The Journal of Gene Medicine, 22, e3137. [Google Scholar] [CrossRef] [PubMed]
[28] Liu, T., Wang, F.P., Wang, G., et al. (2017) Role of Neutrophil Extracellular Traps in Asthma and Chronic Obstructive Pulmonary Disease. Chinese Medical Journal (England), 130, 730-736. [Google Scholar] [CrossRef] [PubMed]
[29] Simpson, J.L., Gibson, P.G., Yang, I.A., et al. (2013) Impaired Macrophage Phagocytosis in Non-Eosinophilic Asthma. Clinical & Experimental Allergy, 43, 29-35. [Google Scholar] [CrossRef] [PubMed]
[30] Zhang, H., Liu, J., Zhou, Y., et al. (2022) Neutrophil Ex-tracellular Traps Mediate m6A Modification and Regulates Sepsis-Associated Acute Lung Injury by Activating Ferropto-sis in Alveolar Epithelial Cells. International Journal of Biological Sciences, 18, 3337-3357. [Google Scholar] [CrossRef] [PubMed]
[31] Han, X.A., Jie, H.Y., Wang, J.H., et al. (2020) Necrostatin-1 Ameliorates Neutrophilic Inflammation in Asthma by Suppressing MLKL Phosphorylation to Inhibiting NETs Release. Frontiers in Immunology, 11, Article No. 666. [Google Scholar] [CrossRef] [PubMed]
[32] Lachowicz-Scroggins, M.E., Dunican, E.M., Charbit, A.R., et al. (2019) Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma. American Journal of Respiratory and Critical Care Medicine, 199, 1076-1085. [Google Scholar] [CrossRef] 
[33] Radermecker, C., Sabatel, C., Vanwinge, C., et al. (2019) Lo-cally Instructed CXCR4hi Neutrophils Trigger Environment-Driven Allergic Asthma through the Release of Neutrophil Extracellular Traps. Nature Immunology, 20, 1444-1455. [Google Scholar] [CrossRef] [PubMed]
[34] Varricchi, G., Modestino, L., Poto, R., et al. (2022) Neutrophil Extracellular Traps and Neutrophil-Derived Mediators as Possible Biomarkers in Bronchial Asthma. Clinical and Ex-perimental Medicine, 22, 285-300. [Google Scholar] [CrossRef] [PubMed]
[35] Meoli, A., Eickmeier, O., Pisi, G., et al. (2022) Impact of CFTR Modulators on the Impaired Function of Phagocytes in Cystic Fibrosis Lung Disease. International Journal of Molecular Sciences, 23, Article No. 12421. [Google Scholar] [CrossRef] [PubMed]
[36] Khan, M.A., Ali, Z.S., Sweezey, N., et al. (2019) Progression of Cystic Fibrosis Lung Disease from Childhood to Adulthood: Neutrophils, Neutrophil Extracellular Trap (NET) For-mation, and NET Degradation. Genes (Basel), 10, Article No. 183. [Google Scholar] [CrossRef] [PubMed]
[37] Ng, H.P., Jennings, S., Wellems, D., et al. (2020) Myeloid CFTR Loss-of-Function Causes Persistent Neutrophilic Inflam-mation in Cystic Fibrosis. Journal of Leukocyte Biology, 108, 1777-1785. [Google Scholar] [CrossRef] 
[38] Law, S.M. and Gray, R.D. (2017) Neutrophil Extracellular Traps and the Dysfunctional Innate Immune Response of Cystic Fibrosis Lung Disease: A Review. Journal of Inflammation (London), 14, Article No. 29. [Google Scholar] [CrossRef] [PubMed]
[39] Tucker, S.L., Sarr, D. and Rada, B. (2021) Neutrophil Extracellu-lar Traps Are Present in the Airways of ENaC-Over- expressing Mice with Cystic Fibrosis-Like Lung Disease. BMC Immunology, 22, Article No. 7. [Google Scholar] [CrossRef] [PubMed]
[40] Marcos, V., Zhou-Suckow, Z., Önder Yildirim, A., et al. (2015) Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction. Mediators of Inflammation, 2015, Ar-ticle ID: 408935. [Google Scholar] [CrossRef] [PubMed]
[41] Scozzi, D., Liao, F., Krupnick, A.S., et al. (2022) The Role of Neutrophil Extracellular Traps in Acute Lung Injury. Frontiers in Immunology, 13, Article ID: 953195. [Google Scholar] [CrossRef] [PubMed]
[42] Yang, S.C., Tsai, Y.F., Pan, Y.L., et al. (2021) Understanding the Role of Neutrophils in Acute Respiratory Distress Syndrome. Biomedical Journal, 44, 439-446. [Google Scholar] [CrossRef] [PubMed]
[43] Lefrançais, E., Mallavia, B., Zhuo, H., et al. (2018) Maladaptive Role of Neutrophil Extracellular Traps in Pathogen-Induced Lung Injury. JCI Insight, 3, e98178. [Google Scholar] [CrossRef] [PubMed]
[44] Caudrillier, A., Kessenbrock, K., Gilliss, B.M., et al. (2012) Platelets Induce Neutrophil Extracellular Traps in Transfusion-Related Acute Lung Injury. Journal of Clinical Investigation, 122, 2661-2671. [Google Scholar] [CrossRef] 
[45] Wang, C., Wei, Z., Han, Z., et al. (2019) Neutrophil Extracellu-lar Traps Promote Cadmium Chloride-Induced Lung Injury in Mice. Environmental Pollution, 254, Article ID: 113021. [Google Scholar] [CrossRef] [PubMed]
[46] Hofbauer, T.M., Mangold, A., Ondracek, A.S., et al. (2021) Deoxyribonuclease 1 Q222R Single Nucleotide Polymorphism and Long-Term Mortality after Acute Myocardial Infarc-tion. Basic Research in Cardiology, 116, Article No. 29. [Google Scholar] [CrossRef] [PubMed]
[47] Liu, S., Su, X., Pan, P., et al. (2016) Neutrophil Extracellular Traps Are Indirectly Triggered by Lipopolysaccharide and Contribute to Acute Lung Injury. Scientific Reports, 6, Article No. 37252. [Google Scholar] [CrossRef] [PubMed]
[48] Li, W.X., Wang, F., Zhu, Y.Q., et al. (2020) Inhibitors of Nitric Oxide Synthase Can Reduce Extracellular Traps from Neutrophils in Asthmatic Children in Vitro. Pediatric Pulmonology, 55, 68-75. [Google Scholar] [CrossRef] [PubMed]
[49] Zhao, J., Wang, H., Zhang, J., et al. (2022) Disulfiram Allevi-ates Acute Lung Injury and Related Intestinal Mucosal Barrier Impairment by Targeting GSDMD-Dependent Pyroptosis. Journal of Inflammation (London), 19, Article No. 17. [Google Scholar] [CrossRef] [PubMed]
[50] Xie, J., Zhu, C.L., Wan, X.J., et al. (2022) GSDMD-Mediated NETosis Promotes the Development of Acute Respiratory Dis-tress Syndrome. European Journal of Immunology, 53, Article ID: 2250011. [Google Scholar] [CrossRef] [PubMed]
[51] Adrover, J.M., Carrau, L., Daßler-Plenker, J., et al. (2022) Disulfiram Inhibits Neutrophil Extracellular Trap Formation and Protects Rodents from Acute Lung Injury and SARS-CoV-2 Infec-tion. JCI Insight, 7, e157342. [Google Scholar] [CrossRef] [PubMed]
[52] 唐启亚, 钟小宁. 中性粒细胞胞外诱捕网在慢性阻塞性肺部疾病免疫发病机制中的研究进展[J]. 医学研究生学报, 2018, 31(8): 869-873.
[53] Totani, L., Amore, C., Piccoli, A., et al. (2021) Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis. Frontiers in Pharmacology, 12, Article ID: 702677. [Google Scholar] [CrossRef] [PubMed]

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