中性粒细胞胞外诱捕网在系统性红斑狼疮发病机制中作用的研究进展

doi:10.13481/j.1671-587x.20180437

摘要/Abstract

摘要： 中性粒细胞胞外诱捕网（NETs）是中性粒细胞受到刺激后释放产生的网状物，由DNA骨架、组蛋白、颗粒蛋白和胞浆蛋白组成。NETs可从多方面直接及间接地参与多种自身免疫病，如系统性红斑狼疮（SLE）。SLE患者体内NETs生成过多或（和）清除障碍，而异常数量的NETs是SLE自身抗原和自身抗体的重要来源之一，且与疾病严重程度呈正相关关系。NETs不仅参与自身免疫病的病理过程，且与免疫调节有关，NETs可通过激活NOD样受体家族3（NLRP3）炎性小体、刺激低密度粒细胞（LDG）、促进浆样树突状细胞（pDC）合成高水平α-干扰素（IFN-α）等间接作用共同参与SLE的发病。对NETs的调节可能是SLE的潜在治疗途径之一。本文作者对NETs的形成及其在SLE发病机制中的作用及其潜在的治疗方向等进行综述。

关键词: 中性粒细胞胞外诱捕网, 低密度粒细胞, 系统性红斑狼疮, 浆样树突细胞, NOD样受体家族3

中图分类号:

R593.241

林笑颖, 周明倩, 李海昌. 中性粒细胞胞外诱捕网在系统性红斑狼疮发病机制中作用的研究进展[J]. 吉林大学学报(医学版), 2018, 44(04): 886-890.

参考文献

[1] 蒋秋梅,晏波,苟静,等.系统性红斑狼疮患者中性粒细胞胞外诱捕网水平分析[J].中华风湿病学杂志,2017,21(8):542-546.
[2] Darrah E, Andrade F. NETs:the missing link between cell death and systemic autoimmune diseases[J].Front Immunol,2012,3:428.
[3] Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria[J]. Science, 2004,303(5663):1532-1535.
[4] Fuchs TA, Abed U,Goosmann C, et al. Novel cell death program leads to neutrophil extracellular traps[J]. J Cell Biol, 2007,176(2):231-241.
[5] Stojkov D, Amini P, Oberson K, et al. ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation[J]. J Cell Biol,2017,216(12):4073-4090.
[6] Muãoz LE, Kaplan MJ, Radic M, et al. Editorial:NETosis 2:The excitement continues[J]. Front Immunol,2017,8:1318.
[7] Dieker J, Tel J, Pieterse E, et al. Circulating apoptotic microparticles in systemic lupus erythematosus patients drive the activation of dendritic cell subsets and prime neutrophils for NETosis[J]. Arthritis Rheumatol,2016,68(2):462-472.
[8] Truszewska A, Foroncewicz B, Pączek L. The role and diagnostic value of cell-free DNA in systemic lupus erythematosus[J]. Clin Exp Rheumatol,2017,35(2):330-336.
[9] Wang H, Li T, Chen S, et al. Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-of-concept trial of metformin[J]. Arthritis Rheumatol,2015,67(12):3190-3200.
[10] Lande R, Ganguly D, Facchinetti V, et al. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus[J]. Sci Transl Med, 2011, 3(73):73ra19.
[11] Urban CF, Ermert D, Schmid M, et al. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans[J]. PLoS Pathog,2009,5(10):e100639.
[12] Pieterse E, Hofstra J, Berden J, et al. Acetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus[J]. Clin Exp Immunol, 2015, 179(1):68-74.
[13] Knight JS, Carmona-Rivera C, Kaplan MJ. Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases[J]. Front Immunol, 2012, 3(Suppl):380.
[14] Farrera C, Fadeel B. Macrophage clearance of neutrophil extracellular traps is a silent process[J]. J Immunol,2013,191(5):2647-2656.
[15] Zykova SN, Tveita AA, Rekvig OP. Renal dnase1 enzyme activity and protein expression is selectively shut down in murine and human membranoproliferative lupus nephritis[J]. PLoS One, 2010,5(8):e12096.
[16] Leffler J, Gullstrand B, Jönsen A, et al. Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus[J]. Arthrit Res Ther,2013,15(4):R84.
[17] Yeh TM, Chang HC, Liang CC, et al. Deoxyribonuclease-inhibitory antibodies in systemic lupus erythematosus[J]. Biomed Sci,2003,10(5):544-551.
[18] Hakkim A, Furnrohr BG, Amann K, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis[J]. Proc Natl Acad Sci USA,2010,107(21):9813-9818.
[19] Leffler J, Martin M, Gullstrand B, et al. Neutrophil extracellular traps that are not degraded in systemic lupus erythematosus activate complement exacerbating the disease[J]. J Immunol,2012, 188(7):3522-3531.
[20] Mahajan A, Herrmann M, Muñoz LE. Clearance deficiency and cell death pathways:A model for the pathogenesis of SLE[J]. Front Immunol,2016,7:35.
[21] Kahlenberg JM, Carmonarivera C, Smith CK, et al. Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages[J]. J Immunol, 2013, 190(3):1217-1226.
[22] Villanueva E, Yalavarthi S, Berthier CC, et al. Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus[J]. J Immunol,2011,187(1):538-552.
[23] Denny MF, Yalavarthi S, Zhao W, et al. A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type Ⅰ interferons[J]. J Immunol,2010,184(6):3284-3297.
[24] Giannelou M, Mavragani CP. Cardiovascular disease in systemic lupus erythematosus:A comprehensive update[J]. J Autoimmun,2017,82:1-12.
[25] Carmona-Rivera C, Zhao W, Yalavarthi S, et al. Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2[J]. Ann Rheumat Dis,2015,74(7):1417-1424.
[26] Garcia-Romo GS, Caielli S, Vega B, et al. Netting neutrophils are major inducers of type Ⅰ IFN production in pediatric systemic lupus erythematosus[J]. Sci Transl Med, 2011, 3(73):73ra20.
[27] Jimé nez-Alcázar M, Rangaswamy C, Panda R, et al. Host DNases prevent vascular occlusion by neutrophil extracellular traps[J]. Science,2017,358(6367):1202-1206.
[28] Martínez Valle F, Balada E, Ordi-Ros J, et al. DNase 1 and systemic lupus erythematosus[J]. Autoimmun Rev,2008,7(5):359-363.
[29] Lood C, Blanco LP, Purmalek MM, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease[J]. Nat Med, 2016,22(2):146-153.
[30] Van Avondt K,Fritsch-Stork R, Derksen RH, et al. Ligation of signal inhibitory receptor on leukocytes-1 suppresses the release of neutrophil extracellular traps in systemic lupus erythematosus[J]. PLoS One,2013,8(10):e78459.
[31] Knight JS, Subramanian V, O'Dell AA, et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice[J]. Ann Rheumat Dis,2015,74(12):2199-2206.
[32] Knight JS, Luo W, O'Dell A A, et al. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis[J]. Circulat Res,2014,114(6):947-956.
[33] Remijsen Q, Berghe TV, Wirawan E, et al. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation[J]. Cell Res,2011,21(2):290-304.
[34] Smith CK, Vivekanandan-Giri A, Tang C, et al. Neutrophil extracellular trap-derived enzymes oxidize high-density lipoprotein:An additional proatherogenic mechanism in systemic lupus erythematosus[J]. Arthrit Rheumatol, 2014, 66(9):2532-2544.
[35] Gupta AK, Giaglis S, Hasler P, et al. Efficient neutrophil extracellular trap induction requires mobilization of both intracellular and extracellular calcium pools and is modulated by cyclosporine A[J]. PLoS One,2014,9(5):e97088.
[36] Handono K, Sidarta YO, Pradana BA, et al. Vitamin D prevents endothelial damage induced by increased neutrophil extracellular traps formation in patients with systemic lupus erythematosus[J]. Acta Med Indones, 2014, 46(3):189-198.