Endogenous DAMPs, Category III: Inducible DAMPs (Cat. III DAMPs)

  • Walter Gottlieb Land


In this chapter, evidence from the international literature is collected demonstrating that inducible DAMPs as an own category in the classification, besides DAMPs passively released from necrotic cells, are an integral part of the innate immune system evolved to react in a tailor-made fashion with inflammation-promoting and inflammation-resolving responses. In accordance with their different emission and function, the inducible DAMPs are divided into three classes described in single subchapters entitled (1) native molecules operating as inducible DAMPs, (2) modified molecules acting as inducible DAMPs, and (3) suppressing DAMPs, denoted as inducible “SAMPs.” The most prominent subclasses of native molecules include the cytokines tumor necrosis factor and type I interferons that are actively secreted by DAMP-activated innate immune cells, vascular molecules released from Weibel–Palade bodies, and galectins. Prominent candidates of modified molecules include actively secreted, processed interleukin-1 family members, processed high mobility group box 1, and anaphylatoxins. Subgroups of SAMPs refer to molecules known to contribute not to promotion but to resolution of inflammation. They include prostaglandin E2, cyclic adenosine monophosphate, annexin A1, as well as distinct specialized pro-resolving lipid mediators. Together, the accumulating evidence qualifying inducible DAMPs as molecules involved in inflammation-promoting and inflammation-resolving responses is intriguing in that these functions demonstrate productive activity of the defense system even in scenarios of mild or moderate injury not characterized by the occurrence of cell death. However, in situations in which the damage is severe, secreted inducible DAMPs even cooperate in a tailor-made fashion with DAMPs passively released from necrotic cells, the total outcome being the orchestration of a robust host defense to life-threatening injuries such as caused by viral infections.


  1. 1.
    Rider P, Voronov E, Dinarello CA, Apte RN, Cohen I. Alarmins: feel the stress. J Immunol. 2017;198CrossRefPubMedGoogle Scholar
  2. 2.
    Martin SJ. Cell death and inflammation: the case for IL-1 family cytokines as the canonical DAMPs of the immune system. FEBS J. 2016;283:2599–615. Available from: CrossRefPubMedGoogle Scholar
  3. 3.
    Yatim N, Cullen S, Albert ML. Dying cells actively regulate adaptive immune responses. Nat Rev Immunol. 2017;17:262–75. Available from: CrossRefPubMedGoogle Scholar
  4. 4.
    Daniels M, Brough D. Unconventional pathways of secretion contribute to inflammation. Int J Mol Sci. 2017;18:102. Available from: CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Bromberg Z, Goloubinoff P, Saidi Y, Weiss YG. The membrane-associated transient receptor potential vanilloid channel is the central heat shock receptor controlling the cellular heat shock response in epithelial cells. PLoS One. 2013;e57149:8. Available from: Google Scholar
  6. 6.
    Kim Guisbert KS, Guisbert E. SF3B1 is a stress-sensitive splicing factor that regulates both HSF1 concentration and activity. PLoS One. 2017;12:e0176382. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    McMillan DR, Xiao X, Shao L, Graves K, Benjamin IJ. Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem. 1998;273:7523–8. Available from: CrossRefPubMedGoogle Scholar
  8. 8.
    Akerfelt M, Morimoto RI, Sistonen L. Heat shock factors: integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol. 2010;11:545–55. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mambula SS, Calderwood SK. Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes. J Immunol. 2006;177:7849–57. Available from: CrossRefPubMedGoogle Scholar
  10. 10.
    Guzhova I, Kislyakova K, Moskaliova O, Fridlanskaya I, Tytell M, Cheetham M, et al. In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res. 2001;914:66–73. Available from: CrossRefPubMedGoogle Scholar
  11. 11.
    Radons J, Multhoff G. Immunostimulatory functions of membrane-bound and exported heat shock protein 70. Exerc Immunol Rev. 2005;11:17–33. Available from: PubMedGoogle Scholar
  12. 12.
    Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, et al. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 2005;65:5238–47. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z. Induction of heat shock proteins in B-cell exosomes. J Cell Sci. 2005;118:3631–8. Available from: CrossRefPubMedGoogle Scholar
  14. 14.
    Lancaster GI, Febbraio MA. Exosome-dependent trafficking of HSP70. J Biol Chem. 2005;280:23349–55. Available from: CrossRefPubMedGoogle Scholar
  15. 15.
    Zhan R, Leng X, Liu X, Wang X, Gong J, Yan L, et al. Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes. Biochem Biophys Res Commun. 2009;387:229–33. Available from: CrossRefPubMedGoogle Scholar
  16. 16.
    Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin J-P, et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest. 2010;120:457–71. Available from: PubMedPubMedCentralGoogle Scholar
  17. 17.
    Takeuchi T, Suzuki M, Fujikake N, Popiel HA, Kikuchi H, Futaki S, et al. Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level. Proc Natl Acad Sci U S A. 2015;112:E2497–506. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Batulan Z, Pulakazhi Venu VK, Li Y, Koumbadinga G, Alvarez-Olmedo DG, Shi C, et al. Extracellular release and signaling by heat shock protein 27: role in modifying vascular inflammation. Front Immunol. 2016;7:285. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Santos TG, Martins V, Hajj G. Unconventional secretion of heat shock proteins in cancer. Int J Mol Sci. 2017;18:946. Available from: CrossRefPubMedCentralGoogle Scholar
  20. 20.
    De Toro J, Herschlik L, Waldner C, Mongini C. Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front Immunol. 2015;6:203. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T, et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 2012;31:1062–79. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol. 2015;6:588. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Burnstock G, Knight GE. Cell culture: complications due to mechanical release of ATP and activation of purinoceptors. Cell Tissue Res. 2017;370:1–11. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Bloy N, Garcia P, Laumont CM, Pitt JM, Sistigu A, Stoll G, et al. Immunogenic stress and death of cancer cells: contribution of antigenicity vs adjuvanticity to immunosurveillance. Immunol Rev. 2017;280:165–74. Available from: CrossRefPubMedGoogle Scholar
  25. 25.
    Junger WG. Immune cell regulation by autocrine purinergic signalling. Nat Rev Immunol. 2011;11:201–12. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H. Purinergic signalling in the nervous system: an overview. Trends Neurosci. 2009;32:19–29. Available from: CrossRefPubMedGoogle Scholar
  27. 27.
    Moriyama Y, Hiasa M, Sakamoto S, Omote H, Nomura M. Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling. Purinergic Signal. 2017;13:387–404. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Xia J, Lim JC, Lu W, Beckel JM, Macarak EJ, Laties AM, et al. Neurons respond directly to mechanical deformation with pannexin-mediated ATP release and autostimulation of P2X 7 receptors. J Physiol. 2012;590:2285–304. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Begandt D, Good ME, Keller AS, DeLalio LJ, Rowley C, Isakson BE, et al. Pannexin channel and connexin hemichannel expression in vascular function and inflammation. BMC Cell Biol. 2017;18:2. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Whyte-Fagundes P, Zoidl G. Mechanisms of pannexin1 channel gating and regulation. Biochim Biophys Acta. 2017;1860(1):65–71. Available from: CrossRefGoogle Scholar
  31. 31.
    Sohl G, Willecke K. Gap junctions and the connexin protein family. Cardiovasc Res. 2004;62:228–32. Available from: CrossRefPubMedGoogle Scholar
  32. 32.
    Chiu Y-H, Jin X, Medina CB, Leonhardt SA, Kiessling V, Bennett BC, et al. A quantized mechanism for activation of pannexin channels. Nat Commun. 2017;8:14324. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Qu Y, Misaghi S, Newton K, Gilmour LL, Louie S, Cupp JE, et al. Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol. 2011;186:6553–61. Available from: CrossRefPubMedGoogle Scholar
  34. 34.
    Ayna G, Krysko DV, Kaczmarek A, Petrovski G, Vandenabeele P, Fésüs L. ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages. PLoS One. 2012;7:e40069. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Robertson J, Lang S, Lambert PA, Martin PE. Peptidoglycan derived from Staphylococcus epidermidis induces Connexin43 hemichannel activity with consequences on the innate immune response in endothelial cells. Biochem J. 2010;432:133–43. Available from: CrossRefPubMedGoogle Scholar
  36. 36.
    Garg AD, Agostinis P. ER stress, autophagy and immunogenic cell death in photodynamic therapy-induced anti-cancer immune responses. Photochem Photobiol Sci. 2014;13:474–87. Available from: CrossRefPubMedGoogle Scholar
  37. 37.
    Martin S, Dudek-Peric AM, Garg AD, Roose H, Demirsoy S, Van Eygen S, et al. An autophagy-driven pathway of ATP secretion supports the aggressive phenotype of BRAF V600E inhibitor-resistant metastatic melanoma cells. Autophagy. 2017:1–16. Available from:
  38. 38.
    Frosch M, Strey A, Vogl T, Wulffraat NM, Kuis W, Sunderkötter C, et al. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum. 2000;43:628–37. Available from: CrossRefPubMedGoogle Scholar
  39. 39.
    Rammes A, Roth J, Goebeler M, Klempt M, Hartmann M, Sorg C. Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. J Biol Chem. 1997;272:9496–502. Available from: CrossRefPubMedGoogle Scholar
  40. 40.
    Tardif MR, Chapeton-Montes JA, Posvandzic A, Pagé N, Gilbert C, Tessier PA. Secretion of S100A8, S100A9, and S100A12 by neutrophils involves reactive oxygen species and potassium efflux. J Immunol Res. 2015;2015:1–16. Available from: CrossRefGoogle Scholar
  41. 41.
    Murray RZ, Stow JL. Cytokine secretion in macrophages: SNAREs, rabs, and membrane trafficking. Front Immunol. 2014;5:538. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Adrain C, Zettl M, Christova Y, Taylor N, Freeman M. Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science. 2012;335:225–8. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, et al. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science. 2012;335:229–32. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Aggarwal BB, Gupta SC, Kim JH. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 2012;119:651–65. Available from: Scholar
  45. 45.
    Sedger LM, McDermott MF. TNF and TNF-receptors: from mediators of cell death and inflammation to therapeutic giants – past, present and future. Cytokine Growth Factor Rev. 2014;25:453–72. Available from: CrossRefPubMedGoogle Scholar
  46. 46.
    Brenner D, Blaser H, Mak TW. Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol. 2015;15:362–74. Available from: CrossRefPubMedGoogle Scholar
  47. 47.
    Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. 2016;12:49–62. Available from: CrossRefPubMedGoogle Scholar
  48. 48.
    Blaser H, Dostert C, Mak TW, Brenner D. TNF and ROS crosstalk in Inflammation. Trends Cell Biol. 2016;26:249–61. Available from: CrossRefPubMedGoogle Scholar
  49. 49.
    Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, et al. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med. 2014;20:1301–9. Available from: CrossRefPubMedGoogle Scholar
  50. 50.
    Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol. 2015;15:405–14. Available from: CrossRefPubMedGoogle Scholar
  51. 51.
    Shen X-D, Ke B, Ji H, Gao F, Freitas MCS, Chang WW, et al. Disruption of type-I IFN pathway ameliorates preservation damage in mouse orthotopic liver transplantation via HO-1 dependent mechanism. Am J Transplant. 2012;12:1730–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Trinchieri G. Type I interferon: friend or foe? J Exp Med. 2010;207:2053–63. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14:36–49. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I interferons in infectious disease. Nat Rev Immunol. 2015;15:87–103. Available from: CrossRefPubMedGoogle Scholar
  55. 55.
    Erramilli S, Mannam P, Manthous CA. Influenza SIRS with minimal pneumonitis. Front Med. 2016;3:37. Available from: CrossRefGoogle Scholar
  56. 56.
    Plant EP, Ilyushina NA, Sheikh F, Donnelly RP, Ye Z. Influenza virus NS1 protein mutations at position 171 impact innate interferon responses by respiratory epithelial cells. Virus Res. 2017;240:81–6. Available from: CrossRefPubMedGoogle Scholar
  57. 57.
    Snyder DT, Hedges JF, Jutila MA. Getting “Inside” type I IFNs: type I IFNs in intracellular bacterial infections. J Immunol Res. 2017;2017:1–17. Available from: CrossRefGoogle Scholar
  58. 58.
    Cohen I, Rider P, Vornov E, Tomas M, Tudor C, Wegner M, et al. Erratum: corrigendum: IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity. Sci Rep. 2016;6:19100. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Rickard JA, O’Donnell JA, Evans JM, Lalaoui N, Poh AR, Rogers T, et al. RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell. 2014;157:1175–88. Available from: CrossRefPubMedGoogle Scholar
  60. 60.
    Martin-Sanchez D, Ruiz-Andres O, Poveda J, Carrasco S, Cannata-Ortiz P, Sanchez-Niño MD, et al. Ferroptosis, but not necroptosis, is important in nephrotoxic folic acid-induced AKI. J Am Soc Nephrol. 2017;28:218–29. Available from: CrossRefPubMedGoogle Scholar
  61. 61.
    Dinarello CA. Interleukin-1 family [IL-1F1, F2]. Cytokine Handb. 2003;2003:643–68.CrossRefGoogle Scholar
  62. 62.
    Fettelschoss A, Kistowska M, LeibundGut-Landmann S, Beer H-D, Johansen P, Senti G, et al. Inflammasome activation and IL-1β target IL-1α for secretion as opposed to surface expression. Proc Natl Acad Sci U S A. 2011;108:18055–60. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Rider P, Kaplanov I, Romzova M, Bernardis L, Braiman A, Voronov E, et al. The transcription of the alarmin cytokine interleukin-1 alpha is controlled by hypoxia inducible factors 1 and 2 alpha in hypoxic cells. Front Immunol. 2012;3:290. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Rubartelli A, Cozzolino F, Talio M, Sitia R. A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence. EMBO J. 1990;9:1503–10. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Johnston LK, Bryce PJ. Understanding interleukin 33 and its roles in eosinophil development. Front Med. 2017;4:51. Available from: CrossRefGoogle Scholar
  66. 66.
    Balato A, Lembo S, Mattii M, Schiattarella M, Marino R, De Paulis A, et al. IL-33 is secreted by psoriatic keratinocytes and induces pro-inflammatory cytokines via keratinocyte and mast cell activation. Exp Dermatol. 2012;21:892–4. Available from: CrossRefPubMedGoogle Scholar
  67. 67.
    Chen H, Sun Y, Lai L, Wu H, Xiao Y, Ming B, et al. Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice. Neuroscience. 2015;308:157–68. Available from: CrossRefPubMedGoogle Scholar
  68. 68.
    Madouri F, Guillou N, Fauconnier L, Marchiol T, Rouxel N, Chenuet P, et al. Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation. J Mol Cell Biol. 2015;7:351–65. Available from: CrossRefPubMedGoogle Scholar
  69. 69.
    Lefrançais E, Roga S, Gautier V, Gonzalez-de-Peredo A, Monsarrat B, Girard J-P, et al. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc Natl Acad Sci U S A. 2012;109:1673–8. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Blatt AZ, Pathan S, Ferreira VP. Properdin: a tightly regulated critical inflammatory modulator. Immunol Rev. 2016;274:172–90. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Ferreira VP, Cortes C, Pangburn MK. Native polymeric forms of properdin selectively bind to targets and promote activation of the alternative pathway of complement. Immunobiology. 2010;215:932–40. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Xu W, Berger SP, Trouw LA, de Boer HC, Schlagwein N, Mutsaers C, et al. Properdin binds to late apoptotic and necrotic cells independently of C3b and regulates alternative pathway complement activation. J Immunol. 2008;180:7613–21. Available from: CrossRefPubMedGoogle Scholar
  73. 73.
    Kemper C, Mitchell LM, Zhang L, Hourcade DE. The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis. Proc Natl Acad Sci U S A. 2008;105:9023–8. Available from: CrossRefGoogle Scholar
  74. 74.
    Cortes C, Ohtola JA, Saggu G, Ferreira VP. Local release of properdin in the cellular microenvironment: role in pattern recognition and amplification of the alternative pathway of complement. Front Immunol. 2012;3:412. Available from: PubMedGoogle Scholar
  75. 75.
    Bongrazio M, Pries AR, Zakrzewicz A. The endothelium as physiological source of properdin: role of wall shear stress. Mol Immunol. 2003;39:669–75. Available from: CrossRefPubMedGoogle Scholar
  76. 76.
    Yasuda K, Vasko R, Hayek P, Ratliff B, Bicer H, Mares J, et al. Functional consequences of inhibiting exocytosis of Weibel-Palade bodies in acute renal ischemia. Am J Physiol Renal Physiol. 2012;302:F713–21. Available from: CrossRefPubMedGoogle Scholar
  77. 77.
    Zhu QM, Yamakuchi M, Lowenstein CJ, Lowenstein CJ. SNAP23 regulates endothelial exocytosis of von willebrand factor. PLoS One. 2015;e0118737:10. Available from: Google Scholar
  78. 78.
    Kuo M-C, Patschan D, Patschan S, Cohen-Gould L, Park H-C, Ni J, et al. Ischemia-induced exocytosis of Weibel-Palade bodies mobilizes stem cells. J Am Soc Nephrol. 2008;19:2321–30. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Mourik M, Eikenboom J. Lifecycle of Weibel-Palade bodies. Hamostaseologie. 2017;37:13–24. Available from: CrossRefPubMedGoogle Scholar
  80. 80.
    Kawecki C, Lenting PJ, Denis CV. von Willebrand factor and inflammation. J Thromb Haemost. 2017;15:1285–94. Available from: CrossRefPubMedGoogle Scholar
  81. 81.
    Michels A, Albánez S, Mewburn J, Nesbitt K, Gould TJ, Liaw PC, et al. Histones link inflammation and thrombosis through the induction of Weibel-Palade Body exocytosis. J Thromb Haemost. 2016.; Available from:
  82. 82.
    McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res. 2015;107:331–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, et al. Endothelin. Pharmacol Rev. 2016;68:357–418. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    McCormack JJ, Lopes da Silva M, Ferraro F, Patella F, Cutler DF. Weibel−Palade bodies at a glance. J Cell Sci. 2017;130:3611–7. Available from: CrossRefPubMedGoogle Scholar
  85. 85.
    Pendu R, Terraube V, Christophe OD, Gahmberg CG, de Groot PG, Lenting PJ, et al. P-selectin glycoprotein ligand 1 and beta2-integrins cooperate in the adhesion of leukocytes to von Willebrand factor. Blood. 2006;108:3746–52. Available from: CrossRefPubMedGoogle Scholar
  86. 86.
    Zunino B, Rubio-Patiño C, Villa E, Meynet O, Proics E, Cornille A, et al. Hyperthermic intraperitoneal chemotherapy leads to an anticancer immune response via exposure of cell surface heat shock protein 90. Oncogene. 2016;35:261–8. Available from: CrossRefPubMedGoogle Scholar
  87. 87.
    Frimat M, Tabarin F, Dimitrov JD, Poitou C, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, et al. Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome. Blood. 2013;122:282–92. Available from: CrossRefPubMedGoogle Scholar
  88. 88.
    Stow LR, Jacobs ME, Wingo CS, Cain BD. Endothelin-1 gene regulation. FASEB J. 2011;25:16–28. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Qin W, Mi S, Li C, Wang G, Zhang J, Wang H, et al. Low shear stress induced HMGB1 translocation and release via PECAM-1/PARP-1 pathway to induce inflammation response. PLoS One. 2015:10, e0120586. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Liu Y, Yan W, Tohme S, Chen M, Fu Y, Tian D, et al. Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll-like receptor 9. J Hepatol. 2015;63:114–21. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Scharfstein J, Schmitz V, Svensjö E, Granato A, Monteiro AC. Kininogens coordinate adaptive immunity through the proteolytic release of bradykinin, an endogenous danger signal driving dendritic cell maturation. Scand J Immunol. 2007;66:128–36. Available from: CrossRefPubMedGoogle Scholar
  92. 92.
    Monteiro AC, Scovino A, Raposo S, Gaze VM, Cruz C, Svensjo E, et al. Kinin Danger signals proteolytically released by gingipain induce fimbriae-specific IFN- and IL-17-producing T cells in mice infected intramucosally with porphyromonas gingivalis. J Immunol. 2009;183:3700–11. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Yoshino O, Yamada-Nomoto K, Kobayashi M, Andoh T, Hongo M, Ono Y, et al. Bradykinin system is involved in endometriosis-related pain through endothelin-1 production. Eur J Pain. 2017.; Available from:
  94. 94.
    Adlbrecht C, Wurm R, Humenberger M, Andreas M, Redwan B, Distelmaier K, et al. Peri-interventional endothelin-A receptor blockade improves long-term outcome in patients with ST-elevation acute myocardial infarction. Thromb Haemost. 2014;112:176–82. Available from: CrossRefPubMedGoogle Scholar
  95. 95.
    Packer M, McMurray JJV, Krum H, Kiowski W, Massie BM, Caspi A, et al. Long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. JACC Hear Fail. 2017;5:317–26. Available from: CrossRefGoogle Scholar
  96. 96.
    Kuntz M, Leiva-Juarez MM, Luthra S. Systematic review of randomized controlled trials of endothelin receptor antagonists for pulmonary arterial hypertension. Lung. 2016;194:723–32. Available from: CrossRefPubMedGoogle Scholar
  97. 97.
    Yuan W, Cheng G, Li B, Li Y, Lu S, Liu D, et al. Endothelin-receptor antagonist can reduce blood pressure in patients with hypertension: a meta-analysis. Blood Press. 2017;26:139–49. Available from: CrossRefPubMedGoogle Scholar
  98. 98.
    Devuyst O, Olinger E, Rampoldi L. Uromodulin: from physiology to rare and complex kidney disorders. Nat Rev Nephrol. 2017;13:525–44. Available from: CrossRefPubMedGoogle Scholar
  99. 99.
    Anders H-J, Schaefer L. Beyond tissue injury-damage-associated molecular patterns, toll-like receptors, and inflammasomes also drive regeneration and fibrosis. J Am Soc Nephrol. 2014;25:1387–400. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Säemann MD, Weichhart T, Zeyda M, Staffler G, Schunn M, Stuhlmeier KM, et al. Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4-dependent mechanism. J Clin Invest. 2005;115:468–75. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Darisipudi MN, Thomasova D, Mulay SR, Brech D, Noessner E, Liapis H, et al. Uromodulin triggers IL-1β-dependent innate immunity via the NLRP3 inflammasome. J Am Soc Nephrol. 2012;23:1783–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Sato S, St-Pierre C, Bhaumik P, Nieminen J. Galectins in innate immunity: dual functions of host soluble beta-galactoside-binding lectins as damage-associated molecular patterns (DAMPs) and as receptors for pathogen-associated molecular patterns (PAMPs). Immunol Rev. 2009;230:172–87. Available from: CrossRefPubMedGoogle Scholar
  103. 103.
    Vasta GR, Feng C, González-Montalbán N, Mancini J, Yang L, Abernathy K, et al. Functions of galectins as “self/non-self”-recognition and effector factors. Pathog Dis. 2017;75:PMID:28449072. Available from: CrossRefGoogle Scholar
  104. 104.
    Leffler H, Carlsson S, Hedlund M, Qian Y, Poirier F. Introduction to galectins. Glycoconj J. 2002;19:433–40. Available from: CrossRefPubMedGoogle Scholar
  105. 105.
    Liu F-T, Patterson RJ, Wang JL. Intracellular functions of galectins. Biochim Biophys Acta. 2002;1572:263–73. Available from: CrossRefPubMedGoogle Scholar
  106. 106.
    Yang R-Y, Rabinovich GA, Liu F-T. Galectins: structure, function and therapeutic potential. Expert Rev Mol Med. 2008;10:e17. Available from: CrossRefPubMedGoogle Scholar
  107. 107.
    Stewart SE, Menzies SA, Popa SJ, Savinykh N, Petrunkina Harrison A, Lehner PJ, et al. A genome-wide CRISPR screen reconciles the role of N-linked glycosylation in galectin-3 transport to the cell surface. J Cell Sci. 2017;130:3234–47. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Ouellet M, St-Pierre C, Tremblay MJ, Sato S. Effect of galectins on viral transmission. Methods Mol Biol. 2015;1207:397–420. Available from: CrossRefPubMedGoogle Scholar
  109. 109.
    Sato S, Ouellet M, St-Pierre C, Tremblay MJ. Glycans, galectins, and HIV-1 infection. Ann N Y Acad Sci. 2012;1253:133–48. Available from: CrossRefPubMedGoogle Scholar
  110. 110.
    Dapat I, Pascapurnama D, Iwasaki H, Labayo H, Chagan-Yasutan H, Egawa S, et al. Secretion of galectin-9 as a DAMP during dengue virus infection in THP-1 cells. Int J Mol Sci. 2017;18:1644. Available from: CrossRefPubMedCentralGoogle Scholar
  111. 111.
    Kim B, Lee Y, Kim E, Kwak A, Ryoo S, Bae SH, et al. The interleukin-1α precursor is biologically active and is likely a key alarmin in the IL-1 family of cytokines. Front Immunol. 2013;4:391. Available from: PubMedPubMedCentralGoogle Scholar
  112. 112.
    Alheim K, McDowell TL, Symons JA, Duff GW, Bartfai T. An AP-1 site is involved in the NGF induction of IL-1 alpha in PC12 cells. Neurochem Int. 1996;29:487–96. Available from: CrossRefPubMedGoogle Scholar
  113. 113.
    Mori N, Prager D. Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins. Blood. 1996;87:3410–7. Available from: PubMedGoogle Scholar
  114. 114.
    Koo J-H, Yoon H, Kim W-J, Lim S, Park H-J, Choi J-M. Cell membrane penetrating function of the nuclear localization sequence in human cytokine IL-1α. Mol Biol Rep. 2014;41:8117–26. Available from: CrossRefPubMedGoogle Scholar
  115. 115.
    Lange A, Mills RE, Lange CJ, Stewart M, Devine SE, Corbett AH. Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem. 2007;282:5101–5. Available from: CrossRefPubMedGoogle Scholar
  116. 116.
    Lange A, McLane LM, Mills RE, Devine SE, Corbett AH. Expanding the definition of the classical bipartite nuclear localization signal. Traffic. 2010;11:311–23. Available from: CrossRefPubMedGoogle Scholar
  117. 117.
    Kavita U, Mizel SB. Differential sensitivity of interleukin-1 alpha and -beta precursor proteins to cleavage by calpain, a calcium-dependent protease. J Biol Chem. 1995;270:27758–65. Available from: CrossRefPubMedGoogle Scholar
  118. 118.
    Zheng Y, Humphry M, Maguire JJ, Bennett MR, Clarke MCH. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1α, controlling necrosis-induced sterile inflammation. Immunity. 2013;38:285–95. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Kobayashi Y, Yamamoto K, Saido T, Kawasaki H, Oppenheim JJ, Matsushima K. Identification of calcium-activated neutral protease as a processing enzyme of human interleukin 1 alpha. Proc Natl Acad Sci U S A. 1990;87:5548–52. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Keller M, Rüegg A, Werner S, Beer H-D. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 2008;132:818–31. Available from: CrossRefPubMedGoogle Scholar
  121. 121.
    Afonina IS, Tynan GA, Logue SE, Cullen SP, Bots M, Lüthi AU, et al. Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α. Mol Cell. 2011;44:265–78. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity. 2013;38:209–23. Available from: CrossRefPubMedGoogle Scholar
  123. 123.
    England H, Summersgill HR, Edye ME, Rothwell NJ, Brough D. Release of interleukin-1α or interleukin-1β depends on mechanism of cell death. J Biol Chem. 2014;289:15942–50. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Wang L, Wang T, Li H, Liu Q, Zhang Z, Xie W, et al. Receptor interacting protein 3-mediated necroptosis promotes lipopolysaccharide-induced inflammation and acute respiratory distress syndrome in mice. PLoS One. 2016;11:e0155723. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Zhang L, Wei J, Ren L, Zhang J, Yang M, Jing L, et al. Endosulfan inducing apoptosis and necroptosis through activation RIPK signaling pathway in human umbilical vascular endothelial cells. Environ Sci Pollut Res. 2017;24:215–25. Available from: CrossRefGoogle Scholar
  126. 126.
    Alam J, Jantan I, Bukhari SNA. Rheumatoid arthritis: recent advances on its etiology, role of cytokines and pharmacotherapy. Biomed Pharmacother. 2017;92:615–33. Available from: CrossRefPubMedGoogle Scholar
  127. 127.
    Conos SA, Chen KW, De Nardo D, Hara H, Whitehead L, Núñez G, et al. Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner. Proc Natl Acad Sci. 2017;114:E961–9. Available from: CrossRefPubMedGoogle Scholar
  128. 128.
    Sarhan M, Land WG, Tonnus W, Hugo CP, Linkermann A. Origin and consequences of necroinflammation. Physiol Rev. 2018;98(2):727–80.CrossRefPubMedGoogle Scholar
  129. 129.
    Land WG. Innate alloimmunity part 2: innate immunity and allograft rejection. Baskent University, Ankara; Pabst Science Publishers, Lengerich. 2011. Available from: ISBN 978-3-89967-738-6.Google Scholar
  130. 130.
    Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, et al. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 2003;22:5551–60. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Lu B, Wang C, Wang M, Li W, Chen F, Tracey KJ, et al. Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review. Expert Rev Clin Immunol. 2014;10:713–27. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Lu B, Wang H, Andersson U, Tracey KJ. Regulation of HMGB1 release by inflammasomes. Protein Cell. 2013;4:163–7. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Tang Y, Zhao X, Antoine D, Xiao X, Wang H, Andersson U, et al. Regulation of posttranslational modifications of HMGB1 during immune responses. Antioxid Redox Signal. 2016;24:620–34. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Hao N, Budnik BA, Gunawardena J, O’Shea EK. Tunable signal processing through modular control of transcription factor translocation. Science. 2013;339:460–4. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Lu B, Antoine DJ, Kwan K, Lundbäck P, Wähämaa H, Schierbeck H, et al. JAK/STAT1 signaling promotes HMGB1 hyperacetylation and nuclear translocation. Proc Natl Acad Sci U S A. 2014;111:3068–73. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Andrei C, Margiocco P, Poggi A, Lotti LV, Torrisi MR, Rubartelli A. Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes. Proc Natl Acad Sci U S A. 2004;101:9745–50. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Griffiths GM. Secretion from myeloid cells: secretory lysosomes. Microbiol Spectr. 2016;4:PMID:27726815. Available from: Google Scholar
  138. 138.
    Marim FM, Franco MMC, Gomes MTR, Miraglia MC, Giambartolomei GH, Oliveira SC. The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection. Semin Immunopathol. 2017;39:215–23. Available from: CrossRefPubMedGoogle Scholar
  139. 139.
    Vénéreau E, Ceriotti C, Bianchi ME. DAMPs from cell death to new life. Front Immunol. 2015;6:422. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Thapa RJ, Ingram JP, Ragan KB, Nogusa S, Boyd DF, Benitez AA, et al. DAI senses influenza A virus genomic RNA and activates RIPK3-dependent cell death. Cell Host Microbe. 2016;20:674–81. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011;29:139–62. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Blériot C, Lecuit M. The interplay between regulated necrosis and bacterial infection. Cell Mol Life Sci. 2016;73:2369–78. Available from: CrossRefPubMedGoogle Scholar
  143. 143.
    Qiang X, Yang W-L, Wu R, Zhou M, Jacob A, Dong W, et al. Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis. Nat Med. 2013;19:1489–95. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Roumenina L. Personal communication.Google Scholar
  145. 145.
    Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I – molecular mechanisms of activation and regulation. Front Immunol. 2015;6:262. Available from: PubMedPubMedCentralGoogle Scholar
  146. 146.
    Schatz-Jakobsen JA, Yatime L, Larsen C, Petersen SV, Klos A, Andersen GR. Structural and functional characterization of human and murine C5a anaphylatoxins. Acta Crystallogr Sect D Biol Crystallogr. 2014;70:1704–17. Available from: CrossRefGoogle Scholar
  147. 147.
    Verschoor A, Karsten CM, Broadley SP, Laumonnier Y, Köhl J. Old dogs-new tricks: immunoregulatory properties of C3 and C5 cleavage fragments. Immunol Rev. 2016;274:112–26. Available from: CrossRefPubMedGoogle Scholar
  148. 148.
    Bajic G, Degn SE, Thiel S, Andersen GR. Complement activation, regulation, and molecular basis for complement-related diseases. EMBO J. 2015;34:2735–57. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Kolev M, Le Friec G, Kemper C. Complement—tapping into new sites and effector systems. Nat Rev Immunol. 2014;14:811–20. Available from: CrossRefPubMedGoogle Scholar
  150. 150.
    Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, Roumenina LT. Complement system part II: role in immunity. Front Immunol. 2015;6:257. Available from: PubMedPubMedCentralGoogle Scholar
  151. 151.
    Potempa M, Potempa J. Protease-dependent mechanisms of complement evasion by bacterial pathogens. Biol Chem. 2012;393:873–88. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Klos A, Wende E, Wareham KJ, Monk PN. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev. 2013;65:500–43. Available from: CrossRefPubMedGoogle Scholar
  153. 153.
    Klos A, Tenner AJ, Johswich K-O, Ager RR, Reis ES, Köhl J. The role of the anaphylatoxins in health and disease. Mol Immunol. 2009;46:2753–66. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    Ricklin D, Lambris JD. New milestones ahead in complement-targeted therapy. Semin Immunol. 2016;28:208–22. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Wong EKS, Kavanagh D. Anticomplement C5 therapy with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Transl Res. 2015;165:306–20. Available from: CrossRefPubMedGoogle Scholar
  156. 156.
    Jore MM, Johnson S, Sheppard D, Barber NM, Li YI, Nunn MA, et al. Structural basis for therapeutic inhibition of complement C5. Nat Struct Mol Biol. 2016;23:378–86. Available from: Scholar
  157. 157.
    Wehling C, Amon O, Bommer M, Hoppe B, Kentouche K, Schalk G, et al. Monitoring of complement activation biomarkers and eculizumab in complement-mediated renal disorders. Clin Exp Immunol. 2017;187:304–15. Available from: CrossRefPubMedGoogle Scholar
  158. 158.
    Heneka MT. Microglial demise and the progression of Alzheimer’s diseases. Cell death immune disorder. Leuven: European Conference; 2017.Google Scholar
  159. 159.
    Cai X, Xu H, Chen ZJ. Prion-like polymerization in immunity and inflammation. Cold Spring Harb Perspect Biol. 2017;9:a023580. Available from: Scholar
  160. 160.
    Bratton DL, Henson PM. Neutrophil clearance: when the party is over, clean-up begins. Trends Immunol. 2011;32:350–7. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  161. 161.
    O’Callaghan G, Houston A. Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets? Br J Pharmacol. 2015;172:5239–50. Available from: Scholar
  162. 162.
    Kawahara K, Hohjoh H, Inazumi T, Tsuchiya S, Sugimoto Y. Prostaglandin E2-induced inflammation: relevance of prostaglandin E receptors. Biochim Biophys Acta Mol Cell Biol Lipids. 2015;1851:414–21. Available from: CrossRefGoogle Scholar
  163. 163.
    Hangai S, Ao T, Kimura Y, Matsuki K, Kawamura T, Negishi H, et al. PGE2 induced in and released by dying cells functions as an inhibitory DAMP. Proc Natl Acad Sci U S A. 2016;113:3844–9. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    Koga K, Takaesu G, Yoshida R, Nakaya M, Kobayashi T, Kinjyo I, et al. Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c-Fos protein. Immunity. 2009;30:372–83. Available from: CrossRefPubMedGoogle Scholar
  165. 165.
    Sokolowska M, Chen L-Y, Liu Y, Martinez-Anton A, Qi H-Y, Logun C, et al. Prostaglandin E2 inhibits NLRP3 inflammasome activation through EP4 receptor and intracellular cyclic AMP in human macrophages. J Immunol. 2015;194:5472–87. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Lima KM, Vago JP, Caux TR, Negreiros-Lima GL, Sugimoto MA, Tavares LP, et al. The resolution of acute Inflammation induced by cyclic AMP is dependent on annexin A1. J Biol Chem. 2017;292(33):13758–73. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  167. 167.
    Perretti M, D’Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol. 2009;9:62–70. Available from: CrossRefPubMedGoogle Scholar
  168. 168.
    Gavins FNE, Hickey MJ. Annexin A1 and the regulation of innate and adaptive immunity. Front Immunol. 2012;3:354. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  169. 169.
    Sousa LP, Alessandri AL, Pinho V, Teixeira MM. Pharmacological strategies to resolve acute inflammation. Curr Opin Pharmacol. 2013;13:625–31. Available from: CrossRefPubMedGoogle Scholar
  170. 170.
    Sugimoto MA, Vago JP, Teixeira MM, Sousa LP. Annexin A1 and the resolution of inflammation: modulation of neutrophil recruitment, apoptosis, and clearance. J Immunol Res. 2016;2016:1–13. Available from: CrossRefGoogle Scholar
  171. 171.
    Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510:92–101. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  172. 172.
    Basil MC, Levy BD. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol. 2015;16:51–67. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    Serhan CN, Chiang N, Dalli J, Levy BD. Lipid mediators in the resolution of inflammation. Cold Spring Harb Perspect Biol. 2014;7:a016311. Available from: CrossRefPubMedGoogle Scholar
  174. 174.
    Anderson HA, Maylock CA, Williams JA, Paweletz CP, Shu H, Shacter E. Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol. 2003;4:87–91. Available from: CrossRefPubMedGoogle Scholar
  175. 175.
    Frasch SC, Bratton DL. Emerging roles for lysophosphatidylserine in resolution of inflammation. Prog Lipid Res. 2012;51:199–207. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  176. 176.
    Frasch SC, Fernandez-Boyanapalli RF, Berry KAZ, Murphy RC, Leslie CC, Nick JA, et al. Neutrophils regulate tissue neutrophilia in inflammation via the oxidant-modified lipid lysophosphatidylserine. J Biol Chem. 2013;288:4583–93. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Zagórska A, Través PG, Lew ED, Dransfield I, Lemke G. Diversification of TAM receptor tyrosine kinase function. Nat Immunol. 2014;15:920–8. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  178. 178.
    Franz S, Muñoz LE, Heyder P, Herrmann M, Schiller M. Unconventional apoptosis of polymorphonuclear neutrophils (PMN): staurosporine delays exposure of phosphatidylserine and prevents phagocytosis by MΦ-2 macrophages of PMN. Clin Exp Immunol. 2015;179:75–84. Available from: CrossRefPubMedGoogle Scholar
  179. 179.
    Griffiths HR, Gao D, Pararasa C. Redox regulation in metabolic programming and inflammation. Redox Biol. 2017;12:50–7. Available from: Scholar
  180. 180.
    Lemke G. Phosphatidylserine is the signal for TAM receptors and their ligands. Trends Biochem Sci. 2017;42:738–48. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Harris SG, Padilla J, Koumas L, Ray D, Phipps RP. Prostaglandins as modulators of immunity. Trends Immunol. 2002;23:144–50. Available from: CrossRefPubMedGoogle Scholar
  182. 182.
    Rodríguez M, Domingo E, Municio C, Alvarez Y, Hugo E, Fernández N, et al. Polarization of the innate immune response by prostaglandin E2: a puzzle of receptors and signals. Mol Pharmacol. 2014;85:187–97. Available from: CrossRefPubMedGoogle Scholar
  183. 183.
    Wang D, DuBois RN. Eicosanoids and cancer. Nat Rev Cancer. 2010;10:181–93. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  184. 184.
    Sousa LP, Lopes F, Silva DM, Tavares LP, Vieira AT, Rezende BM, et al. PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-kappaB-independent manner. J Leukoc Biol. 2010;87:895–904. Available from: CrossRefPubMedGoogle Scholar
  185. 185.
    Yan K, Gao L-N, Cui Y-L, Zhang Y, Zhou X. The cyclic AMP signaling pathway: exploring targets for successful drug discovery (review). Mol Med Rep. 2016;13:3715–23. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  186. 186.
    Sugimoto MA, Sousa LP, Pinho V, Perretti M, Teixeira MM. Resolution of inflammation: what controls its onset? Front Immunol. 2016;7:160. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  187. 187.
    Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, et al. International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev. 2009;61:119–61. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  188. 188.
    Li Y, Cai L, Wang H, Wu P, Gu W, Chen Y, et al. Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2. Oncogene. 2011;30:3887–99. Available from: CrossRefPubMedGoogle Scholar
  189. 189.
    Perucci LO, Sugimoto MA, Gomes KB, Dusse LM, Teixeira MM, Sousa LP. Annexin A1 and specialized proresolving lipid mediators: promoting resolution as a therapeutic strategy in human inflammatory diseases. Expert Opin Ther Targets. 2017;21:879–96. Available from: CrossRefPubMedGoogle Scholar
  190. 190.
    Pupjalis D, Goetsch J, Kottas DJ, Gerke V, Rescher U. Annexin A1 released from apoptotic cells acts through formyl peptide receptors to dampen inflammatory monocyte activation via JAK/STAT/SOCS signalling. EMBO Mol Med. 2011;3:102–14. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  191. 191.
    Weyd H, Abeler-Dörner L, Linke B, Mahr A, Jahndel V, Pfrang S, et al. Annexin A1 on the surface of early apoptotic cells suppresses CD8+ T cell immunity. PLoS One. 2013;e62449:8. Available from: Google Scholar
  192. 192.
    Kasuga K, Yang R, Porter TF, Agrawal N, Petasis NA, Irimia D, et al. Rapid appearance of resolvin precursors in inflammatory exudates: novel mechanisms in resolution. J Immunol. 2008;181:8677–87. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  193. 193.
    Dalli J, Serhan C. Macrophage proresolving mediators-the when and where. Microbiol Spectr. 2016;4 Available from:
  194. 194.
    Lemke G, Rothlin CV. Immunobiology of the TAM receptors. Nat Rev Immunol. 2008;8:327–36. Available from: CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Lemke G. Biology of the TAM receptors. Cold Spring Harb Perspect Biol. 2013;5:a009076. Available from: CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of StrasbourgMolecular ImmunoRheumatology, Laboratory of Excellence TransplantexStrasbourgFrance

Personalised recommendations