Share / Export Citation / Email / Print / Text size:

Postępy Mikrobiologii - Advancements of Microbiology

Polish Society of Microbiologists

Subject: Microbiology


ISSN: 0079-4252
eISSN: 2545-3149





Volume / Issue / page

Related articles

VOLUME 57 , ISSUE 4 (April 2018) > List of articles


Agata Poniewierska-Baran / Beata Tokarz-Deptuła * / Wiesław Deptuła

Keywords : danger theory, danger factors, DAMP

Citation Information : Postępy Mikrobiologii - Advancements of Microbiology. Volume 57, Issue 4, Pages 328-337, DOI: https://doi.org/10.21307/PM-2018.57.4.328

License : (CC BY-NC-ND 4.0)

Published Online: 24-May-2019



The immune system of mammals has developed many mechanisms to effectively defend itself against foreign factors, including pathogens. In 1994, Polly Matzinger published a theory of danger, a new view in immunology, describing the response of the immune system to danger, caused by trauma and/or presence of pathogens. This theory sheds a different view on the current belief, that the immune system distinguishes between own (self) and foreign (non-self) structures and reacts only to non-self factors. According to the danger theory, the immune system has the ability to verify “safe” and “dangerous” factors, thus explaining immune reactions caused by tissue damage, referred to as “sterile inflammation”, but also occurring during the infection. It is believed that the fundamental elements in danger theory are dangerous molecules i.e. – damage-associated molecular patterns (DAMPs), which are released from damaged or dead tissue and cells. They are also present in physiological conditions and give analogous immune response to these induced by self/ non-self factors.

Content not available PDF Share



1. Abbas A.K., Lichtman A.H., Pober J.S.: Cellular and molecular immunology, wyd. 4., W.B. Saunders Company, Philadelphia, 2000

2. Abraham E.: Unraveling the role of high mobility group box protein 1 in severe trauma. Critical Care, 13, 1004 (2009)

3. Ahrens S., Schulz O. i wsp.: F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity, 36, 635–645 (2012)

4. Apetoh L., Zitvogel L. i wsp.: The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol. Rev. 220, 47–59 (2007)

5. Banjara M., Ghosh C.: Sterile Neuroinflammation and Strategies for Therapeutic Intervention. Int. J. Inflam. 2017, 8385961 (2017)

6. Bianchi M.E.: DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leuk. Biol. 81, 1–5 (2007)

7. Billingham R.E., Brent L., Medawar P.B.: Actively acquired tolerance of foreign cells. Nature, 172, 603–606 (1953)

8. Biragyn A., Kwak L.W. i wsp.: Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science, 298, 1025–1029 (2002)

9. Birger Y., Catez F., Furusawa T., Lim J.H., Prymakowska-Bosak M., West K.L., Postnikov Y.V., Haines D.C., Bustin M.: Increased tumorigenicity and sensitivity to ionizing radiation upon loss of chromosomal protein HMGN1. Cancer Res. 65, 6711–6718 (2005)

10. Bonawitz N.D., Clayton D.A., Shadel G.S.: Initiation and beyond: multiple functions of the human mitochondrial transcription machinery. Mol. Cell. 24, 813–825 (2006)

11. Bonilla W.V., Pinschewer D.D. i wsp.: The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses. Science, 335, 984–989 (2012)

12. Borges T.J., Lang B.J., Lopes R.L., Bonorino C.: Modulation of alloimmunity by heat shock proteins. Front. Immunol. 7, 303 (2016)

13. Burnet F.M.: Immunological recognition of self. Nobel Lecture, (1960)

14. Burnet F.M., Fenner F.: The production of antibodies, wyd. 2, Macmillan, Melbourne, 1949

15. Burnstock G., Fredholm B.B., North R.A., Verkhratsky A.: The birth and postnatal development of purinergic signalling. Acta Physiol. 199, 93–147 (2010)

16. Busso N., So A.: Mechanisms of inflammation in gout. Arthritis Res. Ther. 12, 206 (2010)

17. Calderwood S.K., Stevenson M.A., Murshid A.: Heat shock proteins, autoimmunity and cancer treatment. Autoimmune Dis. 2012, 486069 (2012)

18. Carp H.: Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils. J. Exp. Med. 155, 264–275 (1982)

19. Chotjumlong P., Bolscher J.G., Nazmi K., Reutrakul V., Supanchart C., Buranaphatthana W., Krisanaprakornkit S.: Involvement of the P2X7 purinergic receptor and c-Jun N-terminal and extracellular signal-regulated kinases in cyclooxygenase-2 and prostaglandin E2 induction by LL-37. J. Innate Immun. 5, 72–83 (2013)

20. Cohen I., Rider P., Carmi Y., Braiman A., Dotan S., White M.R., Voronov E., Martin M.U., Dinarello C.A., Apte R.N.: Diffe-
rential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc. Natl. Acad. Sci. USA, 107, 2574–2579 (2010)

21. Cohen E.S., Mustelin T. i wsp.: Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation. Nat. Commun. 6, 8327 (2015)

22. Da Rocha A.B., Regner A. i wsp.: Serum Hsp70 as an early predictor of fatal outcome after severe traumatic brain injury in males. J. Neurotrauma, 22, 966–977 (2005)

23. Duprez L., Takahashi N., van Hauwermeiren F., Vandendriessche B., Goossens V.: RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity, 35, 908–918 (2011)

24. Działo J., Tokarz-Deptuła B., Deptuła W.: Excitotoxicity and Wallerian degeneration as a processes related to cell death in nervous system. Arch. Ital. Biol. 151, 67–75 (2013)

25. Eil R., Restifo N.P. i wsp.: Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature, 537, 539–543 (2016)

26. Ellerman J.E., Brown C.K., de Vera M., Zeh H.J., Billiar T., Rubartelli A., Lotze M.T.: Masquerader: high mobility group box-1 and cancer. Clin. Cancer Res. 13, 2836–2848 (2007)

27. Elliott M.R., Koster K.M., Murphy P.S.: Efferocytosis signaling in the regulation of macrophage inflammatory responses. J. Immunol. 198, 1387–1394 (2017)

28. Faist E., Wichmann M.W.: Immunology in the severely injured. Der Chirurg, 68, 1066–1070 (1997)

29. Fucikova J., Spisek R. i wsp.: Prognostic and predictive value of DAMPs and DAMP – associated processes in cancer. Front. Immunol. 6, 402 (2015)

30. Gallucci S., Lolkema M., Matzinger P.: Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 5, 1249–1255 (1999)

31. Galluzzi L., Kepp O., Kroemer G.: Mitochondria: master regulators of danger signalling. Nat. Rev. Mol. Cell Biol. 13, 780–788 (2012)

32. Ganguly D., Chamilos G., Lande R., Gregorio J., Meller S., Facchinetti V., Homey B., Barrat F.J., Zal T., Gilliet M.: Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J. Exp. Med. 206, 1983–1994 (2009)

33. Garg A.D., Agostinis P.: Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses. Immunol. Rev. 280, 126–148 (2017)

34. Garg A.D., Agostinis P. i wsp.: Molecular and translational classifications of DAMPs in immunogenic cell death. Front. Immunol. 6, 588 (2015)

35. Garg A.D., Agostinis P. i wsp.: A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 31, 1062–1079 (2012)

36. Ghavami S., Kerkhoff C., Los M., Hashemi M., Sorg C., Karami-Tehrani F.: Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions. J. Leukoc. Biol. 76, 169–175 (2004)

37. Goh F.G., Piccinini A.M., Krausgruber T., Udalova I.A., Midwood K.S.: Transcriptional regulation of the endogenous danger signal tenascin-C: a novel autocrine loop in inflammation. J. Immunol. 184, 2655–2662 (2010)

38. Grasset E.K., Duhlin A., Agardh H.E., Ovchinnikova O., Hägglöf T., Forsell M.N., Paulsson-Berne G., Hansson G.K., Ketelhuth D.F., Karlsson M.C.: Sterile inflammation in the spleen during atherosclerosis provides oxidation-specific epitopes that induce a protective B-cell response. Proc. Natl. Acad. Sci. USA, 112, 2030–2038 (2015)

39. Hangai S., Ao T., Kimura Y., Matsuki K., Kawamura T., Negishi H., Nishio J., Kodama T., Taniguchi T., Yanai H.: PGE2 induced in and released by dying cells functions as an inhibitory DAMP. Proc. Natl. Acad. Sci. USA, 113, 3844–3849 (2016)

40. Harris H.E., Andersson U., Pisetsky D.S.: HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat. Rev. Rheumatol. 8, 195–202 (2012)

41. Hirsiger S., Simmen H.P., Werner C.M., Wanner G.A., Rittirsch D.: Danger signals activating the immune response after trauma. Mediators Inflamm. 2012, 315941 (2012)

42. Hodzic Z., Schill E.M., Bolock A.M., Good M.: IL-33 and the intestine: The good, the bad, and the inflammatory. Cytokine, 100, 1–10 (2017)

43. Hoque R., Farooq A., Mehal W.Z.: Sterile inflammation in the liver and pancreas. J. Gastroenterol. Hepatol. 28, 61–67 (2013)

44. Howell M.D., Gallo R.L., Boguniewicz M., Jones J.F., Wong C., Streib J.E., Leung D.Y.: Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity, 24, 341–348 (2006)

45. Huang H., Tsung A. i wsp.: Endogenous histones function as alarmins in sterile inflammatory liver injury through Toll-like receptor 9 in mice. Hepatology, 54, 999–1008 (2011)

46. Huynh M.L., Fadok V.A., Henson P.M.: Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J. Clin. Invest. 109, 41–50 (2002)

47. Iyer S.S., Sutterwala F.S. i wsp.: Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl. Acad. Sci. USA, 106, 20388 (2009)

48. Jouault T., El Abed-El Behi M., Martínez-Esparza M., Breuilh L., Trinel P.A., Chamaillard M., Trottein F., Poulain D.: Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling. J. Immunol. 177, 4679–4687 (2006)

49. Klune J.R., Dhupar R., Cardinal J., Billiar T.R., Tsung A.: HMGB1: endogenous danger signaling. Mol. Med. 14, 476–484 (2008)

50. Kono H., Rock K.L.: How dying cells alert the immune system to danger. Nat. Rev. Immunol. 8, 279 (2008)

51. Korbelik M., Banáth J., Sun J., Canals D., Hannun Y.A., Separovic D.: Ceramide and sphingosine-1-phosphate act as photodynamic therapy-elicited damage-associated molecular patterns: cell surface exposure. Int. Immunopharmacol. 20, 359–365 (2014)

52. Krispin A., Bledi Y., Atallah M., Trahtemberg U., Verbovetski I., Nahari E., Zelig O., Linial M., Mevorach D.: Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states. Blood, 108, 3580–3589 (2006)

53. Krysko D.V., Garg A.D., Kaczmarek A., Krysko O., Agostinis P., Vandenabeele P.: Immunogenic cell death and DAMPs in cancer therapy. Nat. Rev. Cancer. 12, 860–875 (2012)

54. Kumar H., Bot A.: In this tissue: Innate immunity and infectious diseases-an update. Int. Rev. Immunol. 36, 55–56 (2017)

55. Kumar H., Kawai T., Akira S.: Pathogen recognition by the innate immune system. Int. Rev. Immunol. 30, 16–34 (2011)

56. Kumar J., Okada S., Clayberger C., Krensky A.M.: Granulysin: a novel antimicrobial. Expert Opin Investig Drugs, 10, 321–329 (2001)

57. Lam N.Y., Rainer T.H., Chiu R.W., Joynt G.M., Lo Y.M.: Plasma mitochondrial DNA concentrations after trauma. Clin. Chem. 50, 213–216 (2004)

58. Lauber K., Wesselborg S. i wsp.: Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell, 113, 717–730 (2003)

59. Lenz A., Franklin G.A., Cheadle W.G.: Systemic inflammation after trauma. Injury, 38, 1336–1345 (2007)

60. Liu Z.X., Han D., Gunawan B., Kaplowitz N.: Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology, 43, 1220 (2006)

61. Majno G., Joris I.: Apoptosis, oncosis, and necrosis. An overview of cell death. Am. J. Pathol. 146, 3–15 (1995)

62. Martin N.T., Martin M.U.: Interleukin 33 is a guardian of barriers and a local alarmin Nat. Immunol. 17, 122–131 (2016)

63. Matzinger P.: Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12, 991–1045 (1994)

64. Matzinger P.: An innate sense of danger. Semin. Immunol. 10, 399–415 (1998)

65. Matzinger P.: The danger model: a renewed sense of self. Science, 296, 301–305 (2002)

66. McDonald B., Pittman K., Menezes G.B., Hirota S.A., Slaba I., Waterhouse C.C., Beck P.L., Muruve D.A., Kubes P.: Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science, 330, 362–366 (2010)

67. Meisner M., Tschaikowsky K., Hutzler A., Schick C., Schüttler J.: Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med. 24, 680–684 (1998)

68. Michaud M., Kroemer G. i wsp.: Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science, 334, 1573–1577 (2011)

69. Muller S., Scaffidi P., Degryse B., Bonaldi T., Ronfani L.: New EMBO members’ review: the double life of HMGB1 chromatin protein: architectural factor and extracellular signal. EMBO J. 20, 4337–4340 (2001)

70. Niedźwiedzka-Rystwej P., Deptuła W.: Defensins: An important innate element of the immune system in mammals. Post. Hig. Med. Dosw. 62, 524–529 (2008)

71. Niyonsaba F., Someya A., Hirata M., Ogawa H., Nagaoka I.: Evaluation of the efects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Eur. J. Immunol. 31, 1066–1075 (2001)

72. Nishiya T., DeFranco A.L.: Ligand-regulated chimeric receptor approach reveals distinctive subcellular localization and signaling properties of the Toll-like receptors. J. Biol. Chem. 279, 19008–19017 (2004)

73. Obeid M., Kroemer G. i wsp.: Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat. Med. 13, 54–61 (2007)

74. Oka T., Otsu K. i wsp.: Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature, 485, 251–255 (2012)

75. Osterloh A., Breloer M.: Heat shock proteins: linking danger and pathogen recognition. Med. Microbiol. Immunol. 197, 1–8 (2008)

76. Page R.C., Engel L.D., Narayanan A.S., Clagett J.A.: Chronic inflammatory gingival and periodontal disease. JAMA, 240, 545–550 (1978)

77. Pletjushkina O.Y., Skulachev V.P. i wsp.: Long-distance apoptotic killing of cells is mediated by hydrogen peroxide in a mitochondrial ROS-dependent fashion. Cell Death Differ. 12, 1442–1444 (2005)

78. Ptak W., Ptak M., Płytycz B.: Co rozpoznaje układ immunologiczny? Na drodze do nowego paradygmatu. Kosmos, 2–3, 149–156 (2003)

79. Pullerits R., Bokarewa M., Jonsson I.M., Verdrengh M., Tarkowski A.: Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis. Rheumatology, 44, 32–39 (2005)

80. Power C., Fanning N., Redmond H.P.: Cellular apoptosis and organ injury in sepsis: a review. Shock, 18, 197–211 (2002)

81. Prohászka Z., Singh M., Nagy K., Kiss E., Lakos G., Duba J., Füst G.: Heat shock protein 70 is a potent activator of the human complement system. Cell Stress Chaperones, 7, 17–22 (2002)

82. Raoof M., Zhang Q., Itagaki K., Hauser C.J.: Mitochondrial peptides are potent immune activators that activate human neutrophils via FPR-1. J. Trauma, 68, 1328–1332 (2010)

83. Raucci A., Palumbo R., Bianchi M.E.: HMGB1: a signal of necrosis. Autoimmunity, 40, 285–289 (2007)

84. Ren B., Zou G., Huang Y., Xu G., Xu F., He J., Zhu H., Yu P.: Serum levels of HSP70 and other DAMP proteins can aid in patient diagnosis after traumatic injury. Cell Stress Chaperones, 21, 677–686 (2016)

85. Riddell J.R., Wang X.Y., Minderman H., Gollnick S.O.: Peroxiredoxin 1 stimulates secretion of proinflammatory cytokines by binding to TLR4. J. Immunol. 184, 1022–1030 (2010)

86. Rittirsch D., Ward P.A. i wsp.: Functional roles for C5a receptors in sepsis. Nat. Med. 14, 551–557 (2008)

87. Rondas D., Mathieu C. i wsp.: Citrullinated glucose-regulated protein 78 is an autoantigen in type 1 diabetes. Diabetes, 64, 573–586 (2015)

88. Rovlias A., Kotsou S.: The blood leukocyte count and its prognostic significance in severe head injury. Surg. Neurol. 55, 190–196 (2001)

89. Schaefer L.: Extracellular matrix molecules: endogenous danger signals as new drug targets in kidney diseases. Curr. Opin. Pharmacol. 10, 185–190 (2010)

90. Segal A.W.: How neutrophils kill microbes. Annu. Rev. Immunol. 23, 197–223 (2005)

91. Sha Y., Zmijewski J., Xu Z., Abraham E.: HMGB1 develops enhanced proinflammatory activity by binding to cytokines.
J. Immunol. 180, 2531–2537 (2008)

92. Shi Y., Evans J.E., Rock K.L.: Molecular identification of a danger signal that alerts the immune system to dying cells. Nature, 425, 516–521 (2003)

93. Sorice M., Circella A., Cristea I.M., Garofalo T., Di Renzo L., Alessandri C., Valesini G., Esposti M.D.: Cardiolipin and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis. Cell Death Differ. 11, 1133–1145 (2004)

94. Tesniere A., Apetoh L., Ghiringhelli F., Joza N., Panaretakis T., Kepp O., Schlemmer F., Zitvogel L., Kroemer G.: Immunogeniccancer cell death: a key-lock paradigm. Curr. Opin. Immunol. 20, 504–511 (2008)

95. Tesniere A., Panaretakis T., Kepp O., Apetoh L., Ghiringhelli F., Zitvogel L., Kroemer G.: Molecular characteristics of immunogenic cancer cell death. Cell Death Differ. 15, 3–12 (2008)

96. Tschopp J., Schroder K.: NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nat. Rev. Immunol. 10, 210 (2010)

97. Tsung A., Sahai R., Tanaka H., Nakao A., Fink M.P., Lotze M.T., Yang H., Li J., Tracey K.J., Geller D.A., Billiar T.R.: The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J. Exp. Med. 201, 1135–1143 (2005)

98. Walko T.D. III, Bola R.A., Hong J.D., Au A.K., Bell M.J., Kochanek P.M., Clark R.S., Aneja R.K.: Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury. Shock, 41, 499–503 (2014)

99. Wallin I.E.: A note on the morphology of bacteria symbiotic in the tissues of higher organisms. J. Bacteriol. 7, 471–474 (1922)

100. Wallin R.P., Lundqvist A., Moré S.H., von Bonin A., Kiessling R., Ljunggren H.G.: Heat-shock proteins as activators of the innate immune system. Trends Immunol. 23, 130–135 (2002)

101. Wang H., Tracey K.J. i wsp.: HMG-1 as a late mediator of endotoxin lethality in mice. Science, 285, 248–251 (1999)

102. Wang H., Yang H., Tracey K.J.: Extracellular role of HMGB1 in inflammation and sepsis. J. Intern. Med. 255, 320–331 (2004)

103. Wei F., Yang D., Tewary P., Li Y., Li S., Chen X., Howard O.M., Bustin M., Oppenheim J.J.: The alarmin HMGN1 contributes to antitumor immunity and is a potent immunoadjuvant. Can. Res. 74, 5989–5998 (2014)

104. West A.P., Koblansky A.A., Ghosh S.: Recognition and signaling by toll-like receptors. Annu. Rev. Cell Dev. Biol. 22, 409–437 (2006)

105. Weyd H., Abeler-Dörner L., Linke B., Mahr A., Jahndel V., Pfrang S., Schnölzer M., Falk C.S., Krammer P.H.: Annexin A1 on the surface of early apoptotic cells suppresses CD8+ T cell immunity. Plos One, 8, e62449 (2013)

106. Vacchelli E., Kroemer G. i wsp.: Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1. Science, 350, 972–978 (2015)

107. Vance R.E.: A Copernican revolution? Doubts about the danger theory. J. Immunol. 165, 1725–1728 (2010)

108. Vandenabeele P., Galluzzi L., Vanden Berghe T., Kroemer G.: Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat. Rev. Mol. Cell Biol. 11, 700–714 (2010)

109. Yang D., Han Z., Oppenheim J.J.: Alarmins and immunity. Immunol. Rev. 280, 41–56 (2017)

110. Yang D., Oppenheim J.J. i wsp.: High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses. J. Exp. Med. 209, 157–171 (2012)

111. Yang D., Biragyn A., Hoover D.M., Lubkowski J., Oppenheim J.J.: Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu. Rev. Immunol. 22, 181–315 (2004)

112. Yang D., Bustin M., Oppenheim J.J.: Harnessing the alarmin HMGN1 for anticancer therapy. Immunotherapy, 7, 1129–1131 (2015)

113. Yang D., Chen Q,. Schmidt A.P., Anderson G.M., Wang J.M., Wooters J., Oppenheim J.J., Chertov O.: LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J. Exp. Med. 192, 1069–1074 (2000)

114. Yao Y.M., Redl H., Bahrami S., Schlag G.: The inflammatory basis of trauma/shock-associated multiple organ failure. Inflamm. Res. 47, 201–210 (1998)

115. Yendamuri S., Fulda G.J., Tinkoff G.H.: Admission hyperglycemia as a prognostic indicator in trauma. J. Trauma, 55, 33–38 (2003)

116. Yoon K.W., Lee S.W. i wsp.: Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science, 349, 1261669 (2015)

117. Zhang Q., Itagaki K., Hauser C.J.: Mitochondrial DNA is released by shock and activates neutrophils via P38 map kinase. Shock, 34, 55–59 (2010)

118. Zhou J., Hodi F.S. i wsp.: Soluble PD- L1 as a biomarker in malignant melanoma and checkpoint blockade. Cancer Immunol. Res. 5, 480–492 (2017)

119. Zhou R., Tardivel A., Thorens B., Choi I., Tschopp J.: Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 11, 136–140 (2010)