巨噬细胞极化在脓毒症免疫机制中的作用
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摘要
脓毒症是由于感染引起的免疫功能失调,最终导致的多脏器功能障碍综合征。巨噬细胞作为先天性免疫和适应性免疫的重要组成成分之一,当微环境变化时,可分化成具有不同功能的表型,称为巨噬细胞极化。巨噬细胞极化在脓毒症的免疫调节中发挥重要作用,调控巨噬细胞极化有望成为未来脓毒症治疗的新靶点。因此,本文就巨噬细胞极化及其在脓毒症免疫机制中的作用进行综述。
Sepsis is a syndrome of immune response caused by infection, resulting in multiple organ dysfunction. Macrophages, as one of the important components of innate and adaptive immunity, can differentiate into phenotypes with different functions when the microenvironment changes which is called macrophage polarization. Macrophage polarization plays an important role in the immunoregulation of sepsis.The regulation of macrophage polarization is expected to be one of the new targets for the treatment of sepsis in the future. Therefore, we review the role of macrophage polarization and its underlying mechanisms in the immunoregulation of sepsis.
Sepsis is a syndrome of immune response caused by infection, resulting in multiple organ dysfunction. Macrophages, as one of the important components of innate and adaptive immunity, can differentiate into phenotypes with different functions when the microenvironment changes which is called macrophage polarization. Macrophage polarization plays an important role in the immunoregulation of sepsis.The regulation of macrophage polarization is expected to be one of the new targets for the treatment of sepsis in the future. Therefore, we review the role of macrophage polarization and its underlying mechanisms in the immunoregulation of sepsis.
引文
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2 Van Der Poll T,Van De Veerdonk FL,Scicluna BP,et al.The immunopathology of sepsis and potential therapeutic targets[J].Nat Rev Immunol,2017,17(7):407-420.
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26 Pena OM,Pistolic J,Raj D,et al.Endotoxin tolerance represents a distinctive state of alternative polarization(M2)in human mononuclear cells[J].J Immunol,2011,186(12):7243-7254.
27 Xu G,Feng L,Song P,et al.Isomeranzin suppresses inflammation by inhibiting M1 macrophage polarization through the NF-kappaB and ERK pathway[J].Int Immunopharmacol,2016,38:175-185.
28 Shu B,Feng Y,Gui Y,et al.Blockade of CD38 diminishes lipopolysaccharide-induced macrophage classical activation and acute kidney injury involving NF-kappaB signaling suppression[J].Cell Signal,2018,42:249-258.
29 Singh P,Dejager L,Amand M,et al.DUSP3 genetic deletion confers M2-like macrophage-dependent tolerance to septic shock[J].J Immunol,2015,194(10):4951-4962.
30 Tang H,Liang YB,Chen ZB,et al.Soluble egg antigen activates M2macrophages via the STAT6 and PI3K pathways,and schistosoma japonicum alternatively activates macrophage polarization to improve the survival rate of septic mice[J].J Cell Biochem,2017,118(12):4230-4239.
31 Song Y,Dou H,Li X,et al.Exosomal miR-146a contributes to the enhanced therapeutic efficacy of interleukin-1beta-primed mesenchymal stem cells against sepsis[J].Stem Cells,2017,35(5):1208-1221.
32 Xia H,Chen L,Liu H,et al.Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype[J].Sci Rep,2017,7(1):99.
33 Li X,Mu G,Song C,et al.Role of M2 macrophages in sepsis-induced acute kidney injury[J].Shock,2018,50(2):233-239.
34 Venet F,Rimmele T,Monneret G.Management of sepsis-induced immunosuppression[J].Crit Care Clin,2018,34(1):97-106.
2 Van Der Poll T,Van De Veerdonk FL,Scicluna BP,et al.The immunopathology of sepsis and potential therapeutic targets[J].Nat Rev Immunol,2017,17(7):407-420.
3 Biswas SK,Chittezhath M,Shalova IN,et al.Macrophage polarization and plasticity in health and disease[J].Immunol Res,2012,53(1-3):11-24.
4 Sica A,Erreni M,Allavena P,et al.Macrophage polarization in pathology[J].Cell Mol Life Sci,2015,72(21):4111-4126.
5 Liu YC,Zou XB,Chai YF,et al.Macrophage polarization in inflammatory diseases[J].Int J Biol Sci,2014,10(5):520-529.
6 Malyshev I,Malyshev Y.Current concept and update of the macrophage plasticity concept:intracellular mechanisms of reprogramming and M3 macrophage″switch″phenotype[J].Biomed Res Int,2015,2015:341308.
7 Labonte AC,Tosello-Trampont AC,Hahn YS.The role of macrophage polarization in infectious and inflammatory diseases[J].Mol Cells,2014,37(4):275-285.
8 Arora S,Dev K,Agarwal B,et al.Macrophages:Their role,activation and polarization in pulmonary diseases[J].Immunobiology,2017,223(4-5):383-396.
9 Wilson HM.SOCS proteins in macrophage polarization and function[J].Front Immunol,2014,5:357.
10 Croasdell A,Duffney PF,Kim N,et al.PPARgamma and the innate immune system mediate the resolution of inflammation[J].PPAR Res,2015,2015:549691.
11 Odegaard JI,Ricardo-Gonzalez RR,Goforth MH,et al.Macrophagespecific PPARgamma controls alternative activation and improves insulin resistance[J].Nature,2007,447(7148):1116-1120.
12 Szanto A,Balint BL,Nagy ZS,et al.STAT6 transcription factor is a facilitator of the nuclear receptor PPARgamma-regulated gene expression in macrophages and dendritic cells[J].Immunity,2010,33(5):699-712.
13 Liao X,Sharma N,Kapadia F,et al.Kruppel-like factor 4 regulates macrophage polarization[J].J Clin Invest,2011,121(7):2736-2749.
14 Zhou D,Huang C,Lin Z,et al.Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways[J].Cell Signal,2014,26(2):192-197.
15 Luyendyk JP,Schabbauer GA,Tencati M,et al.Genetic analysis of the role of the PI3K-Akt pathway in lipopolysaccharide-induced cytokine and tissue factor gene expression in monocytes/macrophages[J].J Immunol,2008,180(6):4218-4226.
16 Arranz A,Doxaki C,Vergadi E,et al.Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization[J].Proc Natl Acad Sci U S A,2012,109(24):9517-9522.
17 Krausgruber T,Blazek K,Smallie T,et al.IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses[J].Nat Immunol,2011,12(3):231-238.
18 Eguchi J,Kong X,Tenta M,et al.Interferon regulatory factor4 regulates obesity-induced inflammation through regulation of adipose tissue macrophage polarization[J].Diabetes,2013,62(10):3394-3403.
19 Takeuch O,Akira S.Epigenetic control of macrophage polarization[J].Eur J Immunol,2011,41(9):2490-2493.
20 Ishii M,Wen H,Corsa CA,et al.Epigenetic regulation of the alternatively activated macrophage phenotype[J].Blood,2009,114(15):3244-3254.
21 Satoh T,Takeuchi O,Vandenbon A,et al.The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection[J].Nat Immunol,2010,11(10):936-944.
22 Essandoh K,Li Y,Huo J,et al.MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response[J].Shock,2016,46(2):122-131.
23 Ying H,Kang Y,Zhang H,et al.MiR-127 modulates macrophage polarization and promotes lung inflammation and injury by activating the JNK pathway[J].J Immunol,2015,194(3):1239-1251.
24 Banerjee S,Xie N,Cui H,et al.MicroRNA let-7c regulates macrophage polarization[J].J Immunol,2013,190(12):6542-6549.
25 Porta C,Rimoldi M,Raes G,et al.Tolerance and M2(alternative)macrophage polarization are related processes orchestrated by p50nuclear factor kappaB[J].Proc Natl Acad Sci U S A,2009,106(35):14978-14983.
26 Pena OM,Pistolic J,Raj D,et al.Endotoxin tolerance represents a distinctive state of alternative polarization(M2)in human mononuclear cells[J].J Immunol,2011,186(12):7243-7254.
27 Xu G,Feng L,Song P,et al.Isomeranzin suppresses inflammation by inhibiting M1 macrophage polarization through the NF-kappaB and ERK pathway[J].Int Immunopharmacol,2016,38:175-185.
28 Shu B,Feng Y,Gui Y,et al.Blockade of CD38 diminishes lipopolysaccharide-induced macrophage classical activation and acute kidney injury involving NF-kappaB signaling suppression[J].Cell Signal,2018,42:249-258.
29 Singh P,Dejager L,Amand M,et al.DUSP3 genetic deletion confers M2-like macrophage-dependent tolerance to septic shock[J].J Immunol,2015,194(10):4951-4962.
30 Tang H,Liang YB,Chen ZB,et al.Soluble egg antigen activates M2macrophages via the STAT6 and PI3K pathways,and schistosoma japonicum alternatively activates macrophage polarization to improve the survival rate of septic mice[J].J Cell Biochem,2017,118(12):4230-4239.
31 Song Y,Dou H,Li X,et al.Exosomal miR-146a contributes to the enhanced therapeutic efficacy of interleukin-1beta-primed mesenchymal stem cells against sepsis[J].Stem Cells,2017,35(5):1208-1221.
32 Xia H,Chen L,Liu H,et al.Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype[J].Sci Rep,2017,7(1):99.
33 Li X,Mu G,Song C,et al.Role of M2 macrophages in sepsis-induced acute kidney injury[J].Shock,2018,50(2):233-239.
34 Venet F,Rimmele T,Monneret G.Management of sepsis-induced immunosuppression[J].Crit Care Clin,2018,34(1):97-106.