[1]罗何娇,邓烈华,张媛莉.精氨酸酶1调控中性粒细胞功能在脓毒症免疫抑制中的作用及机制研究进展[J].陕西医学杂志,2025,54(9):1270-1274.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.021]
 LUO Hejiao,DENG Liehua,ZHANG Yuanli.Research progress on role and mechanism of arginase 1 in sepsis-induced immunosuppression by regulating neutrophil function[J].,2025,54(9):1270-1274.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.021]
点击复制

精氨酸酶1调控中性粒细胞功能在脓毒症免疫抑制中的作用及机制研究进展

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年9期
页码:
1270-1274
栏目:
综 述
出版日期:
2025-09-05

文章信息/Info

Title:
Research progress on role and mechanism of arginase 1 in sepsis-induced immunosuppression by regulating neutrophil function
作者:
罗何娇邓烈华张媛莉
(广东医科大学附属医院重症医学科,广东 湛江 524000)
Author(s):
LUO HejiaoDENG LiehuaZHANG Yuanli
(Department of Critical Care Medicine,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524000,China)
关键词:
脓毒症精氨酸酶1中性粒细胞免疫抑制免疫功能分子机制
Keywords:
SepsisArginase 1NeutrophilImmunosuppressionImmune functionMolecular mechanism
分类号:
R 459.7
DOI:
DOI:10.3969/j.issn.1000-7377.2025.09.021
文献标志码:
A
摘要:
脓毒症是由宿主感染应答失调引发的临床综合征,以早期过度炎症与后期免疫抑制为特征,中性粒细胞在此过程中发挥至关重要的作用。精氨酸酶1(Arg-1)作为一种在免疫调节和代谢过程中发挥关键作用的酶,在脓毒症血浆及中性粒细胞中的表达和活性发生显著变化,能够调控中性粒细胞功能,共同介导脓毒症免疫抑制。但目前关于这方面的研究较少,具体机制尚未阐明。现对Arg-1在脓毒症炎症与免疫调节中的作用、Arg-1在中性粒细胞中的表达调控及其对中性粒细胞功能的影响以及相关分子机制研究进展进行系统综述,为深入理解Arg-1在脓毒症免疫抑制中的作用提供参考,为脓毒症的治疗提供新的思路和方向。
Abstract:
Sepsis is a clinical syndrome triggered by dysregulation of the host’s response to infection,characterized by early hyperinflammation and late immunosuppression,in which neutrophils play a key role.Arginase 1 (Arg-1),an enzyme that plays a key role in immunomodulation and metabolism,is significantly altered in expression and activity in sepsis plasma as well as in neutrophils,and is able to modulate neutrophil function,which collectively mediates sepsis immunosuppression.But few studies have been conducted in this area,and the specific mechanisms have not yet been elucidated.This article systematically reviews the research progress of the role of Arg-1 in inflammation and immune regulation in sepsis,the expression regulation of Arg-1 in neutrophils and its effect on neutrophil function,and the related molecular mechanisms,so as to provide a reference for further understanding the role of Arg-1 in immunosuppression in sepsis,and provide new ideas and directions for the treatment of sepsis.

参考文献/References:

[1]ZHU C L,YAO R Q,LI L X,et al.Mechanism of mitophagy and its role in sepsis induced organ dysfunction:A review[J].Front Cell Dev Biol,2021,9:664896.
[2]ALMALKI W H.The sepsis induced defective aggravation of immune cells:A translational science underling chemico-biological interactions from altered bioenergetics and/or cellular metabolism to organ dysfunction[J].Mol Cell Biochem,2021,476(6):2337-2344.
[3]WEN R,LIU Y P,TONG X X,et al.Molecular mechanisms and functions of pyroptosis in sepsis and sepsis-associated organ dysfunction[J].Front Cell Infect Microbiol,2022,12:962139.
[4]ZENG R,ZHENG Y,FAN R,et al.Si-ni-tang (a Chinese herbal formula) for improving immunofunction in sepsis:Study protocol for a pilot randomized controlled trial[J].Trials,2019,20(1):537.
[5]WANG Y,ZHU C L,LI P,et al.The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome[J].Front Immunol,2023,14:1112196.
[6]PAN T,SUN S,CHEN Y,et al.Immune effects of PI3K/Akt/HIF-1alpha-regulated glycolysis in polymorphonuclear neutrophils during sepsis[J].Crit Care,2022,26(1):29.
[7]ZOU S,JIE H,HAN X,et al.The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury[J].Int Immunopharmacol,2023,124(Pt A):110436.
[8]吴泽华,李跃东,戴莹莹,等.降钙素原、C反应蛋白、白细胞计数和中性粒细胞比率在重症医学科脓毒症治疗预后判断中的临床价值[J].陕西医学杂志,2024,53(4):540-543.
[9]CHEN Z,ZHANG H,QU M,et al.Review:The emerging role of neutrophil extracellular traps in sepsis and sepsis-associated thrombosis[J].Front Cell Infect Microbiol,2021,11:653228.
[10]MURATA K,MURAO A,AZIZ M,et al.Extracellular CIRP induces novel nectin-2+ (CD112+) neutrophils to promote th1 differentiation in sepsis[J].J Immunol,2023,210(3):310-321.
[11]ZHANG H,WU D,WANG Y,et al.Ferritin-mediated neutrophil extracellular traps formation and cytokine storm via macrophage scavenger receptor in sepsis-associated lung injury[J].Cell Commun Signal,2024,22(1):97.
[12]CLEMENTE G S,VAN WAARDE A,ANTUNES I F,et al.Arginase as a potential biomarker of disease progression:A molecular imaging perspective[J].Int J Mol Sci,2020,21(15):5291.
[13]DERAKHSHANI A,HEMMAT N,ASADZADEH Z,et al.Arginase 1 (Arg1) as an up-regulated gene in COVID-19 patients:A promising marker in COVID-19 Immunopathy[J].J Clin Med,2021,10(5):1051.
[14]YIN X Y,LIU Y,LU Z M,et al.LncRNA NEAT-2 regulate the function of endothelial progenitor cells in experimental sepsis model[J].Mol Biol Rep,2023,50(8):6643-6654.
[15]MONTICELLI L A,BUCK M D,FLAMAR A L,et al.Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation[J].Nat Immunol,2016,17(6):656-665.
[16]DIALLO K,SIMONS N,SAYEGH S,et al.Evidence for tmTNF reverse signaling in vivo:Implications for an arginase-1-mediated therapeutic effect of TNF inhibitors during inflammation[J].iScience,2021,24(4):102331.
[17]QIN W,ZHANG J,LV W,et al.Effect of carbon monoxide-releasing molecules Ⅱ-liberated CO on suppressing inflammatory response in sepsis by interfering with nuclear factor kappa B activation[J].PLoS One,2013,8(10):e75840.
[18]HARA M,TORISU K,TOMITA K,et al.Arginase 2 is a mediator of ischemia-reperfusion injury in the kidney through regulation of nitrosative stress[J].Kidney Int,2020,98(3):673-685.
[19]DARCY C J,MINIGO G,PIERA K A,et al.Neutrophils with myeloid derived suppressor function deplete arginine and constrain T cell function in septic shock patients[J].Crit Care,2014,18(4):R163.
[20]DAI X K,DING Z X,TAN Y Y,et al.Neutrophils inhibit CD8+ T cells immune response by arginase-1 signaling in patients with sepsis[J].World J Emerg Med,2022,13(4):266-273.
[21]VONWIRTH V,BULBUL Y,WERNER A,et al.Inhibition of arginase 1 liberates potent T cell immunostimulatory activity of human neutrophil granulocytes[J].Front Immunol,2020,11:617699.
[22]GEIGER R,RIECKMANN J C,WOLF T,et al.L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity[J].Cell,2016,167(3):829-842.e13.
[23]WEST E E,MERLE N S,KAMINSKI M M,et al.Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection[J].Immunity,2023,56(9):2036-2053.e12.
[24]祝筱梅,张卉,姚咏明.论脓毒症免疫调理策略的转化应用[J].中国急救医学,2023,43(11):862-867.
[25]STEGGERDA S M,BENNETT M K,CHEN J,et al.Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment[J].J Immunother Cancer,2017,5(1):101.
[26]UHEL F,AZZAOUI I,GREGOIRE M,et al.Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis[J].Am J Respir Crit Care Med,2017,196(3):315-327.
[27]TIAN L X,TANG X,ZHU J Y,et al.Cytochrome P450 1A1 enhances arginase-1 expression,which reduces LPS-induced mouse peritonitis by targeting JAK1/STAT6[J].Cell Immunol,2020,349:104047.
[28]VAN DEN BOSSCHE J,LAMERS W H,KOEHLER E S,et al.Pivotal advance:Arginase-1-independent polyamine production stimulates the expression of IL-4-induced alternatively activated macrophage markers while inhibiting LPS-induced expression of inflammatory genes[J].J Leukoc Biol,2012,91(5):685-699.
[29]MUNDER M.Arginase:An emerging key player in the mammalian immune system[J].Br J Pharmacol,2009,158(3):638-651.
[30]DWIVEDI A,UI MHAONAIGH A,CARROLL M,et al.Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19[J].JCI Insight,2024,9(17) :e171659.
[31]MAHDI A,KOVAMEES O,PERNOW J.Improvement in endothelial function in cardiovascular disease-Is arginase the target?[J].Int J Cardiol,2020,301:207-214.
[32]LONG X,LI X,LI T,et al.Umbilical cord mesenchymal stem cells enhance the therapeutic effect of imipenem by regulating myeloid-derived suppressor cells in septic mice[J].Ann Transl Med,2021,9(5):404.
[33]PISTORIUS K,LY L,SOUZA P R,et al.MCTR3 reprograms arthritic monocytes to upregulate arginase-1 and exert pro-resolving and tissue-protective functions in experimental arthritis[J].EBioMedicine,2022,79:103974.
[34]ZHANG H,ZHU X,FRIESEN T J,et al.Annexin A2/TLR2/MYD88 pathway induces arginase 1 expression in tumor-associated neutrophils[J].J Clin Invest,2022,132(22):e153643.
[35]CAI W,DAI X,CHEN J,et al.STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice[J].JCI Insight,2019,4(20):e131355.
[36]SYMOWSKI C,VOEHRINGER D.Th2 cell-derived IL-4/IL-13 promote ILC2 accumulation in the lung by ILC2-intrinsic STAT6 signaling in mice[J].Eur J Immunol,2019,49(9):1421-1432.
[37]RUSSKAMP D,AGUILAR-PIMENTEL A,ALESSANDRINI F,et al.IL-4 receptor alpha blockade prevents sensitization and alters acute and long-lasting effects of allergen-specific immunotherapy of murine allergic asthma[J].Allergy,2019,74(8):1549-1560.
[38]MONIN L,GRIFFITHS K L,LAM W Y,et al.Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis[J].J Clin Invest,2015,125(12):4699-4713.
[39]MARGAROLI C,CARDENAS M A,JANSEN C S,et al.The immunosuppressive phenotype of tumor-infiltrating neutrophils is associated with obesity in kidney cancer patients[J].Oncoimmunology,2020,9(1):1747731.
[40]SANTIAGO-OLIVARES C,RIVERA-TOLEDO E,GOMEZ B.Nitric oxide production is downregulated during respiratory syncytial virus persistence by constitutive expression of arginase 1[J].Arch Virol,2019,164(9):2231-2241.
[41]LIANG Y,YI P,YUAN D M K,et al.IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis[J].Cell Mol Immunol,2019,16(2):126-137.
[42]GILMORE S P,GONYE A L K,LI E C,et al.Effects of a novel microtubule-depolymerizer on pro-inflammatory signaling in RAW264.7 macrophages[J].Chem Biol Interact,2018,280:109-116.
[43]BAIER J,GANSBAUER M,GIESSLER C,et al.Arginase impedes the resolution of colitis by altering the microbiome and metabolome[J].J Clin Invest,2020,130(11):5703-5720.
[44]STOERMER K A,BURRACK A,OKO L,et al.Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus[J].J Immunol,2012,189(8):4047-4059.
[45]HAYDAR D,GONZALEZ R,GARVY B A,et al.Myeloid arginase-1 controls excessive inflammation and modulates T cell responses in pseudomonas aeruginosa pneumonia[J].Immunobiology,2021,226(1):152034.
[46]GUPTA S,KAPLAN M J.The role of neutrophils and NETosis in autoimmune and renal diseases[J].Nat Rev Nephrol,2016,12(7):402-413.
[47]XIAO M,ZHOU J,ZHANG W,et al.Association of immunosuppressive CD45+CD33+CD14CD10HLA-DR-/low neutrophils with poor prognosis in patients with lymphoma and their expansion and activation through STAT3/arginase-1 pathway in vitro[J].Cytojournal,2024,21:69.
[48]YAIW K C,MOHAMMAD A A,TAHER C,et al.Human cytomegalovirus induces upregulation of arginase Ⅱ:Possible implications for vasculopathies[J].Basic Res Cardiol,2014,109(2):401.
[49]WANG X,XIANG H,TOYOSHIMA Y,et al.Arginase-1 inhibition reduces migration ability and metastatic colonization of colon cancer cells[J].Cancer Metab,2023,11(1):1.

相似文献/References:

[1]李文军,于代华,宗 雷,等.脾多肽注射液对脓毒症患者血清炎症因子及免疫功能的影响*[J].陕西医学杂志,2019,(4):463.
 LI Wenjun,YU Daihua,ZONG Lei,et al.Effect of spleen peptide injection on serum inflammatory factors and immune function in patients With Sepsis[J].,2019,(9):463.
[2]商跃云,张 慧,林书祥,等.脓毒症患儿外周血CD4+T细胞Bip、ATF6及DDIT3表达水平变化[J].陕西医学杂志,2019,(6):706.
 SHSNG Yueyun,ZHANG Hui,LIN Shuxiang,et al.Changes of immunoglobulin binding protein, activating transcription factor 6 and DNA-damage-inducible transcript 3 protein levels in CD4+T cells in children with sepsis[J].,2019,(9):706.
[3]田永超.脓毒症肠黏膜屏障功能障碍防治研究进展[J].陕西医学杂志,2020,49(4):510.
 TIAN Yongchao..Progress in prevention and treatment of intestinal mucosal barrier dysfunction in sepsis[J].,2020,49(9):510.
[4]王 婷,韦小碗,杨 亮,等.脓毒症患者血清PCT、CRP、IL-6 和IL-10水平检测及临床意义[J].陕西医学杂志,2020,49(11):1510.[doi:DOI:10.3969/j.issn.1000-7377.2020.11.037]
 WANG Ting,WEI Xiaowan,YANG Liang,et al.Expression of serum PCT,CRP,IL-6 and IL-10 in patients with sepsis and their clinical diagnostic value[J].,2020,49(9):1510.[doi:DOI:10.3969/j.issn.1000-7377.2020.11.037]
[5]肖武强,董 磊,吴先正△.急性胃肠损伤分级联合D-乳酸、内毒素水平测定对脓毒症患者预后的评估价值*[J].陕西医学杂志,2020,49(12):1577.[doi:DOI:10.3969/j.issn.1000-7377.2020.12.010]
[6]张 瑜,王 娟.脓毒症并发急性呼吸窘迫综合征患者血清血管内皮钙黏蛋白、血管生成素2表达及与预后相关性研究[J].陕西医学杂志,2022,51(2):176.[doi:DOI:10.3969/j.issn.1000-7377.2022.02.011]
 ZHANG Yu,WANG Juan.Expression of serum vascular endothelial cadherin and angiopoietin 2 in sepsis patients complicated with acute respiratory distress syndrome and their correlation with prognosis[J].,2022,51(9):176.[doi:DOI:10.3969/j.issn.1000-7377.2022.02.011]
[7]王兴程,张向宁,侯崇智,等.右美托咪定在脓毒症治疗中的作用及机制研究进展[J].陕西医学杂志,2022,51(3):382.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.028]
 WANG Xingcheng,ZHANG Xiangning,HOU Chongzhi,et al.Research progress on the role and mechanism of dexmedetomidine in the treatment of sepsis[J].,2022,51(9):382.[doi:DOI:10.3969/j.issn.1000-7377.2022.03.028]
[8]梁 红,霍红艳.右美托咪定对盲肠结扎穿孔术诱导的脓毒症大鼠急性肺损伤保护作用及其与磷酸化JAK激酶2/酪氨酸磷酸化通路的关系[J].陕西医学杂志,2023,52(1):12.[doi:DOI:10.3969/j.issn.1000-7377.2023.01.003]
 LIANG Hong,HUO Hongyan.Protective effect of dexmedetomidine on CLP-induced acute lung injury in rats with sepsis and its relationship with JAK2/STAT3 pathway[J].,2023,52(9):12.[doi:DOI:10.3969/j.issn.1000-7377.2023.01.003]
[9]廖崇皓,徐岸楠,李世瑶,等.血清壳多糖酶3样蛋白1和几丁质酶1在脓毒症新生儿中的表达变化及其临床价值研究[J].陕西医学杂志,2024,(3):368.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.017]
 LIAO Chonghao,XU Annan,LI Shiyao,et al.Expression changes of serum chitosinase 3-like protein 1 and chitinase 1 in neonatal sepsis and their clinical value[J].,2024,(9):368.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.017]
[10]吴泽华,李跃东,戴莹莹,等.降钙素原、C反应蛋白、白细胞计数和中性粒细胞比率在重症医学科脓毒症治疗预后判断中的临床价值[J].陕西医学杂志,2024,(4):540.[doi:DOI:10.3969/j.issn.1000-7377.2024.04.023]

备注/Memo

备注/Memo:
国家自然科学基金资助项目(82172148);创新药物上市后临床科研专项课题(WKZX2024CX301205)
更新日期/Last Update: 2025-09-04