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Neutrophils, IL-1β, and gout: is there a link?

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Abstract

Gout is a prototype crystal-induced inflammatory disorder, characterized by neutrophil infiltration into inflamed joints. The identification of the role of NLRP3 inflammasome in the recognition of monosodium urate crystals and the subsequent release of IL-1β was a milestone in the elucidation of the pathogenesis of this disorder. IL-1β signaling is considered nowadays as the initiatory event that induces gouty inflammation and promotes the recruitment of vast numbers of neutrophils at the sites of inflammation. Crystal-induced neutrophil activation results in apoptosis inhibition, degranulation, superoxide production, cytokine release and, as recently described, formation of neutrophil extracellular traps, further amplifying the inflammatory process. Finally, neutrophil apoptosis and uptake of apoptotic material by macrophages drive the resolution of acute inflammation. In this review, we discuss the recent experimental data regarding the crosstalk between IL-1β and neutrophils in the pathogenesis of acute gout.

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References

  1. Roddy E, Doherty M (2010) Epidemiology of gout. Arthritis Res Ther 12:223

    Article  PubMed  Google Scholar 

  2. Annemans L, Spaepen E, Gaskin M et al (2008) Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000–2005. Ann Rheum Dis 67:960–966

    Article  PubMed  CAS  Google Scholar 

  3. Campion EW, Glynn RJ, DeLabry LO (1987) Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med 82:421–426

    Article  PubMed  CAS  Google Scholar 

  4. Terkeltaub R (2010) Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 6:30–38

    Article  PubMed  CAS  Google Scholar 

  5. Agudelo CA, Schumacher HR (1973) The synovitis of acute gouty arthritis. A light and electron microscopic study. Hum Pathol 4:265–279

    Article  PubMed  CAS  Google Scholar 

  6. Duncan H, Bluhm GB, Riddle JM et al (1968) Synovial urate crystals in acute gouty arthritis. A study of their origin and significance. Clin Orthop Relat Res 59:277–285

    Article  PubMed  CAS  Google Scholar 

  7. Malawista SE, de Boisfleury AC, Naccache PH (2011) Inflammatory gout: observations over a half-century. FASEB J 25:4073–4078

    Article  PubMed  CAS  Google Scholar 

  8. Mitroulis I, Skendros P, Ritis K (2010) Targeting IL-1beta in disease; the expanding role of NLRP3 inflammasome. Eur J Intern Med 21:157–163

    Article  PubMed  CAS  Google Scholar 

  9. Masters SL, Simon A, Aksentijevich I et al (2009) Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 27:621–668

    Article  PubMed  CAS  Google Scholar 

  10. Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550

    Article  PubMed  CAS  Google Scholar 

  11. Leemans JC, Cassel SL, Sutterwala FS (2011) Sensing damage by the NLRP3 inflammasome. Immunol Rev 243:152–162

    Article  PubMed  CAS  Google Scholar 

  12. Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832

    Article  PubMed  CAS  Google Scholar 

  13. Martinon F, Mayor A, Tschopp J (2009) The inflammasomes: guardians of the body. Annu Rev Immunol 27:229–265

    Article  PubMed  CAS  Google Scholar 

  14. Wang D, Zhang S, Li L et al (2010) Structural insights into the assembly and activation of IL-1β with its receptors. Nat Immunol 11:905–911

    Article  PubMed  CAS  Google Scholar 

  15. Gabay C, Lamacchia C, Palmer G (2010) IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol 6:232–241

    Article  PubMed  CAS  Google Scholar 

  16. Arend WP, Welgus HG, Thompson RC et al (1990) Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist. J Clin Invest 85:1694–1697

    Article  PubMed  CAS  Google Scholar 

  17. Colotta F, Dower SK, Sims JE et al (1994) The type II 'decoy' receptor: a novel regulatory pathway for interleukin 1. Immunol Today 15:562–566

    Article  PubMed  CAS  Google Scholar 

  18. Garlanda C, Anders HJ, Mantovani A (2009) TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization. Trends Immunol 30:439–446

    Article  PubMed  CAS  Google Scholar 

  19. Smith DE, Hanna R, Friend D et al (2003) The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action. Immunity 18:87–96

    Article  PubMed  CAS  Google Scholar 

  20. Duff GW, Atkins E, Malawista SE (1983) The fever of gout: urate crystals activate endogenous pyrogen production from human and rabbit mononuclear phagocytes. Trans Assoc Am Physicians 96:234–245

    PubMed  CAS  Google Scholar 

  21. di Giovine FS, Malawista SE, Thornton E (1991) Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mRNA and protein kinetics, and cellular distribution. J Clin Invest 87:1375–1381

    Article  PubMed  Google Scholar 

  22. Terkeltaub R, Zachariae C, Santoro D et al (1991) Monocyte-derived neutrophil chemotactic factor/interleukin-8 is a potential mediator of crystal-induced inflammation. Arthritis Rheum 34:894–903

    Article  PubMed  CAS  Google Scholar 

  23. Guerne PA, Terkeltaub R, Zuraw B et al (1989) Inflammatory microcrystals stimulate interleukin-6 production and secretion by human monocytes and synoviocytes. Arthritis Rheum 32:1443–1452

    Article  PubMed  CAS  Google Scholar 

  24. Yagnik DR, Hillyer P, Marshall D et al (2000) Noninflammatory phagocytosis of monosodium urate monohydrate crystals by mouse macrophages. Implications for the control of joint inflammation in gout. Arthritis Rheum 43:1779–1789

    Article  PubMed  CAS  Google Scholar 

  25. Landis RC, Yagnik DR, Florey O et al (2002) Safe disposal of inflammatory monosodium urate monohydrate crystals by differentiated macrophages. Arthritis Rheum 46:3026–3033

    Article  PubMed  CAS  Google Scholar 

  26. Martin WJ, Walton M, Harper J (2009) Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal-induced murine peritoneal model of acute gout. Arthritis Rheum 60:281–289

    Article  PubMed  Google Scholar 

  27. Roberge CJ, Grassi J, De Medicis R et al (1991) Crystal–neutrophil interactions lead to interleukin-1 synthesis. Agents Actions 34:38–41

    Article  PubMed  CAS  Google Scholar 

  28. Roberge CJ, de Medicis R, Dayer JM et al (1994) Crystal-induced neutrophil activation. V. Differential production of biologically active IL-1 and IL-1 receptor antagonist. J Immunol 152:5485–5494

    PubMed  CAS  Google Scholar 

  29. Liu-Bryan R, Scott P, Sydlaske A et al (2005) Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum 52:2936–2946

    Article  PubMed  CAS  Google Scholar 

  30. Scott P, Ma H, Viriyakosol S et al (2006) Engagement of CD14 mediates the inflammatory potential of monosodium urate crystals. J Immunol 177:6370–6378

    PubMed  CAS  Google Scholar 

  31. Chen CJ, Shi Y, Hearn A et al (2006) MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 116:2262–2271

    Article  PubMed  CAS  Google Scholar 

  32. Joosten LA, Netea MG, Mylona E et al (2010) Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1β production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheum 62:3237–3248

    Article  PubMed  CAS  Google Scholar 

  33. Mylona EE, Mouktaroudi M, Crisan TO et al (2012) Enhanced interleukin-1β production of PBMCs from patients with gout after stimulation with Toll-like receptor-2 ligands and urate crystals. Arthritis Res Ther 14:R158

    Article  PubMed  CAS  Google Scholar 

  34. Martinon F, Petrilli V, Mayor A et al (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241

    Article  PubMed  CAS  Google Scholar 

  35. Hornung V, Bauernfeind F, Halle A et al (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9:847–856

    Article  PubMed  CAS  Google Scholar 

  36. Amaral FA, Costa VV, Tavares LD et al (2012) NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout. Arthritis Rheum 64:474–484

    Article  PubMed  CAS  Google Scholar 

  37. Scanu A, Oliviero F, Ramonda R et al (2012) Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor β1 in the resolution phase. Ann Rheum Dis 71:621–624

    Article  PubMed  CAS  Google Scholar 

  38. Torres R, Macdonald L, Croll SD et al (2009) Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis. Ann Rheum Dis 68:1602–1608

    Article  PubMed  CAS  Google Scholar 

  39. Schlesinger N, Alten RE, Bardin T et al (2012) Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 71(11):1839–1849. doi:10.1136/annrheumdis-2011-200908

    Article  PubMed  CAS  Google Scholar 

  40. Schumacher HR Jr, Sundy JS, Terkeltaub R et al (2012) Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial. Arthritis Rheum 64:876–884

    Article  PubMed  CAS  Google Scholar 

  41. McGonagle D, Tan AL, Shankaranarayana S et al (2007) Management of treatment resistant inflammation of acute on chronic tophaceous gout with anakinra. Ann Rheum Dis 66:1683–1684

    Article  PubMed  CAS  Google Scholar 

  42. Dalbeth N, Pool B, Gamble GD et al (2010) Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum 62:1549–1556

    Article  PubMed  CAS  Google Scholar 

  43. Phelps P, McCarty DJ Jr (1966) Crystal-induced inflammation in canine joints. II. Importance of polymorphonuclear leukocytes. J Exp Med 124:115–126

    Article  PubMed  CAS  Google Scholar 

  44. Chang YH, Garalla EJ (1968) Suppression of urate crystal-induced canine joint inflammation by heterologous anti-polymorphonuclear leukocyte serum. Arthritis Rheum 11:145–150

    Article  PubMed  CAS  Google Scholar 

  45. Martin WJ, Harper JL (2010) Innate inflammation and resolution in acute gout. Immunol Cell Biol 88:15–19

    Article  PubMed  Google Scholar 

  46. Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6:173–182

    Article  PubMed  CAS  Google Scholar 

  47. Amulic B, Cazalet C, Hayes GL et al (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489

    Article  PubMed  CAS  Google Scholar 

  48. Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376

    Article  PubMed  CAS  Google Scholar 

  49. Williams MR, Azcutia V, Newton G et al (2011) Emerging mechanisms of neutrophil recruitment across endothelium. Trends Immunol 32:461–469

    Article  PubMed  CAS  Google Scholar 

  50. Chavakis T (2012) Leucocyte recruitment in inflammation and novel endogenous negative regulators thereof. Eur J Clin Invest 42:686–691

    Article  PubMed  CAS  Google Scholar 

  51. Pekin TJ Jr, Zvaifler NJ (1964) Hemolytic complement in synovial fluid. J Clin Invest 43:1372–1382

    Article  PubMed  CAS  Google Scholar 

  52. Hunder GG, McDuffie FC, Mullen BJ (1977) Activation of complement components C3 and factor B in synovial fluids. J Lab Clin Med 89:160–171

    PubMed  CAS  Google Scholar 

  53. Hasselbacher P (1979) Immunoelectrophoretic assay for synovial fluid C3 with correction for synovial fluid globulin. Arthritis Rheum 22:243–250

    Article  PubMed  CAS  Google Scholar 

  54. Giclas PC, Ginsberg MH, Cooper NR (1979) Immunoglobulin G independent activation of the classical complement pathway by monosodium urate crystals. J Clin Invest 63:759–764

    Article  PubMed  CAS  Google Scholar 

  55. Naff GB, Byers PH (1973) Complement as a mediator of inflammation in acute gouty arthritis.I. Studies on the reaction between human serum complement and sodium urate crystals. J Lab Clin Med 81:747–760

    PubMed  CAS  Google Scholar 

  56. Fields TR, Abramson SB, Weissmann G et al (1983) Activation of the alternative pathway of complement by monosodium urate crystals. Clin Immunol Immunopathol 26:249–257

    Article  PubMed  CAS  Google Scholar 

  57. Doherty M, Whicher JT, Dieppe PA (1983) Activation of the alternative pathway of complement by monosodium urate monohydrate crystals and other inflammatory particles. Ann Rheum Dis 42:285–291

    Article  PubMed  CAS  Google Scholar 

  58. Russell IJ, Mansen C, Kolb LM et al (1982) Activation of the fifth component of human complement (C5) induced by monosodium urate crystals: C5 convertase assembly on the crystal surface. Clin Immunol Immunopathol 24:239–250

    Article  PubMed  CAS  Google Scholar 

  59. Tramontini N, Huber C, Liu-Bryan R et al (2004) Central role of complement membrane attack complex in monosodium urate crystal-induced neutrophilic rabbit knee synovitis. Arthritis Rheum 50:2633–2639

    Article  PubMed  Google Scholar 

  60. Nishimura A, Akahoshi T, Takahashi M et al (1997) Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. J Leukoc Biol 62:444–449

    PubMed  CAS  Google Scholar 

  61. Terkeltaub R, Baird S, Sears P et al (1998) The murine homolog of the interleukin-8 receptor CXCR-2 is essential for the occurrence of neutrophilic inflammation in the air pouch model of acute urate crystal-induced gouty synovitis. Arthritis Rheum 41:900–909

    Article  PubMed  CAS  Google Scholar 

  62. Ryckman C, McColl SR, Vandal K et al (2003) Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis. Arthritis Rheum 48:2310–2320

    Article  PubMed  CAS  Google Scholar 

  63. Cybulsky MI, Chan MK, Movat HZ (1988) Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, and tumour necrosis factor and their implication in Gram-negative infection. Lab Invest 58:365–378

    PubMed  CAS  Google Scholar 

  64. Chapman PT, Yarwood H, Harrison AA et al (1997) Endothelial activation in monosodium urate monohydrate crystal-induced inflammation: in vitro and in vivo studies on the roles of tumor necrosis factor a and interleukin-1. Arthritis Rheum 40:955–965

    Article  PubMed  CAS  Google Scholar 

  65. Chapman PT, Jamar F, Harrison AA et al (1994) Noninvasive imaging of E-selectin expression by activated endothelium in urate crystal-induced arthritis. Arthritis Rheum 37:1752–1756

    Article  PubMed  CAS  Google Scholar 

  66. Chapman PT, Jamar F, Harrison AA et al (1996) Characterization of E-selectin expression, leukocyte traffic and clinical sequelae in urate crystal-induced inflammation: an insight into gout. Br J Rheumatol 35:323–334

    Article  PubMed  CAS  Google Scholar 

  67. Schumacher HR, Phelps P (1971) Sequential changes in human polymorphonuclear leukocytes after urate crystal phagocytosis. An electron microscopic study. Arthritis Rheum 14:513–526

    Article  PubMed  CAS  Google Scholar 

  68. Cherian PV, Schumacher HR Jr (1986) Immunochemical and ultrastructural characterization of serum proteins associated with monosodium urate crystals (MSU) in synovial fluid cells from patients with gout. Ultrastruct Pathol 10:209–219

    Article  PubMed  CAS  Google Scholar 

  69. Brandt KD (1974) The effect of synovial hyaluronate on the ingestion of monosodium urate crystals by leukocytes. Clin Chim Acta 55:307–315

    Article  PubMed  CAS  Google Scholar 

  70. Barabe F, Gilbert C, Liao N et al (1998) Crystal-induced neutrophil activation VI. Involvement of FcgammaRIIIB (CD16) and CD11b in response to inflammatory microcrystals. FASEB J 12:209–220

    PubMed  CAS  Google Scholar 

  71. Popa-Nita O, Marois L, Paré G et al (2008) Crystal-induced neutrophil activation: X. Proinflammatory role of the tyrosine kinase Tec. Arthritis Rheum 58:1866–1876

    Article  PubMed  CAS  Google Scholar 

  72. Desaulniers P, Fernandes M, Gilbert C et al (2001) Crystal-induced neutrophil activation. VII. Involvement of Syk in the responses to monosodium urate crystals. J Leukoc Biol 70:659–668

    PubMed  CAS  Google Scholar 

  73. Popa-Nita O, Proulx S, Paré G et al (2009) Crystal-induced neutrophil activation: XI. Implication and novel roles of classical protein kinase C. J Immunol 183:2104–2114

    Article  PubMed  CAS  Google Scholar 

  74. Popa-Nita O, Rollet-Labelle E, Thibault N et al (2007) Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia phosphatidylinositol 3-kinase. J Leukoc Biol 82:763–773

    Article  PubMed  CAS  Google Scholar 

  75. Mitroulis I, Kambas K, Chrysanthopoulou A et al (2011) Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One 6:e29318

    Article  PubMed  CAS  Google Scholar 

  76. Mantovani A, Cassatella MA, Costantini C et al (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531

    Article  PubMed  CAS  Google Scholar 

  77. Kaplan MJ, Radic M (2012) Neutrophil extracellular traps: double-edged swords of innate immunity. J Immunol 189:2689–2695

    Article  PubMed  CAS  Google Scholar 

  78. Popa-Nita O, Naccache PH (2010) Crystal-induced neutrophil activation. Immunol Cell Biol 88:32–40

    Article  PubMed  CAS  Google Scholar 

  79. Regan E, Flannelly J, Bowler R et al (2005) Extracellular superoxide dismutase and oxidant damage in osteoarthritis. Arthritis Rheum 52:3479–3491

    Article  PubMed  CAS  Google Scholar 

  80. Ross AD, Banda NK, Muggli M et al (2004) Enhancement of collagen-induced arthritis in mice genetically deficient in extracellular superoxide dismutase. Arthritis Rheum 50:3702–3711

    Article  PubMed  CAS  Google Scholar 

  81. Chia EW, Grainger R, Harper JL (2008) Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis: a rationale for use of low-dose colchicine. Br J Pharmacol 153:1288–1295

    Article  PubMed  CAS  Google Scholar 

  82. Naccache PH, Grimard M, Roberge CJ et al (1991) Crystal-induced neutrophil activation. I. Initiation and modulation of calcium mobilization and superoxide production by microcrystals. Arthritis Rheum 34:333–342

    Article  PubMed  CAS  Google Scholar 

  83. Abramson S, Hoffstein ST, Weissmann G (1982) Superoxide anion generation by human neutrophils exposed to monosodium urate. Arthritis Rheum 25:174–180

    Article  PubMed  CAS  Google Scholar 

  84. Martin WJ, Grainger R, Harrison A et al (2010) Differences in MSU-induced superoxide responses by neutrophils from gout subjects compared to healthy controls and a role for environmental inflammatory cytokines and hyperuricemia in neutrophil function and survival. J Rheumatol 37:1228–1235

    Article  PubMed  CAS  Google Scholar 

  85. Torres R, Macdonald L, Croll SD et al (2009) Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis. Ann Rheum Dis 68:1602–1608

    Article  PubMed  CAS  Google Scholar 

  86. Foell D, Wittkowski H, Vogl T et al (2007) S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J Leukoc Biol 81:28–37

    Article  PubMed  CAS  Google Scholar 

  87. Ryckman C, Gilbert C, de Médicis R et al (2004) Monosodium urate monohydrate crystals induce the release of the proinflammatory protein S100A8/A9 from neutrophils. J Leukoc Biol 76:433–40

    Article  PubMed  CAS  Google Scholar 

  88. Liu R, Aupperle K, Terkeltaub R (2001) Src family protein tyrosine kinase signaling mediates monosodium urate crystal-induced IL-8 expression by monocytic THP-1 cells. J Leukoc Biol 70:961–968

    PubMed  CAS  Google Scholar 

  89. Hachicha M, Naccache PH, McColl SR (1995) Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: a possible mechanism of neutrophil recruitment to sites of inflammation in synovitis. J Exp Med 182:2019–2025

    Article  PubMed  CAS  Google Scholar 

  90. Schlesinger N, Thiele RG (2010) The pathogenesis of bone erosions in gouty arthritis. Ann Rheum Dis 69:1907–1912

    Article  PubMed  CAS  Google Scholar 

  91. Braun T, Zwerina J (2011) Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Res Ther 13:235

    Article  PubMed  CAS  Google Scholar 

  92. Poubelle PE, Chakravarti A, Fernandes MJ et al (2007) Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils. Arthritis Res Ther 9:R25

    Article  PubMed  CAS  Google Scholar 

  93. Allaeys I, Rusu D, Picard S et al (2011) Osteoblast retraction induced by adherent neutrophils promotes osteoclast bone resorption: implication for altered bone remodeling in chronic gout. Lab Invest 91:905–920

    Article  PubMed  CAS  Google Scholar 

  94. Bratton DL, Henson PM (2011) Neutrophil clearance: when the party is over, clean-up begins. Trends Immunol 32:350–357

    Article  PubMed  CAS  Google Scholar 

  95. Scarlatti F, Granata R, Meijer AJ et al (2009) Does autophagy have a license to kill mammalian cells? Cell Death Differ 16:12–20

    Article  PubMed  CAS  Google Scholar 

  96. Mitroulis I, Kourtzelis I, Kambas K et al (2010) Regulation of the autophagic machinery in human neutrophils. Eur J Immunol 40:1461–1472

    Article  PubMed  CAS  Google Scholar 

  97. Yipp BG, Petri B, Salina D et al (2012) Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med 18(9):1386–1393. doi:10.1038/nm.2847

    Article  PubMed  CAS  Google Scholar 

  98. Labbé K, Saleh M (2008) Cell death in the host response to infection. Cell Death Differ 15:1339–1349

    Article  PubMed  CAS  Google Scholar 

  99. Tudan C, Fong D, Duronio V et al (2000) The inhibition of spontaneous and tumor necrosis factor-alpha induced neutrophil apoptosis by crystals of calcium pyrophosphate dihydrate and monosodium urate monohydrate. J Rheumatol 27:2463–2472

    PubMed  CAS  Google Scholar 

  100. Akahoshi T, Nagaoka T, Namai R et al (1997) Prevention of neutrophil apoptosis by monosodium urate crystals. Rheumatol Int 16:231–235

    Article  PubMed  CAS  Google Scholar 

  101. Rose DM, Sydlaske AD, Agha-Babakhani A et al (2006) Transglutaminase limits murine peritoneal acute gout-like inflammation by regulating macrophage clearance of apoptotic neutrophils. Arthritis Rheum 54:3363–3371

    Article  PubMed  CAS  Google Scholar 

  102. Fadok VA, Bratton DL, Konowal A et al (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898

    Article  PubMed  CAS  Google Scholar 

  103. Steiger S, Harper JL (2012) Neutrophil cannibalism triggers TGF-β1 production and self-regulation of neutrophil inflammatory function in MSU crystal-induced inflammation. Arthritis Rheum. doi:10.1002/art.37822

  104. Shirahama T, Cohen AS (1974) Ultrastructural evidence for leakage of lysosomal contents after phagocytosis of monosodium urate crystals. A mechanism of gouty inflammation. Am J Pathol 76:501–520

    PubMed  CAS  Google Scholar 

  105. Remijsen Q, Vanden Berghe T, Wirawan E et al (2011) Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res 21:290–304

    Article  PubMed  CAS  Google Scholar 

  106. Kambas K, Mitroulis I, Apostolidou E et al (2012) Autophagy mediates the delivery of thrombogenic tissue factor to neutrophil extracellular traps in human sepsis. PLoS One 7:e45427

    Article  PubMed  CAS  Google Scholar 

  107. Guma M, Ronacher L, Liu-Bryan R et al (2009) Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum 60:3642–3650

    Article  PubMed  CAS  Google Scholar 

  108. Joosten LA, Netea MG, Fantuzzi G et al (2009) Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum 60:3651–3662

    Article  PubMed  CAS  Google Scholar 

  109. Coeshott C, Ohnemus C, Pilyavskaya A et al (1999) Converting enzyme-independent release of tumor necrosis factor α and IL-1β from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. Proc Natl Acad Sci U S A 96:6261–6266

    Article  PubMed  CAS  Google Scholar 

  110. Mankan AK, Dau T, Jenne D et al (2012) The NLRP3/ASC/caspase-1 axis regulates IL-1β processing in neutrophils. Eur J Immunol 42:710–715

    Article  PubMed  CAS  Google Scholar 

  111. Watson RWG, Rotstein OD, Parodo J et al (1998) The IL-1b-converting enzyme (caspase-1) inhibits apoptosis of inflammatory neutrophils through activation of IL-1b. J Immunol 161:957–962

    PubMed  CAS  Google Scholar 

  112. Schorn C, Janko C, Latzko M et al (2012) Monosodium urate crystals induce extracellular DNA traps in neutrophils, eosinophils, and basophils but not in mononuclear cells. Front Immun 3:277

    Google Scholar 

  113. Schorn C, Janko C, Krenn V et al (2012) Bonding the foe—NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals. Front Immunol 3:376

    PubMed  Google Scholar 

  114. Clark SR, Ma AC, Tavener SA et al (2007) Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 13:463–469

    Article  PubMed  CAS  Google Scholar 

  115. Tillack K, Breiden P, Martin R et al (2012) T lymphocyte priming by neutrophil extracellular traps links innate and adaptive immune responses. J Immunol 188:3150–3159

    Article  PubMed  CAS  Google Scholar 

  116. Sangaletti S, Tripodo C, Chiodoni C et al (2012) Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells towards ANCA induction and associated autoimmunity. Blood 120:3007–3018

    Article  PubMed  CAS  Google Scholar 

  117. Saffarzadeh M, Juenemann C, Queisser MA et al (2012) Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One 7:e32366

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This review was supported by the Hellenic Ministry of Education and General Secretariat for Research and Technology (ESPA project/No 898).

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Authors and Affiliations

  1. First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Dragana, Alexandroupoli, Greece

    Ioannis Mitroulis, Konstantinos Kambas & Konstantinos Ritis

  2. Department of Internal Medicine III, Division of Vascular Inflammation, Diabetes and Kidney, University Clinic Carl-Gustav-Carus, University of Dresden, Dresden, Germany

    Ioannis Mitroulis

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  1. Ioannis Mitroulis
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  2. Konstantinos Kambas
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Correspondence to Konstantinos Ritis.

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This article is a contribution to the special issue on Neutrophils - Guest Editors: Paul Hasler and Sinuhe Hahn.

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Video clip Reconstruction of single plane images of cells presented in Fig. 3 in a video clip. Neutrophils were incubated with synovial fluid from patients with gout as described in Fig. 3. The formation of LC3B (red) and p62 (green) double positive structures suggests the activation of autophagy. Nuclear staining with DAPI (WMV 5435 kb)

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Mitroulis, I., Kambas, K. & Ritis, K. Neutrophils, IL-1β, and gout: is there a link?. Semin Immunopathol 35, 501–512 (2013). https://doi.org/10.1007/s00281-013-0361-0

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  • DOI: https://doi.org/10.1007/s00281-013-0361-0

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