血小板-中性粒细胞相互作用在脓毒症免疫血栓形成中的研究进展*

doi:10.3969/j.issn.1671-2587.2026.02.022

临床输血与检验 ›› 2026, Vol. 28 ›› Issue (2): 286-292.DOI: 10.3969/j.issn.1671-2587.2026.02.022

血小板-中性粒细胞相互作用在脓毒症免疫血栓形成中的研究进展^*

叶至顺^1,2, 李冠球^1,3, 伍昌林^1,4

¹广东医科大学第一临床医学院,广东湛江 524023;
²华南理工大学附属第六医院（佛山市南海区人民医院）输血科,广东佛山 528200;
³南方医科大学第八附属医院（佛山市顺德区第一人民医院）输血科,广东佛山 528300;
⁴深圳市第二人民医院（深圳大学第一附属医院）输血科,广东深圳 518035

收稿日期:2025-06-05 接受日期:2025-08-01 出版日期:2026-04-20 发布日期:2026-04-22
通讯作者: 伍昌林,主要从事血液免疫学方面研究,（E-mail）wuchlin@126.com。
作者简介:叶至顺,主要从事输血医学、血液免疫学方面研究,（E-mail）lyyezs@scut.edu.cn。
基金资助:
^*本课题受广东省深圳科技计划项目（No.JCYJ20240813141121029）资助

Research Progress on the Interaction between Platelets and Neutrophils in Immunothrombosis during Sepsis

YE Zhishun^1,2, LI Guanqiu^1,3, WU Changlin^1,4

¹The First Clinical Medical College of Guangdong Medical University, Zhanjiang 524023;
²Transfusion Department, School of Medicine, the Sixth Affiliated Hospital of South China University of Technology (Nanhai District People's Hospital of Foshan), Foshan 528200;
³Transfusion Department, The Eighth Affiliated Hospital of Southern Medical University (Shunde District First People's Hospital of Foshan), Foshan 528300;
⁴Transfusion Department, Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University), Shenzhen 518035;

Received:2025-06-05 Accepted:2025-08-01 Online:2026-04-20 Published:2026-04-22

摘要/Abstract

摘要： 脓毒症是由机体对感染反应失调所致的器官功能障碍,免疫血栓是其核心病理机制之一。近年来,血小板-中性粒细胞相互作用作为连接炎症与凝血失衡中的关键环节日益受到关注。尽管相关研究不断深入,但其形成调控机制,临床评估价值及靶向干预仍缺乏系统总结。本综述围绕血小板-中性粒细胞复合物（platelet-neutrophil complexes, PNCs）与中性粒细胞释放胞外诱捕网（neutrophil extracellular traps, NETs）,梳理其在脓毒症中的指标意义、致病机制、激活调控通路及靶向干预的研究进展,强调其在疾病评估与个体化治疗中的应用前景,并指出当前在机制整合、检测手段与临床转化方面的挑战。旨在为进一步探究脓毒症中的免疫血栓机制与精准治疗策略提供理论支持与研究方向。

关键词: 脓毒症, 血小板, 中性粒细胞, 免疫血栓, 血小板-中性粒细胞复合物, 中性粒细胞胞外诱捕网

Abstract: Sepsis is an organ dysfunction syndrome caused by a dysregulated host response to infection, and immunothrombosis is one of its core pathological mechanisms. In recent years, platelet-neutrophil interactions have attracted increasing attention as a key link bridging inflammation and coagulation imbalance. Although research in this area is steadily advancing, there is still a lack of systematic summaries regarding its regulatory mechanisms, clinical evaluation value, and targeted interventions. This review focuses on platelet-neutrophil complexes (PNCs) and neutrophil extracellular traps (NETs), summarizing current progress in their biomaker significance, roles in pathogenesis, activation of regulatory pathways, and potential targeted interventions in sepsis. It also highlights their application prospects in disease assessment and individualized treatment, while addressing the exisiting challenges in mechanistic integration, detection methodologies, and clinical transformation. The aim is to provide theoretical support and research directions for further elucidating the mechanisms of immunothrombosis in sepsis and developing precision treatment strategies.

Key words: Sepsis, Platelet, Neutrophil, Immunothrombosis, Platelet-neutrophil complex, Neutrophil extracellular traps

中图分类号:

R631.2R392.12R364.1

叶至顺, 李冠球, 伍昌林. 血小板-中性粒细胞相互作用在脓毒症免疫血栓形成中的研究进展^*[J]. 临床输血与检验, 2026, 28(2): 286-292.

YE Zhishun, LI Guanqiu, WU Changlin. Research Progress on the Interaction between Platelets and Neutrophils in Immunothrombosis during Sepsis[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2026, 28(2): 286-292.

参考文献

[1] Singer M,Deutschman C S,Seymour C W,et al.The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA,2016,315(8):801-810.
[2] La Via L,Sangiorgio G,Stefani S,et al.The global burden of sepsis and septic shock[J]. Epidemiologia,2024,5(3):456-478.
[3] Engelmann B,Massberg S.Thrombosis as an intravascular effector of innate immunity[J]. Nat Rev Immunol,2013, 13(1):34-45.
[4] Aklilu A,Lai M S,Jiang Z W,et al.Immunothrombosis in sepsis: cellular crosstalk,molecular triggers,and therapeutic opportunities-a review[J]. Int J Mol Sci, 2025,26(13):6114.
[5] 彭晓欢,李莉娟,张鸿彬,等. 免疫血栓形成——脓毒症中的一把“双刃剑”[J/OL]. 中华危重症医学杂志(电子版),2022,15(3):241-245.
[6] Hua T Z,Yao F H,Wang H T,et al.Megakaryocyte in sepsis: the trinity of coagulation,inflammation and immunity[J]. Crit Care,2024,28(1):442.
[7] Velissaris D,Karamouzos V,Paraskevas T, et al.Neutrophil extracellular traps in the prognosis of sepsis: a current update[J]. Medicina,2025,61(7):1145.
[8] Su Y F,Li D G,Deng S Y,et al.Prognostic value of coagulation and fibrinolysis function indexes and NETs for sepsis patients[J]. Am J Transl Res,2023,15(6):4164-4171.
[9] Yokoyama Y,Ito T,Yasuda T,et al.Circulating histone H3 levels in septic patients are associated with coagulopathy,multiple organ failure,and death: a single-center observational study[J]. Thromb J,2019,17:1.
[10] Qiao X,Kashiouris M G,L'Heureux M,et al. Biological effects of intravenous vitamin C on neutrophil extracellular traps and the endothelial glycocalyx in patients with sepsis-induced ARDS[J]. Nutrients,2022, 14(20):4415.
[11] Chen Y Q,Mao R L,Chang Q,et al.A causal effects of neutrophil extracellular traps and its biomarkers on acute respiratory distress syndrome: a two-sample Mendelian randomization study[J]. Sci Rep,2025,15(1): 11995.
[12] He J,Zheng F,Qiu L H,et al.Plasma neutrophil extracellular traps in patients with sepsis-induced acute kidney injury serve as a new biomarker to predict 28-day survival outcomes of disease[J]. Front Med,2024,11: 1496966.
[13] Cappenberg A,Kardell M,Zarbock A.Selectin-mediated signaling—shedding light on the regulation of integrin activity in neutrophils[J]. Cells, 2022,11(8):1310.
[14] Cox D.Sepsis—it is all about the platelets[J]. Front Immunol,2023,14:1210219.
[15] Zhang H J,Goswami J,Varley P,et al.Hepatic surgical stress promotes systemic immunothrombosis that results in distant organ injury[J]. Front Immunol, 2020,11:987.
[16] 冶怡,格日力,乌仁塔娜. 血小板与中性粒细胞相互作用在血管病变中的研究进展[J]. 中国病理生理杂志,2022, 38(8):1526-1532.
[17] Wang Y Z,Luo L T,Braun O Ö,et al.Neutrophil extracellular trap-microparticle complexes enhance thrombin generation via the intrinsic pathway of coagulation in mice[J]. Sci Rep,2018,8(1):4020.
[18] De Los Reyes-García A M,Aroca A,Arroyo A B,et al. Neutrophil extracellular trap components increase the expression of coagulation factors[J]. Biomed Rep,2019, 10(3):195-201.
[19] Behzadifard M,Soleimani M.NETosis and SARS-COV-2 infection related thrombosis: a narrative review[J]. Thromb J,2022,20(1):13.
[20] Yin J,Chi Y W,Liu D Y,et al.Unfractionated heparin attenuated histone-induced pulmonary endothelial glycocalyx injury through Ang/Tie2 pathway[J]. J Inflamm,2025,22(1):9.
[21] Teo A,Chan L L Y,Cheung C,et al. Myeloperoxidase inhibition may protect against endothelial glycocalyx shedding induced by COVID-19 plasma[J]. Commun Med,2023,3(1):62.
[22] Chen J,Wang T,Li X O,et al.DNA of neutrophil extracellular traps promote NF-κB-dependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease[J]. Signal Transduct Target Ther, 2024,9(1):163.
[23] De Luca G,Goette N P,Lev P R,et al.Elevated levels of damage-associated molecular patterns HMGB1 and S100A8/A9 coupled with toll-like receptor-triggered monocyte activation are associated with inflammation in patients with myelofibrosis[J]. Front Immunol,2024,15: 1365015.
[24] 冯子阳,黄韦华,唐河山,等. 红细胞储存损伤释放的游离血红素通过内质网应激诱导NETosis加重创伤-失血性休克小鼠模型炎症反应的作用机制研究[J]. 临床输血与检验,2025,27(5):585-593.
[25] Burmeister A,Vidal-Y-Sy S,Liu X B,et al. Impact of neutrophil extracellular traps on fluid properties,blood flow and complement activation[J]. Front Immunol, 2022,13:1078891.
[26] Perdomo J,Leung H H L. Immune thrombosis: exploring the significance of immune complexes and NETosis[J]. Biology,2023,12(10):1332.
[27] Pan Y X,Peng M Y,Tong M D,et al.The globular domain of extracellular histones mediates cytotoxicity via membrane disruption mechanism[J]. J Biol Chem,2025, 301(1):108038.
[28] Zhou Y L,Xu Z D,Liu Z Q.Impact of neutrophil extracellular traps on thrombosis formation: new findings and future perspective[J]. Front Cell Infect Microbiol,2022,12:910908.
[29] Fukuta T,Okada H,Takemura G,et al.Neutrophil elastase inhibition ameliorates endotoxin-induced myocardial injury accompanying degradation of cardiac capillary glycocalyx[J]. Shock,2020,54(3):386-393.
[30] Leberzammer J,Von Hundelshausen P.Chemokines, molecular drivers of thromboinflammation and immunothrombosis[J]. Front Immunol,2023,14:1276353.
[31] Etulain J,Martinod K,Wong S L,et al.P-selectin promotes neutrophil extracellular trap formation in mice[J]. Blood,2015,126(2):242-246.
[32] Zucoloto A Z,Jenne C N.Platelet-neutrophil interplay: insights into neutrophil extracellular trap (NET)-driven coagulation in infection[J]. Front Cardiovasc Med,2019, 6:85.
[33] Fonseca Z,Díaz-Godínez C,Mora N,et al.Entamoeba histolytica induce signaling via raf/MEK/ERK for neutrophil extracellular trap (NET) formation[J]. Front Cell Infect Microbiol,2018,8:226.
[34] Neeli I,Moarefian M,Kuseladass J,et al.Neutrophil attachment via Mac-1 (α(M)β(2);CD11b/CD18;CR3) integrins induces PAD4 deimination of profilin and histone H3[J]. Philos Trans R Soc Lond B Biol Sci,2023, 378(1890):20220247.
[35] Pruenster M,Immler R,Roth J,et al.E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation[J]. Nat Immunol,2023, 24(12):2021-2031.
[36] Deng M,Guo H T,Tam J W,et al.Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR[J]. J Exp Med,2019, 216(12):2838-2853.
[37] Burkard P,Schonhart C,Vögtle T,et al.A key role for platelet GPVI in neutrophil recruitment, migration,and NETosis in the early stages of acute lung injury[J]. Blood,2023,142(17):1463-1477.
[38] Yang M N,Jiang H J,Ding C,et al. STING activation in platelets aggravates septic thrombosis by enhancing platelet activation and granule secretion[J]. Immunity, 2023,56(5):1013-1026.e6.
[39] Dash U K,Mazumdar D,Singh S.High mobility group box protein (HMGB1): a potential therapeutic target for diabetic encephalopathy[J]. Mol Neurobiol,2024, 61(10):8188-8205.
[40] 乔剑,刁春红,于洋,等. 吴茱萸碱通过调节HMGB1/TLR4/NF-κB信号通路减轻大鼠输血相关性急性肺损伤[J]. 临床输血与检验,2023,25(5):599-606.
[41] Gao X,Zhao X Y,Li J C,et al.Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke[J]. Cell Commun Signal,2024,22(1):50.
[42] Jiang H M,Chen S,Gui X,et al.Platelet NLRP6 protects against microvascular thrombosis in sepsis[J]. Blood,2025,146(3):382-395.
[43] Tsourouktsoglou T D,Warnatsch A,Ioannou M,et al.Histones,DNA,and citrullination promote neutrophil extracellular trap inflammation by regulating the localization and activation of TLR4[J]. Cell Rep,2020, 31(5):107602.
[44] Ma F,Chang X J,Wang G Y,et al.Streptococcus suis serotype 2 stimulates neutrophil extracellular traps formation via activation of p38 MAPK and ERK1/2[J]. Front Immunol,2018,9:2854.
[45] Chen W A,Boskovic D S.Neutrophil extracellular DNA traps in response to infection or inflammation,and the roles of platelet interactions[J]. Int J Mol Sci,2024, 25(5):3025.
[46] Izquierdo I,Barrachina M N,Hermida-Nogueira L,et al.A comprehensive tyrosine phosphoproteomic analysis reveals novel components of the platelet CLEC-2 signaling cascade[J]. Thromb Haemost,2020,120(2):262-276.
[47] Kumar V.The trinity of cGAS,TLR9,and ALRs guardians of the cellular galaxy against host-derived self-DNA[J]. Front Immunol,2021,11:624597.
[48] Locke M,Francis R J,Tsaousi E,et al.Fibrinogen protects neutrophils from the cytotoxic effects of histones and delays neutrophil extracellular trap formation induced by ionomycin[J]. Sci Rep,2020,10(1): 11694.
[49] Escopy S,Chaikof E L.Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation[J]. Blood Vessel Thromb Hemost,2024,1(3):100015.
[50] Xiong W C,Chai J W,Wu J N,et al.Cathelicidin-HG alleviates sepsis-induced platelet dysfunction by inhibiting GPVI-mediated platelet activation[J]. Research 2024,7:0381.
[51] Fang J H,Ding H G,Huang J Q,et al.Mac-1 blockade impedes adhesion-dependent neutrophil extracellular trap formation and ameliorates lung injury in LPS-induced sepsis[J]. Front Immunol,2025,16:1548913.
[52] Eisen D P,Reid D,Mcbryde E S.Acetyl salicylic acid usage and mortality in critically ill patients with the systemic inflammatory response syndrome and sepsis[J]. Crit Care Med,2012,40(6):1761-1767.
[53] Chen W,Janz D R,Bastarache J A,et al.Prehospital aspirin use is associated with reduced risk of acute respiratory distress syndrome in critically ill patients: a propensity-adjusted analysis[J]. Crit Care Med,2015, 43(4):801-807.
[54] Kiers D,Van Der Heijden W A,Van Ede L,et al. A randomised trial on the effect of anti-platelet therapy on the systemic inflammatory response in human endotoxaemia[J]. Thromb Haemost,2017,117(9):1798-1807.
[55] Mariotti A,Ezzraimi A E,Camoin-Jau L.Effect of antiplatelet agents on Escherichia coli sepsis mechanisms: A review[J]. Front Microbiol,2022,13: 1043334.
[56] Shen X F,Cao K,Zhao Y,et al.Targeting neutrophils in sepsis: from mechanism to translation[J]. Front Pharmacol, 2021,12:644270.
[57] Liu X J,Li T J,Chen H L,et al.Role and intervention of PAD4 in NETs in acute respiratory distress syndrome[J]. Respir Res,2024,25(1):63.
[58] Wu T J,Wang T,Jiang J J,et al.Effect of neutrophil elastase inhibitor (sivelestat sodium) on oxygenation in patients with sepsis-induced acute respiratory distress syndrome[J]. J Inflamm Res,2025,18:4449-4458.
[59] Nandi D,Debnath M,Forster J 3rd,et al. Nanoparticle-mediated co-delivery of inflammasome inhibitors provides protection against sepsis[J]. Nanoscale, 2024,16(9):4678-4690.
[60] Willemsen J F,Wenskus J,Lenz M,et al.DNases improve effectiveness of antibiotic treatment in murine polymicrobial sepsis[J]. Front Immunol,2024,14:1254838.
[61] Shi H,Gandhi A A,Smith S A,et al.Endothelium-protective,histone-neutralizing properties of the polyanionic agent defibrotide[J]. JCI Insight,2021,6(17): e149149.
[62] Kumar S V R,Kulkarni O P,Mulay S R,et al. Neutrophil extracellular trap-related extracellular histones cause vascular necrosis in severe GN[J]. J Am Soc Nephrol, 2015,26(10):2399-2413.
[63] He S J,Fan C Y,Ma J,et al.Platelet transfusion in patients with sepsis and thrombocytopenia: a propensity score-matched analysis using a large ICU database[J]. Front Med,2022,9:830177.
[64] Zhou W,Fan C Y,He S J,et al.Impact of platelet transfusion thresholds on outcomes of patients with sepsis: analysis of the MIMIC-IV database[J]. Shock, 2022,57(4):486-493.
[65] Chu Y X,Guo H,Zhang Y C,et al.Procoagulant platelets: Generation,characteristics,and therapeutic target[J]. J Clin Lab Anal,2021,35(5):e23750.

血小板-中性粒细胞相互作用在脓毒症免疫血栓形成中的研究进展^*

Research Progress on the Interaction between Platelets and Neutrophils in Immunothrombosis during Sepsis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

关于本刊

作者中心

在线期刊

访问统计

联系我们

[1]	施艺璇, 何苏英. 血小板抗体检测临床应用情况分析[J]. 临床输血与检验, 2026, 28(2): 178-184.
[2]	严仲文, 林栋, 陈宝婵, 叶群弟, 曹芷茗, 陈丽妮, 聂成利, 付昕, 张伟龙, 黄志森. 高频率单采血小板捐献者骨代谢标志物变化及骨密度分析^*[J]. 临床输血与检验, 2026, 28(2): 221-226.
[3]	刘艺, 魏婷, 李庆山. 免疫性血小板减少症患者中血小板抗体检测的研究进展^*[J]. 临床输血与检验, 2026, 28(2): 273-279.
[4]	王欣, 李峣, 单卓越, 赵丽艳. CD36抗原缺失与临床输血安全相关研究进展^*[J]. 临床输血与检验, 2026, 28(2): 279-285.
[5]	周载鑫, 钱宝华, 顾海慧. 化疗诱导血小板减少的机制及防治措施的研究进展^*[J]. 临床输血与检验, 2026, 28(2): 293-299.
[6]	李健, 赵燕, 许静静, 孙悦, 徐佟, 常洪劲. PRP对人子宫内膜基质细胞增殖和迁移的影响及关键基因CDCA8的筛选^*[J]. 临床输血与检验, 2026, 28(1): 44-51.
[7]	刘雯, 王文星, 范娜, 陈伟, 梁静. Th17/Treg平衡及细胞因子水平与血小板输注无效的相关性研究^*[J]. 临床输血与检验, 2026, 28(1): 65-69.
[8]	何盈, 冯文秋, 秦萍, 朱培元. 银杏内酯B调控血小板活化分子机制的研究进展^*[J]. 临床输血与检验, 2026, 28(1): 146-152.
[9]	李津杞, 秦爱华, 任瑜菲, 唐河山, 陈翠敏, 钱宝华, 臧艳. 氢气抑制单采血小板活化和凋亡的作用研究^*[J]. 临床输血与检验, 2025, 27(6): 775-782.
[10]	谢文举, 付子可, 王秋实. 胎儿/新生儿同种免疫性血小板减少症研究进展^*[J]. 临床输血与检验, 2025, 27(6): 882-888.
[11]	蔡晓红, 雷航, 王学锋. 2025年AABB和ICTMG国际临床实践指南——《血小板输注指南》和要点解读^*[J]. 临床输血与检验, 2025, 27(5): 577-584.
[12]	侯晓宇, 夏文军, 陈睿驰, 孙登莲, 吴煌, 文爱清. METTL3介导ITGB3的m⁶A甲基化修饰促进巨核细胞分化^*[J]. 临床输血与检验, 2025, 27(5): 594-603.
[13]	马静斯, 赵宁, 邓江, 张艳宇. 血小板中细菌病原体检测技术的进展^*[J]. 临床输血与检验, 2025, 27(5): 667-673.
[14]	李娇, 李剑平, 李晓丰. 冷冻储存对血小板结构和功能影响的研究进展^*[J]. 临床输血与检验, 2025, 27(5): 695-700.
[15]	王嘉欣, 王海莹, 陈立力, 黄永莉, 李卓豫, 邢颜超, 张进进. 血源性滴眼液治疗干眼症的临床应用进展[J]. 临床输血与检验, 2025, 27(5): 717-726.