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中性粒细胞与烧伤脓毒症

孙炳伟 王逸凡 杨云稀

孙炳伟, 王逸凡, 杨云稀. 中性粒细胞与烧伤脓毒症[J]. 中华烧伤与创面修复杂志, 2024, 40(7): 618-624. DOI: 10.3760/cma.j.cn501225-20240329-00109.
引用本文: 孙炳伟, 王逸凡, 杨云稀. 中性粒细胞与烧伤脓毒症[J]. 中华烧伤与创面修复杂志, 2024, 40(7): 618-624. DOI: 10.3760/cma.j.cn501225-20240329-00109.
Sun BW,Wang YF,Yang YX.Neutrophil and burn sepsis[J].Chin J Burns Wounds,2024,40(7):618-624.DOI: 10.3760/cma.j.cn501225-20240329-00109.
Citation: Sun BW,Wang YF,Yang YX.Neutrophil and burn sepsis[J].Chin J Burns Wounds,2024,40(7):618-624.DOI: 10.3760/cma.j.cn501225-20240329-00109.

中性粒细胞与烧伤脓毒症

doi: 10.3760/cma.j.cn501225-20240329-00109
基金项目: 

国家自然科学基金联合基金重点项目 U21A20370

国家自然科学基金面上项目 82072217, 81772135

详细信息
    通讯作者:

    孙炳伟,Email:sunbinwe@hotmail.com

Neutrophil and burn sepsis

Funds: 

Key Program of Joint Fund of National Natural Science Foundation of China U21A20370

General Program of National Natural Science Foundation of China 82072217, 81772135

More Information
  • 摘要: 脓毒症是严重烧伤最常见的并发症,也是危害危重烧伤患者生命的首要因素。烧伤脓毒症患者的病死率高达75%。中性粒细胞是先天性免疫细胞之一,也是感染部位募集最早、最多的免疫细胞,在局部感染的清除和损伤组织修复方面发挥关键作用。众多研究已深入揭示了烧伤脓毒症的发病和进展机制,中性粒细胞在其中的作用逐渐明朗。该文详细阐述了中性粒细胞在烧伤脓毒症发生、发展中的关键机制,并基于中性粒细胞在烧伤脓毒症中的独特生物学行为,探讨了其在烧伤脓毒症预警与预后判断方面的价值以及烧伤脓毒症的潜在治疗手段。

     

  • 参考文献(53)

    [1] ZhangP,ZouB,LiouYC,et al.The pathogenesis and diagnosis of sepsis post burn injury[J/OL].Burns Trauma,2021,9:tkaa047[2024-03-29].https://pubmed.ncbi.nlm.nih.gov/33654698/.DOI: 10.1093/burnst/tkaa047.
    [2] ArbuthnotMK,GarciaAV.Early resuscitation and management of severe pediatric burns[J].Semin Pediatr Surg,2019,28(1):73-78.DOI: 10.1053/j.sempedsurg.2019.01.013.
    [3] JiJ,FanJ.Neutrophil in reverse migration: role in sepsis[J].Front Immunol,2021,12:656039.DOI: 10.3389/fimmu.2021.656039.
    [4] LeeMJ, BaeJ, LeeJH, et al. Serial change of endotoxin tolerance in a polymicrobial sepsis model[J]. Int J Mol Sci, 2022,23(12):6581. DOI: 10.3390/ijms23126581.
    [5] ZhangYY, NingBT. Signaling pathways and intervention therapies in sepsis [J].Signal Transduct Target Ther, 2021, 6(1): 407.DOI: 10.1038/s41392-021-00816-9.
    [6] 刘馨竹, 李大伟, 蒋敏, 等. 严重烧伤小鼠肠-胰岛轴功能的变化及其作用[J]. 中华烧伤与创面修复杂志, 2024, 40(7): 625-633. DOI: 10.3760/cma.j.cn501225-20240520-00189.
    [7] 邹文, 韩春茂, 金荣华, 等. 不同代谢分期下重症烧伤患者静息能量消耗值的计算公式选择与分析[J]. 中华烧伤与创面修复杂志, 2024, 40(7): 634-642. DOI: 10.3760/cma.j.cn501225-20240229-00080.
    [8] BurnGL, FotiA, MarsmanG, et al. The neutrophil[J]. Immunity, 2021, 54(7): 1377-1391. DOI: 10.1016/j.immuni.2021.06.006.
    [9] ChenY,GuoDZ,ZhuCL,et al.The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways[J].Front Immunol,2023,14:1323797.DOI: 10.3389/fimmu.2023.1323797.
    [10] PatelJM,SapeyE,ParekhD,et al.Sepsis induces a dysregulated neutrophil phenotype that is associated with increased mortality[J].Mediators Inflamm,2018,2018:4065362.DOI: 10.1155/2018/4065362.
    [11] VenetF,MonneretG.Advances in the understanding and treatment of sepsis-induced immunosuppression[J].Nat Rev Nephrol,2018,14(2):121-137.DOI: 10.1038/nrneph.2017.165.
    [12] DemaretJ,VenetF,FriggeriA,et al.Marked alterations of neutrophil functions during sepsis-induced immunosuppression[J].J Leukoc Biol,2015,98(6):1081-1090.DOI: 10.1189/jlb.4A0415-168RR.
    [13] ZhangH,WangY,QuM,et al.Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis[J].Clin Transl Med,2023,13(1):e1170.DOI: 10.1002/ctm2.1170.
    [14] ZhuCL,WangY,LiuQ,et al.Dysregulation of neutrophil death in sepsis[J].Front Immunol,2022,13:963955.DOI: 10.3389/fimmu.2022.963955.
    [15] WangX,QinW,XuX,et al.Endotoxin-induced autocrine ATP signaling inhibits neutrophil chemotaxis through enhancing myosin light chain phosphorylation[J].Proc Natl Acad Sci U S A,2017,114(17):4483-4488.DOI: 10.1073/pnas.1616752114.
    [16] 戚欣欣,杨云稀,孙炳伟.严重烧伤患者早期外周血中性粒细胞趋化功能变化及影响因素[J].中华烧伤杂志,2020,36(3):204-209.DOI: 10.3760/cma.j.cn501120-20190801-00329.
    [17] ShenXF,CaoK,JiangJP,et al.Neutrophil dysregulation during sepsis: an overview and update[J].J Cell Mol Med,2017,21(9):1687-1697.DOI: 10.1111/jcmm.13112.
    [18] SoutoFO,Alves-FilhoJC,TuratoWM,et al.Essential role of CCR2 in neutrophil tissue infiltration and multiple organ dysfunction in sepsis[J].Am J Respir Crit Care Med,2011,183(2):234-242.DOI: 10.1164/rccm.201003-0416OC.
    [19] TangG,YangH,ChenJ,et al.Metformin ameliorates sepsis-induced brain injury by inhibiting apoptosis, oxidative stress and neuroinflammation via the PI3K/Akt signaling pathway[J].Oncotarget,2017,8(58):97977-97989.DOI: 10.18632/oncotarget.20105.
    [20] LiuL,ShaoY,ZhangY,et al.Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)[J/OL].Burns Trauma,2021,9:tkab030[2024-03-29].https://pubmed.ncbi.nlm.nih.gov/34646891/.DOI: 10.1093/burnst/tkab030.
    [21] LiuFC,ChuangYH,TsaiYF,et al.Role of neutrophil extracellular traps following injury[J].Shock,2014,41(6):491-498.DOI: 10.1097/SHK.0000000000000146.
    [22] ShaoY,LiL,LiuL,et al.CD44/ERM/F-actin complex mediates targeted nuclear degranulation and excessive neutrophil extracellular trap formation during sepsis[J].J Cell Mol Med,2022,26(7):2089-2103.DOI: 10.1111/jcmm.17231.
    [23] DenningNL,AzizM,GurienSD,et al.DAMPs and NETs in sepsis[J].Front Immunol,2019,10:2536.DOI: 10.3389/fimmu.2019.02536.
    [24] YeZ,ZouH,LiuS,et al.Diagnostic performance of neutrophil CD64 index in patients with sepsis in the intensive care unit[J].J Int Med Res,2019,47(9):4304-4311.DOI: 10.1177/0300060519860677.
    [25] YinWP,LiJB,ZhengXF,et al.Effect of neutrophil CD64 for diagnosing sepsis in emergency department[J].World J Emerg Med,2020,11(2):79-86.DOI: 10.5847/wjem.j.1920-8642.2020.02.003.
    [26] DemaretJ,VenetF,PlassaisJ,et al.Identification of CD177 as the most dysregulated parameter in a microarray study of purified neutrophils from septic shock patients[J].Immunol Lett,2016,178:122-130.DOI: 10.1016/j.imlet.2016.08.011.
    [27] GongF,LiR,ZhengX,et al.OLFM4 regulates lung epithelial cell function in sepsis-associated ARDS/ALI via LDHA-mediated NF-κB signaling[J].J Inflamm Res,2021,14:7035-7051.DOI: 10.2147/JIR.S335915.
    [28] KangelarisKN,ClemensR,FangX,et al.A neutrophil subset defined by intracellular olfactomedin 4 is associated with mortality in sepsis[J].Am J Physiol Lung Cell Mol Physiol,2021,320(5):L892-L902.DOI: 10.1152/ajplung.00090.2020.
    [29] QiX,YuY,SunR,et al.Identification and characterization of neutrophil heterogeneity in sepsis[J].Crit Care,2021,25(1):50.DOI: 10.1186/s13054-021-03481-0.
    [30] ZhangT,Yu-JingL,MaT.Role of regulation of PD-1 and PD-L1 expression in sepsis[J].Front Immunol,2023,14:1029438.DOI: 10.3389/fimmu.2023.1029438.
    [31] WuYL,YoCH,HsuWT,et al.Accuracy of heparin-binding protein in diagnosing sepsis: a systematic review and meta-analysis[J].Crit Care Med,2021,49(1):e80-e90.DOI: 10.1097/CCM.0000000000004738.
    [32] ZhangW,FangX,GaoC,et al.MDSCs in sepsis-induced immunosuppression and its potential therapeutic targets[J].Cytokine Growth Factor Rev,2023,69:90-103.DOI: 10.1016/j.cytogfr.2022.07.007.
    [33] HuangJ,ChenY,GuoZ,et al.Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis[J/OL].Burns Trauma,2023,11:tkac050[2024-03-29].https://pubmed.ncbi.nlm.nih.gov/36659877/.DOI: 10.1093/burnst/tkac050.
    [34] WangS,SongR,WangZ,et al.S100A8/A9 in inflammation[J].Front Immunol,2018,9:1298.DOI: 10.3389/fimmu.2018.01298.
    [35] DuboisC,MarcéD,FaivreV,et al.High plasma level of S100A8/S100A9 and S100A12 at admission indicates a higher risk of death in septic shock patients[J].Sci Rep,2019,9(1):15660.DOI: 10.1038/s41598-019-52184-8.
    [36] QinQ,LiangL,XiaY.Diagnostic and prognostic predictive values of circulating sTREM-1 in sepsis: a meta-analysis[J].Infect Genet Evol,2021,96:105074.DOI: 10.1016/j.meegid.2021.105074.
    [37] SiskindS,BrennerM,WangP.TREM-1 modulation strategies for sepsis[J].Front Immunol,2022,13:907387.DOI: 10.3389/fimmu.2022.907387.
    [38] JanicovaA,ReljaB.Neutrophil phenotypes and functions in trauma and trauma-related sepsis[J].Shock,2021,56(1):16-29.DOI: 10.1097/SHK.0000000000001695.
    [39] Wiggins-DohlvikK,OakleyRP,HanMS,et al.Tissue inhibitor of metalloproteinase-2 inhibits burn-induced derangements and hyperpermeability in microvascular endothelial cells[J].Am J Surg,2016,211(1):197-205.DOI: 10.1016/j.amjsurg.2015.08.016.
    [40] 袁保红,黄萍,邓鑫梦,等.黄芪甲苷在盲肠末端结扎穿孔诱导脓毒症小鼠中的保护作用研究[J].中国药理学通报,2017,33(10):1452-1456.DOI: 10.3969/j.issn.1001-1978.2017.10.024.
    [41] 杨云稀,黄佳敏,刘璐,等.红色诺卡菌细胞壁骨架对人中性粒细胞生物学功能的调节作用[J].中华烧伤与创面修复杂志,2023,39(7):625-632.DOI: 10.3760/cma.j.cn501225-20230223-00056.
    [42] BironBM, ChungCS, O'BrienXM, et al. Cl-amidine prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model[J]. J Innate Immun, 2017,9(1):22-32. DOI: 10.1159/000448808.
    [43] LewisHD,LiddleJ,CooteJE,et al.Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation[J].Nat Chem Biol,2015,11(3):189-191.DOI: 10.1038/nchembio.1735.
    [44] YeD,YaoJ,DuW,et al.Neutrophil extracellular traps mediate acute liver failure in regulation of mir-223/neutrophil elastase signaling in mice[J].Cell Mol Gastroenterol Hepatol,2022,14(3):587-607.DOI: 10.1016/j.jcmgh.2022.05.012.
    [45] FolcoEJ,MawsonTL,VrommanA,et al.Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1α and cathepsin G[J].Arterioscler Thromb Vasc Biol,2018,38(8):1901-1912.DOI: 10.1161/ATVBAHA.118.311150.
    [46] YostCC,SchwertzH,CodyMJ,et al.Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation[J].J Clin Invest,2016,126(10):3783-3798.DOI: 10.1172/JCI83873.
    [47] SchattnerM.Platelet TLR4 at the crossroads of thrombosis and the innate immune response[J].J Leukoc Biol,2019,105(5):873-880.DOI: 10.1002/JLB.MR0618-213R.
    [48] NealMD,JiaH,EyerB,et al.Discovery and validation of a new class of small molecule Toll-like receptor 4 (TLR4) inhibitors[J].PLoS One,2013,8(6):e65779.DOI: 10.1371/journal.pone.0065779.
    [49] KumarS,GuptaE,KaushikS,et al.Neutrophil extracellular traps: formation and involvement in disease progression[J].Iran J Allergy Asthma Immunol,2018,17(3):208-220.
    [50] OkekeEB,LouttitC,FryC,et al.Inhibition of neutrophil elastase prevents neutrophil extracellular trap formation and rescues mice from endotoxic shock[J].Biomaterials,2020,238:119836.DOI: 10.1016/j.biomaterials.2020.119836.
    [51] LiuS,HuangB,CaoJ,et al.ROS fine-tunes the function and fate of immune cells[J].Int Immunopharmacol,2023,119:110069.DOI: 10.1016/j.intimp.2023.110069.
    [52] MorrisG,GevezovaM,SarafianV,et al.Redox regulation of the immune response[J].Cell Mol Immunol,2022,19(10):1079-1101.DOI: 10.1038/s41423-022-00902-0.
    [53] ChenY, HuangJ, GuoZ, et al. Primitive genotypic characteristics in umbilical cord neutrophils identified by single-cell transcriptome profiling and functional prediction[J]. Front Immunol, 2022,13:970909. DOI: 10.3389/fimmu.2022.970909.
  • Table  1.   中性粒细胞相关烧伤脓毒症预警指标的定义和意义

    指标定义意义
    CD64一种跨膜糖蛋白,IgG的Fc段受体之一,仅在静息中性粒细胞中低表达免疫反应的早期阶段CD64即在中性粒细胞膜表面表达,其对脓毒症患者的早期诊断及预后评价具有重要意义[24, 25]
    CD177/CD10中性粒细胞异质性表达的膜表面蛋白脓毒症患者的中性粒细胞CD177表达升高,CD10表达降低,2种蛋白的水平呈负相关[26]
    嗅素蛋白4一种由外泌体分泌的中性粒细胞特异性颗粒蛋白在烧伤脓毒症患者中嗅素蛋白4阳性中性粒细胞的比例升高,其比例升高与不良预后相关[27, 28]
    PD-L1一种在免疫细胞中表达的共抑制分子脓毒症时,中性粒细胞PD-L1高表达并通过直接接触机制诱导淋巴细胞凋亡。PD-L1的水平与脓毒症的发生、发展密切相关[29, 30]
    肝素结合蛋白来源于中性粒细胞的颗粒蛋白,由活化的中性粒细胞脱颗粒后释放脓毒症时,中性粒细胞等大量释放肝素结合蛋白。肝素结合蛋白在早期识别脓毒症方面具有较强的敏感性和特异性[20,31]
    MDSC粒细胞样骨髓来源的抑制性细胞脓毒症状态下,外周循环MDSC水平升高,从而抑制T细胞增殖和活化[32]
    钙卫蛋白由2个亚基S100A8和S100A9组成,约占中性粒细胞胞质蛋白的40%脓毒症时,血清钙卫蛋白浓度明显升高,提示患者预后不良。S100A8在严重烧伤患者的外周血中高表达,提示患者具有更高的死亡风险[33, 34, 35]
    sTREM-1表达于中性粒细胞等细胞表面的跨膜糖蛋白在脓毒症患者中,外周循环的sTREM-1水平升高,且sTREM-1水平升高与脓毒症休克患者的病死率升高有关[36, 37]
    TLR4表达于中性粒细胞等细胞中的一种Ⅰ型跨膜蛋白脓毒症患者体内TLR4的表达急剧增加,且TLR4可通过相关信号转导通路的激活来推动脓毒症的进展[38]
    注:CD为分化抗原,PD-L1为程序性死亡受体配体1,MDSC为髓源性抑制细胞,sTREM-1为可溶性髓样细胞触发受体-1,TLR4为Toll样受体4
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