Mitochondrial Dysfunction and Immune Cell Metabolism in Sepsis

다국어 초록 (Multilingual Abstract)

Sepsis is a life threatening condition mediated by systemic infection, but also triggered by hemorrhage and trauma. These aresignificant causes of organ injury implicated in morbidity and mortality, as well as post-sepsis complications associated withdysfunction of innate and adaptive immunity. The role of cellular bioenergetics and loss of metabolic plasticity of immune cellsis increasingly emerging in the pathogenesis of sepsis. This review describes mitochondrial biology and metabolic alterations ofimmune cells due to sepsis, as well as indicates plausible therapeutic opportunities.

참고문헌 (Reference)

1 Cheng SC, "mTOR- and HIF-1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity" 3445 : 1250684-, 2014

2 Marshall JC, "Why have clinical trials in sepsis failed?" 20 : 195-203, 2014

3 Krawczyk CM, "Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation" 115 : 4742-4749, 2010

4 Tadie JM, "Toll-like receptor 4 engagement inhibits adenosine 5'-monophosphate-activated protein kinase activation through a high mobility group box 1 protein-dependent mechanism" 18 : 659-668, 2012

5 Sair M, "Tissue oxygenation and perfusion in patients with systemic sepsis" 29 : 1343-1349, 2001

6 Seth A, "The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle" 6 : 236-245, 2007

7 Wang R, "The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation" 35 : 871-882, 2011

8 Haschemi A, "The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism" 15 : 813-826, 2012

9 Singer M, "The role of mitochondrial dysfunction in sepsis- induced multi-organ failure" 5 : 66-72, 2014

10 Dale DC, "The phagocytes: neutrophils and monocytes" 112 : 935-945, 2008

11 Hotchkiss RS, "The pathophysiology and treatment of sepsis" 348 : 138-150, 2003

12 Bosmann M, "The inflammatory response in sepsis" 34 : 129-136, 2013

13 Delano MJ, "The immune system's role in sepsis progression, resolution, and long-term outcome" 274 : 330-353, 2016

14 Martin GS, "The epidemiology of sepsis in the United States from 1979 through 2000" 348 : 1546-1554, 2003

15 Thomas GD, "The biology of nematode- and IL4Rα -dependent murine macrophage polarization in vivo as defined by RNA-Seq and targeted lipidomics" 120 : e93-e104, 2012

16 Hollenbeck PJ, "The axonal transport of mitochondria" 118 : 5411-5419, 2005

17 Frauwirth KA, "The CD28 signaling pathway regulates glucose metabolism" 16 : 769-777, 2002

18 West AP, "TLR signalling augments macrophage bactericidal activity through mitochondrial ROS" 472 : 476-480, 2011

19 Carré JE, "Survival in critical illness is associated with early activation of mitochondrial biogenesis" 182 : 745-751, 2010

20 Rodríguez-Prados JC, "Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation" 185 : 605-614, 2010

21 Ferro TN, "Smoking in trauma patients: the effects on the incidence of sepsis, respiratory failure, organ failure, and mortality" 69 : 308-312, 2010

22 Deutschman CS, "Sepsis: current dogma and new perspectives" 40 : 463-475, 2014

23 Chen Y, "Roles of transcriptional corepressor RIP140 and coactivator PGC-1alpha in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes" 362 : 11-18, 2012

24 Larsen FJ, "Regulation of mitochondrial function and energetics by reactive nitrogen oxides" 53 : 1919-1928, 2012

25 Murray PJ, "Protective and pathogenic functions of macrophage subsets" 11 : 723-737, 2011

26 Gentile LF, "Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care" 72 : 1491-1501, 2012

27 Finck BN, "Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease" 115 : 2540-2548, 2007

28 Boekstegers P, "Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock" 19 : 317-323, 1991

29 Zmijewski JW, "Participation of mitochondrial respiratory complex III in neutrophil activation and lung injury" 296 : L624-L634, 2009

30 Xie M, "PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation" 7 : 13280-, 2016

31 Yang L, "PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis" 5 : 4436-, 2014

32 Vats D, "Oxidative metabolism and PGC-1beta attenuate macrophage- mediated inflammation" 4 : 13-24, 2006

33 Campello S, "Orchestration of lymphocyte chemotaxis by mitochondrial dynamics" 203 : 2879-2886, 2006

34 Huttunen R, "Obesity and smoking are factors associated with poor prognosis in patients with bacteraemia" 7 : 13-, 2007

35 Kolaczkowska E, "Neutrophil recruitment and function in health and inflammation" 13 : 159-175, 2013

36 Link DC, "Neutrophil homeostasis: a new role for stromal cell-derived factor-1" 32 : 169-178, 2005

37 Jha AK, "Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization" 42 : 419-430, 2015

38 Yeung F, "Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase" 23 : 2369-2380, 2004

39 Zmijewski JW, "Mitochondrial respiratory complex I regulates neutrophil activation and severity of lung injury" 178 : 168-179, 2008

40 van Raam BJ, "Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation" 3 : e2013-, 2008

41 Desai SP, "Mitochondrial localization and the persistent migration of epithelial cancer cells" 104 : 2077-2088, 2013

42 Singer M, "Mitochondrial function in sepsis: acute phase versus multiple organ failure" 35 (35): S441-S448, 2007

43 Haden DW, "Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis" 176 : 768-777, 2007

44 McBride HM, "Mitochondria: more than just a powerhouse" 16 : R551-R560, 2006

45 Galluzzi L, "Mitochondria: master regulators of danger signalling" 13 : 780-788, 2012

46 Chan DC, "Mitochondria: dynamic organelles in disease, aging, and development" 125 : 1241-1252, 2006

47 Jiang S, "Mitochondria and AMP-activated protein kinase-dependent mechanism of efferocytosis" 288 : 26013-26026, 2013

48 Levraut J, "Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction" 157 : 1021-1026, 1998

49 Kim J, "Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction" 289 : 23246-23255, 2014

50 Mickiewicz B, "Metabolomics as a novel approach for early diagnosis of pediatric septic shock and its mortality" 187 : 967-976, 2013

51 Rogers AJ, "Metabolomic derangements are associated with mortality in critically ill adult patients" 9 : e87538-, 2014

52 Englert JA, "Metabolism, metabolomics, and nutritional support of patients with sepsis" 37 : 321-331, 2016

53 O'Neill LA, "Metabolism of inflammation limited by AMPK and pseudo-starvation" 493 : 346-355, 2013

54 Newsholme P, "Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages" 239 : 121-125, 1986

55 Ganeshan K, "Metabolic regulation of immune responses" 32 : 609-634, 2014

56 MacIver NJ, "Metabolic regulation of T lymphocytes" 31 : 259-283, 2013

57 Pearce EL, "Metabolic pathways in immune cell activation and quiescence" 38 : 633-643, 2013

58 Träger K, "Metabolic alterations in sepsis and vasoactive drug-related metabolic effects" 9 : 271-278, 2003

59 Takasu O, "Mechanisms of cardiac and renal dysfunction in patients dying of sepsis" 187 : 509-517, 2013

60 Sun Q, "Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth" 108 : 4129-4134, 211

61 Delano MJ, "Magic bullets and surrogate biomarkers circa 2009" 37 : 1796-1798, 2009

62 Wynn TA, "Macrophages in tissue repair, regeneration, and fibrosis" 44 : 450-462, 2016

63 Puskarich MA, "Lactate clearance in septic shock is not a surrogate for improved microcirculatory flow" 23 : 690-693, 2016

64 Fink MP, "Laboratory models of sepsis and septic shock" 49 : 186-196, 1990

65 Shelley O, "Interaction between the innate and adaptive immune systems is required to survive sepsis and control inflammation after injury" 20 : 123-129, 2003

66 Medzhitov R, "Innate immunity" 343 : 338-344, 2000

67 Calvano SE, "Inflamm and Host Response to Injury Large Scale Collab. Res. Program. A network- based analysis of systemic inflammation in humans" 437 : 1032-1037, 2005

68 Boulos M, "Impaired mitochondrial function induced by serum from septic shock patients is attenuated by inhibition of nitric oxide synthase and poly(ADP-ribose) synthase" 31 : 353-358, 2003

69 Park J, "Impact of metformin use on lactate kinetics in patients with evere sepsis and septic shock" 2016

70 Leentjens J, "Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change?" 187 : 1287-1293, 2013

71 Boomer JS, "Immunosuppression in patients who die of sepsis and multiple organ failure" 306 : 2594-2605, 2011

72 Loftus RM, "Immunometabolism: cellular metabolism turns immune regulator" 291 : 1-10, 2016

73 O'Neill LA, "Immunometabolism governs dendritic cell and macrophage function" 213 : 15-23, 2016

74 Wofford JA, "IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival" 111 : 2101-2111, 2008

75 Rathmell JC, "IL-7 enhances the survival and maintains the size of naive T cells" 167 : 6869-6876, 2001

76 Lu H, "Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis" 277 : 23111-23115, 2002

77 Duffield JS, "Host responses in tissue repair and fibrosis" 8 : 241-276, 2013

78 Levy E, "Hepatic changes produced by a single dose of endotoxin in the mouse" 52 : 477-502, 1968

79 Rittirsch D, "Harmful molecular mechanisms in sepsis" 8 : 776-787, 2008

80 Grégoire M, "HMGB1 induces neutrophil dysfunction in experimental sepsis and in patients who survive septic shock" 2016

81 Shi LZ, "HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells" 208 : 1367-1376, 2011

82 Cramer T, "HIF-1alpha is essential for myeloid cell-mediated inflammation" 112 : 645-657, 2003

83 Peyssonnaux C, "HIF-1alpha expression regulates the bactericidal capacity of phagocytes" 115 : 1806-1815, 2005

84 Carr EL, "Glutamine uptake and metabolism are coordinately regulated by ERK/ MAPK during T lymphocyte activation" 185 : 1037-1044, 2010

85 Park DW, "GSK3 β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury" 307 : L735-L745, 2014

86 Bone NB, "Frontline science: D1 dopaminergic receptor signaling activates the AMPK-bioenergetic pathway in macrophages and alveolar epithelial cells and reduces endotoxin-induced ALI" 101 : 357-365, 2017

87 Varis E, "FINNAKI study group. Evolution of blood lactate and 90-day mortality in septic shock. A post hoc analysis of the Finnaki study" 2016

88 Zmijewski JW, "Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase" 285 : 33154-33164, 2010

89 Angus DC, "Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care" 29 : 1303-1310, 2001

90 Mayr FB, "Epidemiology of severe sepsis" 5 : 4-11, 2014

91 박대원, "Epidemiological and Clinical Characteristics of Community- Acquired Severe Sepsis and Septic Shock: A Prospective Observational Study in 12 University Hospitals in Korea" 대한의학회 27 (27): 1308-1314, 2012

92 Pearce EL, "Enhancing CD8 T-cell memory by modulating fatty acid metabolism" 460 : 103-107, 2009

93 Borregaard N, "Energy metabolism of human neutrophils during phagocytosis" 70 : 550-557, 1982

94 O'Reilly M, "Endotoxin, sepsis, and the primrose path" 12 : 411-420, 1999

95 Mannam P, "Endothelial MKK3 is a critical mediator of lethal murine endotoxemia and acute lung injury" 190 : 1264-1275, 2013

96 Opal SM, "Effect of eritoran, an antagonist of MD2- TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial" 309 : 1154-1162, 2013

97 Geissmann F, "Development of monocytes, macrophages, and dendritic cells" 327 : 656-661, 2010

98 Faist E, "Depression of cellular immunity after major injury. Its association with posttraumatic complications and its reversal with immunomodulation" 121 : 1000-1005, 1986

99 Bone RC, "Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis" The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine 101 : 1644-1655, 1992

100 Pelekanou A, "Decrease of CD4-lymphocytes and apoptosis of CD14-monocytes are characteristic alterations in sepsis caused by ventilator-associated pneumonia: results from an observational study" 13 : R172-, 2009

101 Michalek RD, "Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets" 186 : 3299-3303, 2011

102 Everts B, "Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells" 120 : 1422-1431, 2012

103 Arts RJ, "Cellular metabolism of myeloid cells in sepsis" 101 : 151-164, 2017

104 Osellame LD, "Cellular and molecular mechanisms of mitochondrial function" 26 : 711-723, 2012

105 van der Windt GJ, "CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability" 110 : 14336-14341, 2013

106 Cheng SC, "Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis" 17 : 406-413, 2016

107 Jansen TC, "Blood lactate monitoring in critically ill patients: a systematic health technology assessment" 37 : 2827-2839, 2009

108 Gaieski DF, "Benchmarking the incidence and mortality of severe sepsis in the United States" 41 : 1167-1174, 2013

109 Fink MP, "Bench-to-bedside review: cytopathic hypoxia" 6 : 491-499, 2002

110 Brealey D, "Association between mitochondrial dysfunction and severity and outcome of septic shock" 360 : 219-223, 2002

111 Hotchkiss RS, "Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction" 27 : 1230-1251, 1999

112 Zmijewski JW, "Antiinflammatory effects of hydrogen peroxide in neutrophil activation and acute lung injury" 179 : 694-704, 2009

113 Deitch EA, "Animal models of sepsis and shock: a review and lessons learned" 9 : 1-11, 1998

114 Langley RJ, "An integrated clinico-metabolomic model improves prediction of death in sepsis" 5 : 195-195, 2013

115 Escobar DA, "Adenosine monophosphate-activated protein kinase activation protects against sepsis-induced organ injury and inflammation" 194 : 262-272, 2015

116 Sag D, "Adenosine 5'-monophosphate- activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype" 181 : 8633-8641, 2008

117 Barata JT, "Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells" 200 : 659-669, 2004

118 Park DW, "Activation of AMPK enhances neutrophil chemotaxis and bacterial killing" 19 : 387-398, 2013

119 Zhao X, "Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury" 295 : L497-L504, 2008

120 Lokhandwala S, "Absolute lactate value vs relative reduction as a predictor of mortality in severe sepsis and septic shock" 37 : 179-184, 2017

121 Mounier R, "AMPK α1 regulates macrophage skewing at the time of resolution of inflammation during skeletal muscle regeneration" 18 : 251-264, 2013

122 Bae HB, "AMP-activated protein kinase enhances the phagocytic ability of macrophages and neutrophils" 25 : 4358-4368, 2011

123 Liu Z, "AMP-activated protein kinase and Glycogen Synthase Kinase 3β modulate the severity of sepsis-induced lung injury" 2015