[en] OBJECTIVE: Gouty arthritis is caused by the precipitation of monosodium urate monohydrate (MSU) crystals in the joints. While it has been reported that mast cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs during acute attacks of gout. This study was undertaken to assess the role of MCs in a mouse model of MSU crystal-induced acute arthritis. METHODS: We assessed the effects of intraarticular (IA) injection of MSU crystals in various strains of mice with constitutive or inducible MC deficiency or in mice lacking interleukin-1beta (IL-1beta) or other elements of innate immunity. We also assessed the response to IA injection of MSU crystals in genetically MC-deficient mice after IA engraftment of wild-type or IL-1beta(-/-) bone marrow-derived cultured MCs. RESULTS: MCs were found to augment acute tissue swelling following IA injection of MSU crystals in mice. IL-1beta production by MCs contributed importantly to MSU crystal-induced tissue swelling, particularly during its early stages. Selective depletion of synovial MCs was able to diminish MSU crystal-induced acute inflammation in the joints. CONCLUSION: Our findings identify a previously unrecognized role of MCs and MC-derived IL-1beta in the early stages of MSU crystal-induced acute arthritis in mice.
Disciplines :
Life sciences: Multidisciplinary, general & others
Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al, for the National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008; 58: 26-35.
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J,. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440: 237-41.
Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 2006; 116: 2262-71.
Abraham SN, St John AL,. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 2010; 10: 440-52.
Nigrovic PA, Binstadt BA, Monach PA, Johnsen A, Gurish M, Iwakura Y, et al. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A 2007; 104: 2325-30.
Schumacher HR Jr, Sundy JS, Terkeltaub R, Knapp HR, Mellis SJ, Stahl N, et al, on behalf of the 0619 Study Group. 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 2012; 64: 876-84.
Piliponsky AM, Chen CC, Grimbaldeston MA, Burns-Guydish SM, Hardy J, Kalesnikoff J, et al. Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice. Am J Pathol 2010; 176: 926-38.
Wada T, Ishiwata K, Koseki H, Ishikura T, Ugajin T, Ohnuma N, et al. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J Clin Invest 2010; 120: 2867-75.
Horai R, Asano M, Sudo K, Kanuka H, Suzuki M, Nishihara M, et al. Production of mice deficient in genes for interleukin (IL)-1α, IL-1β, IL-1α/β, and IL-1 receptor antagonist shows that IL-1β is crucial in turpentine-induced fever development and glucocorticoid secretion. J Exp Med 1998; 187: 1463-75.
Korner H, Cook M, Riminton DS, Lemckert FA, Hoek RM, Ledermann B, et al. Distinct roles for lymphotoxin-α and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue. Eur J Immunol 1997; 27: 2600-9.
Lilla JN, Chen CC, Mukai K, BenBarak MJ, Franco CB, Kalesnikoff J, et al. Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice. Blood 2011; 118: 6930-8.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-24.
Ferrer M, Nunez-Cordoba JM, Luquin E, Grattan CE, De la Borbolla JM, Sanz ML, et al. Serum total tryptase levels are increased in patients with active chronic urticaria. Clin Exp Allergy 2010; 40: 1760-6.
Reber LL, Marichal T, Galli SJ,. New models for analyzing mast cell functions in vivo. Trends Immunol 2012; 33: 613-25.
Zhou JS, Xing W, Friend DS, Austen KF, Katz HR,. Mast cell deficiency in KitW-sh mice does not impair antibody-mediated arthritis. J Exp Med 2007; 204: 2797-802.
Hershko AY, Suzuki R, Charles N, Alvarez-Errico D, Sargent JL, Laurence A, et al. Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. Immunity 2011; 35: 562-71.
Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam SY, Galli SJ,. Mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol 2005; 167: 835-48.
Reber LL, Marichal T, Mukai K, Kita Y, Tokuoka SM, Roers A, et al. Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice. J Allergy Clin Immunol 2013; 132: 881-888.e11.
Strowig T, Henao-Mejia J, Elinav E, Flavell R,. Inflammasomes in health and disease. Nature 2012; 481: 278-86.
Schroder K, Zhou R, Tschopp J,. The NLRP3 inflammasome: a sensor for metabolic danger? Science 2010; 327: 296-300.
Nigrovic PA, Lee DM,. Synovial mast cells: role in acute and chronic arthritis. Immunol Rev 2007; 217: 19-37.
Schwartz LB, Min HK, Ren S, Xia HZ, Hu J, Zhao W, et al. Tryptase precursors are preferentially and spontaneously released, whereas mature tryptase is retained by HMC-1 cells, Mono-Mac-6 cells, and human skin-derived mast cells. J Immunol 2003; 170: 5667-73.
Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V,. Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy 2013; 33: 744-53.
So A, De Smedt T, Revaz S, Tschopp J,. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 2007; 9: R28.
Lee SJ, Nam KI, Jin HM, Cho YN, Lee SE, Kim TJ, et al. Bone destruction by receptor activator of nuclear factor κB ligand-expressing T cells in chronic gouty arthritis. Arthritis Res Ther 2011; 13: R164.
Schiltz C, Liote F, Prudhommeaux F, Meunier A, Champy R, Callebert J, et al. Monosodium urate monohydrate crystal-induced inflammation in vivo: quantitative histomorphometric analysis of cellular events. Arthritis Rheum 2002; 46: 1643-50.
Getting SJ, Flower RJ, Parente L, de Medicis R, Lussier A, Woliztky BA, et al. Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins. J Pharmacol Exp Ther 1997; 283: 123-30.
Feyerabend TB, Weiser A, Tietz A, Stassen M, Harris N, Kopf M, et al. Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity 2011; 35: 832-44.
Lee DM, Friend DS, Gurish MF, Benoist C, Mathis D, Brenner MB,. Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 2002; 297: 1689-92.
Amaral FA, Costa VV, Tavares LD, Sachs D, Coelho FM, Fagundes CT, et al. NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B4 in a murine model of gout. Arthritis Rheum 2012; 64: 474-84.
Joosten LA, Netea MG, Mylona E, Koenders MI, Malireddi RK, Oosting M, et al. 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 2010; 62: 3237-48.
Gross O, Yazdi AS, Thomas CJ, Masin M, Heinz LX, Guarda G, et al. Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 2012; 36: 388-400.
Hoffman HM, Scott P, Mueller JL, Misaghi A, Stevens S, Yancopoulos GD, et al. Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal-induced inflammation in mice. Arthritis Rheum 2010; 62: 2170-9.
Franchi L, Kanneganti TD, Dubyak GR, Nunez G,. Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria. J Biol Chem 2007; 282: 18810-8.
Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nat Med 2009; 15: 1170-8.
Cho JS, Guo Y, Ramos RI, Hebroni F, Plaisier SB, Xuan C, et al. Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice. PLoS Pathog 2012; 8: e1003047.
Martin WJ, Walton M, Harper J,. Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal-induced murine peritoneal model of acute gout. Arthritis Rheum 2009; 60: 281-9.
Nakamura Y, Franchi L, Kambe N, Meng G, Strober W, Nunez G,. Critical role for mast cells in interleukin-1β-driven skin inflammation associated with an activating mutation in the nlrp3 protein. Immunity 2012; 37: 85-95.
Nakamura Y, Kambe N, Saito M, Nishikomori R, Kim YG, Murakami M, et al. Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria. J Exp Med 2009; 206: 1037-46.
Gaudenzio N, Laurent C, Valitutti S, Espinosa E,. Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype. J Allergy Clin Immunol 2013; 131: 1400-7.e11.
Buckley MG, Walters C, Wong WM, Cawley MI, Ren S, Schwartz LB, et al. Mast cell activation in arthritis: detection of α- and β-tryptase, histamine and eosinophil cationic protein in synovial fluid. Clin Sci (Lond) 1997; 93: 363-70.
Malone DG, Irani AM, Schwartz LB, Barrett KE, Metcalfe DD,. Mast cell numbers and histamine levels in synovial fluids from patients with diverse arthritides. Arthritis Rheum 1986; 29: 956-63.
Sampson D, Archer GT,. Release of histamine from human basophils. Blood 1967; 29: 722-36.
Xu X, Zhang D, Zhang H, Wolters PJ, Killeen NP, Sullivan BM, et al. Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. J Exp Med 2006; 203: 2907-17.
Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T,. Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. New Engl J Med 1987; 316: 1622-6.
Dalbeth N,. Gout in 2010: progress and controversies in treatment. Nat Rev Rheumatol 2011; 7: 77-8.
Rock KL, Kataoka H, Lai JJ,. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol 2013; 9: 13-23.