Mechanism of action of mitochondrial DNA in trauma

doi:10.3877/cma.j.issn.2096-1537.2020.04.005

Abstract

Abstract:

Trauma is the most direct form of organ and tissue damage and one of the leading causes of death and disability in the world. Secondary tissue damage can be caused by ischemia-reperfusion, acidosis, hypoxemia, surgery, hemorrhage and massive blood transfusion associated with trauma. Trauma releases a large number of endogenous damage-associated molecular patterns (DAMPs), triggers systemic inflammatory response syndrome (SIRS), sepsis, multiple organ failure, and even death. Recent studies have shown that mitochondrial-derived DAMPs such as mitochondrial DNA (mtDNA) play an important role in the inflammatory response. The release of mtDNA induces an immune response, exacerbates the inflammatory responseand causes damage to tissues and organs. This review focuses on the release mechanism and the signaling pathways of mtDNA, the relationship between mtDNA and the prognosis of trauma and therapeutic strategies for release of mtDNA intrauma.

Key words: Mitochondrial DNA, Signaling pathway, Trauma, Inflammation

Xuanheng Li, Xiuwen Wu, Jian′an Ren. Mechanism of action of mitochondrial DNA in trauma[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2020, 06(04): 374-378.

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URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2020.04.005

https://icu.cma-cmc.com.cn/EN/Y2020/V06/I04/374

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References 43

1	Huber-Lang M, Lambris JD, Ward PA. Innate immune responses to trauma [J]. Nat Immunol, 2018, 19(4): 327-341.
2	Vourc'h M, Roquilly A, Asehnoune K. Trauma-induced damage-associated molecular patterns-mediated remote organ injury and immunosuppression in the acutely ill patient [J]. Front Immunol, 2018, 9: 1330.
3	Lord JM, Midwinter MJ, Chen YF, et al. The systemic immune response to trauma: an overview of pathophysiology and treatment [J]. Lancet, 2014, 384(9952): 1455-1465.
4	康焰, 唐之韵. 重症创伤:重症医学有不可替代的作用 [J/OL]. 中华重症医学电子杂志, 2016, 2(1): 26-31.
5	Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury [J]. Nature, 2010, 464(7285): 104-107.
6	West AP, Shadel GS. Mitochondrial DNA in innate immune responses and inflammatory pathology [J]. Nat Rev Immunol, 2017, 17(6): 363-375.
7	Shadel GS, Horvath TL. Mitochondrial ROS signaling in organismal homeostasis [J]. Cell, 2015, 163(3): 560-569.
8	Weinberg SE, Sena LA, Chandel NS. Mitochondria in the regulation of innate and adaptive immunity [J]. Immunity, 2015, 42(3): 406-417.
9	Rock KL, Kono H. The inflammatory response to cell death [J]. Annu Rev Pathol, 2008, 3(1): 99-126.
10	Brenner C, Galluzzi L, Kepp O, et al. Decoding cell death signals in liver inflammation [J]. J Hepatol, 2013, 59(3): 583-594.
11	Simmons JD, Lee YL, Mulekar S, et al. Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects [J]. Ann Surg, 2013, 258(4): 591-598.
12	Gu X, Yao Y, Wu G, et al. The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome [J]. PLoS One, 2013, 8(8): e72834.
13	Mcilroy DJ, Minahan K, Keely S, et al. Reduced deoxyribonuclease enzyme activity in response to high postinjury mitochondrial DNA concentration provides a therapeutic target for Systemic Inflammatory Response Syndrome [J]. J Trauma Acute Care Surg, 2018, 85(2): 354-358.
14	Skulachev VP. Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms [J]. Mol Aspects Med, 1999, 20(3): 139-184.
15	Yue R, Xia X, Jiang J, et al. Mitochondrial DNA oxidative damage contributes to cardiomyocyte ischemia/reperfusion-injury in rats: cardioprotective role of lycopene [J]. J Cell Physiol, 2015, 230(9): 2128-2141.
16	Wang XR, Ding R, Tao TQ, et al. Myofibrillogenesis regulator 1 rescues renal ischemia/reperfusion injury by recruitment of PI3K-dependent P-AKT to mitochondria [J]. Shock, 2016, 46(5): 531-540.
17	Caielli S, Athale S, Domic B, et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus [J]. J Exp Med, 2016, 213(5): 697-713.
18	Shimada K, Crother TR, Karlin J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis [J]. Immunity, 2012, 36(3): 401-414.
19	György B, Szabó TG, Pásztói M, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles [J]. Cell Mol Life Sci, 2011, 68(16): 2667-2688.
20	Boudreau LH, Duchez AC, Cloutier N, et al. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation [J]. Blood, 2014, 124(14): 2173-2183.
21	Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria [J]. Science, 2004, 303(5663): 1532-1535.
22	Mcilroy DJ, Bigland M, White AE, et al. Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery [J]. J Trauma Acute Care Surg, 2015, 78(2): 282-288.
23	Liu L, Mao Y, Xu B, et al. Induction of neutrophil extracellular traps during tissue injury: involvement of STING and toll-like receptor 9 pathways [J]. Cell Prolif, 2019, 52(3): e12579.
24	Barbalat R, Ewald SE, Mouchess ML, et al. Nucleic acid recognition by the innate immune system [J]. Annu Rev Immunol, 2011, 29(1): 185-214.
25	Wei X, Shao B, He Z, et al. Cationic nanocarriers induce cell necrosis through impairment of Na⁺/K⁺-ATPase and cause subsequent inflammatory response [J]. Cell Res, 2015, 25(2): 237-253.
26	Guo H, Callaway JB, Ting JPY. Inflammasomes: mechanism of action, role in disease, and therapeutics [J]. Nat Med, 2015, 21(7): 677-687.
27	Baroja-Mazo A, Martín-Sánchez F, Gomez AI, et al. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response [J]. Nat Immunol, 2014, 15(8): 738-748.
28	Chen Q, Sun L, Chen ZJ. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing [J]. Nat Immunol, 2016, 17(10): 1142-1149.
29	Gao D, Wu J, Wu YT, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses [J]. Science, 2013, 341(6148): 903-906.
30	Yamanouchi S, Kudo D, Yamada M, et al. Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: time course and the association with clinical status [J]. J Crit Care, 2013, 28(6): 1027-1031.
31	Aswani A, Manson J, Itagaki K, et al. Scavenging circulating mitochondrial DNA as a potential therapeutic option for multiple organ dysfunction in trauma hemorrhage [J]. Front Immunol, 2018, 9: 891.
32	Hu Q, Ren J, Wu J, et al. Elevated levels of plasma mitochondrial DNA are associated with clinical outcome in intra-abdominal infections caused by severe trauma [J]. Surg Infect (Larchmt), 2017, 18(5): 610-618.
33	Sursal T, Stearns-Kurosawa DJ, Itagaki K, et al. Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates [J]. Shock, 2013, 39(1): 55-62.
34	Martinez-Quinones PA, Mccarthy CG, Mentzer CJ, et al. Peritoneal cavity lavage reduces the presence of mitochondrial damage associated molecular patterns in open abdomen patients [J]. J Trauma Acute Care Surg, 2017, 83(6): 1062-1065.
35	Gan L, Zhong J, Zhang R, et al. The immediate intramedullary nailing surgery increased the mitochondrial DNA release that aggravated systemic inflammatory response and lung injury induced by elderly hip fracture [J]. Mediators Inflamm, 2015, 2015: 587378.
36	Jiménez-Alcázar M, Rangaswamy C, Panda R, et al. Host DNases prevent vascular occlusion by neutrophil extracellular traps [J]. Science, 2017, 358(6367): 1202-1206.
37	Mai SHC, Khan M, Dwivedi DJ, et al. Delayed but not early treatment with DNase reduces organ damage and improves outcome in a murine model of sepsis [J]. Shock, 2015, 44(2): 166-172.
38	Wang S, Xie T, Sun S, et al. DNase-1 treatment exerts protective effects in a rat model of intestinal ischemia-reperfusion injury [J]. Sci Rep, 2018, 8(1): 17788.
39	Yang XM, Cui L, White J, et al. Mitochondrially targeted endonuclease Ⅲ has a powerful anti-infarct effect in an in vivo rat model of myocardial ischemia/reperfusion [J]. Basic Res Cardiol, 2015, 110(2): 3.
40	Ma Q, Chen S, Hu Q, et al. NLRP3 inflammasome contributes to inflammation after intracerebral hemorrhage [J]. Ann Neurol, 2014, 75(2): 209-219.
41	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.
42	Hu Q, Ren J, Li G, et al. The mitochondrially targeted antioxidant MitoQ protects the intestinal barrier by ameliorating mitochondrial DNA damage via the Nrf2/ARE signaling pathway [J]. Cell Death Dis, 2018, 9(3): 403.
43	Xin G, Wei Z, Ji C, et al. Metformin uniquely prevents thrombosis by inhibiting platelet activation and mtDNA release [J]. Sci Rep, 2016, 6(1): 36222.

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