Pathogenesis of Monosodium Urate Crystal-Induced Inflammation

  • R. Terkeltaub
Conference paper


Acute articular and periarticular inflammation and chronic articular destructive changes are well-recognized consequences of the deposition, in articular and periarticular tissues, of crystals of the monosodium salt of uric acid (MSU). MSU crystals directly or indirectly activate a remarkable number of humoral and cellular inflammatory mediator systems, and this is reflected in the clinical features of a typical acute gouty paroxysm, i. e., acute onset, severe pain, edema and erythema extending beyond the joint margin, neutro-phil influx and activation, and systemic manifestations. In this chapter, our current understanding of the pathogenesis of MSU-crystal-associated inflammation is reviewed.


Neutrophil Activation Acute Gout Urate Crystal Monosodium Urate Acute Gouty Arthritis 
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  1. Aderka D, Le J, Vilcek J (1989) IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol 143: 3517–3523PubMedGoogle Scholar
  2. Agudelo C, Schumacher HR (1973) The synovitis of acute gouty arthritis. A light and electron microscopic study. Hum Pathol 4: 265–269PubMedCrossRefGoogle Scholar
  3. Arend WP, Dayer J-M (1990) Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum 33: 305–315PubMedCrossRefGoogle Scholar
  4. Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide-1/interleukin-8, a novel cytokine that activates neutrophils. J Clin Invest 84: 1045–1049PubMedCrossRefGoogle Scholar
  5. Bhatt A, Spilberg I (1988) Purification of crystal induced chemotactic factor from human neutrophils. Clinical Biochem 21: 341–345CrossRefGoogle Scholar
  6. Bomalaski JS, Baker DG, Brophy LM, Clark MA (1990) Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein. J Immunol (In press)Google Scholar
  7. Camussi G, Tetta C, Bussolino F, Baglioni C (1990) Antiinflammatory peptides (antiinflammins) inhibit synthesis of platelet-activating factor, neutrophil aggregation, and chemotaxis, and intradermal inflammatory reactions. J Exp Med 171: 913–927PubMedCrossRefGoogle Scholar
  8. Colditz, IG, Movat HZ (1984) Desensitization of acute inflammatory lesions to chemotaxins and endotoxin. J Immunol 133: 2163–2168PubMedGoogle Scholar
  9. Di Giovine FS, Malawista SE, Nuki G, Duff GW (1987) Interleukin-1 (IL-1) as amediator of crystal arthritis: stimulation of T cell and synovoal fibroblast mito-genesis by urate crystal-induced IL-l. J Immunol 138: 3213–3218PubMedGoogle Scholar
  10. Doherty M, Whicher JT, Dieppe PA (1983) Activation of the alternative pathway complement by monosodium urate monohydrate crystals and other inflammatory particles. Ann Rheum Dis 42: 285–291PubMedCrossRefGoogle Scholar
  11. Giclas PC, Ginsberg MH, and Cooper NR (1979) Immunoglobulin G independent activation of the classical complement pathway by monosodium urate crystals. J Clin Invest 63: 759–765PubMedCrossRefGoogle Scholar
  12. Ginsberg MH, Jaques B, Cochrane CG, Griffin JH (1980) Urate crystal-dependent cleavage of Hageman factor in human plasma and synovial fluid. J Lab Clin Med 95: 497–506PubMedGoogle Scholar
  13. Gordon TP, Roberts-Thompson PJ (1986). Preliminary evidence for the presence of an inhibitor on the surface of natural monosodium urate crystals. Arthritis Rheum 29: 1172–1173PubMedCrossRefGoogle Scholar
  14. Guerne PA, Terkeltaub R, Zuraw B, Lotz M (1989) Stimulation of IL-6 production in human monocytes and synoviocytes by inflammatory microcrystals. Arthritis Rheum 32: 1443–1452PubMedCrossRefGoogle Scholar
  15. Hannum CH, Wilcox CJ, Arend WP, Joslin FG, Dripps DJ, Heimdal PL, Armes LG, Sommer A, Eisenberg SP, Thompson RC (1990) Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature 343: 336–340PubMedCrossRefGoogle Scholar
  16. Haslett, C, Jose PJ, Giclas PC, Williams TJ, Henson PM (1989) Cessation of neutro-phil influx in C5a-induced acute experimental arthritis is associated with loss of chemoattractant activity from the joint space. J Immunol 142: 3510–3517PubMedGoogle Scholar
  17. Herring FG, Lam E, Burt HM (1986) A spin label study of the membranolytic effects of crystalline monosodium urate monohydrate. J Rheumatol 13: 623–630PubMedGoogle Scholar
  18. Huizinga TWJ, de Haas M, Kleijer M, Nuijens JH, Roos D, von den Borne AEG (1990) Soluble Fc gamma Receptor III in human plasma originates from release by neutrophils. J Clin Invest 86: 416–423PubMedCrossRefGoogle Scholar
  19. Krutmann J, Kirnbauer R, Kock A, Schwarz T, Schopf E, May LT, Sehgal PB, Luger TA (1990) Cross-linking Fc receptors on monocytes triggers IL-6 production. Role in anti-CD3-induced T cell activation. J Immunol 145: 1337–1342PubMedGoogle Scholar
  20. Jaques BC, Ginsberg MH (1982) The role of cell surface proteins in platelet stimulation by monosodium urate crystals. Arthritis Rheum 25: 508–521PubMedCrossRefGoogle Scholar
  21. Kimberly RP, Ahlstrom JW, Click ME, Edberg JC (1990) The glycosyl phosphatidylinositol-linked FcgammaRIIIpMN mediates transmembrane signalling events distinct from FcgammaRll. J Exp Med 171: 1239–1255PubMedCrossRefGoogle Scholar
  22. Lotz, Carson D, Vaughan J (1987) Substance P activation of rheumatoid synoviocytes: Neural pathway in pathogenesis of arthritis. Science 235: 893–895PubMedCrossRefGoogle Scholar
  23. Mandel NS (1976) The structural basis of crystal-induced membranolysis. Arthritis Rheum 19: 439–455PubMedCrossRefGoogle Scholar
  24. McCarthy GM, Barthelemy CR, Veum JA, and Wortmann RL (1990) Influence of antihyperuricemic therapy on the clinical and radiographic progression of gout. Arthritis Rheum 33: S54Google Scholar
  25. Onello E, Traynor-Kaplan A, Sklar L, Terkeltaub R (1991) Mechanism of neutrophil activation by an unopsonited inflammatory particulate. Arthritis Rheum, in pressGoogle Scholar
  26. Ortiz-Bravo E, Clayburne G, Sieck M, Rothfuss S, Schumacher HR (1990) Immunolabeling of proteins coating monosodium urate(MSU) crystals in sequential samples from acute gouty arthritis and MSU induced inflammation in the rat subcutaneous air pouch. Arthritis Rheum 33: S55Google Scholar
  27. Perl-Treves D, Addadi L (1988) A structural approach to pathological crystallizations. Gout: the possible role of albumin in sodium urate crystallization. Proc R Soc Lond 235: 145–159PubMedCrossRefGoogle Scholar
  28. Phelps P and McCarty DJ (1966) Crystal-induced inflammation in canine joints. II. Importance of polymorphonuclear leukocytes. J Exp Med 124 (1): 150CrossRefGoogle Scholar
  29. Porteau F, Nathan C (1990) Shedding of tumor necrosis factor receptors by activated human neutrophils. J Exp Med 172: 599–607CrossRefGoogle Scholar
  30. Rosen MS, Baker DG, Schumacher HR, Cherian PV (1986) Products of polymorphonuclear cell injury inhibit IgG enhancement of monosodium urate-induced superoxide production. Arthritis Rheum 29: 1473–1479PubMedCrossRefGoogle Scholar
  31. Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, and Haslett C (1989) Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J Clin Invest 83: 865–875PubMedCrossRefGoogle Scholar
  32. Serhan CN, Lundberg U, Weissmann G Samuelsson B (1984) Formation of leukotrienes and hydroxy acids by human neutrophils and platelets exposed to monosodium urate. Prostaglandins 17: 563–581CrossRefGoogle Scholar
  33. Spilberg I, Mandell B (1982) Crystal-induced chemotactic factor. In: Weissmann G (ed) Advances in Inflammation Research, vol 5. Raven Press, New York, pp 57–65Google Scholar
  34. Streiter RM, Chensue SW, Standiford TJ, Basha MA, Showell HI, Kunkel SL (1990) Disparate gene expression of chemotactic cytokines by human mononuclear phagocytes. Biochem Biophys Res Comm 166: 886–891CrossRefGoogle Scholar
  35. Terkeltaub R, Curtiss LK, Tenner Ai, Ginsberg MH (1984) Lipoproteins containing apolipoprotein B are a major regulator of neutrophil responses to monosodium urate crystals. J Clin Invest 73: 1719–1725PubMedCrossRefGoogle Scholar
  36. Terkeltaub R, Dyer C, Martin J, Curtiss LK (1990a) Apolipoprotein E (apo E) inhibits the capacity of monosodium urate crystals to stimulate neutrophils: Characterization of intraarticular apo E and demonstration of apo E binding to urate crystals in vivo. J Clin Invest (In press)Google Scholar
  37. Terkeltaub R, Ginsberg M, McCarty DJ (1989) Pathogenesis and treatment of crystal-induced inflammation. In: McCarty DJ (ed) Arthritis and Allied Conditions. Lea and Febiger, Philadelphia, pp 1691–1710Google Scholar
  38. Terkeltaub R, Martin J, Curtiss LK, Ginsberg M (1986a) Apolipoprotein B mediates the capacity of low density lipoprotein to suppress neutrophil stimulation of particulates. J Biol Chem 261: 15662–15667Google Scholar
  39. Terkeltaub R, Sklar LA, Mueller H (1990b) Neutrophil activation by inflammatory microcrystals of monosodium urate monohydrate utilizes pertussis toxin-insensitive and sensitive pathways. J Immunol 144: 2719–2724Google Scholar
  40. Terkeltaub R, Smeltzer D, Curtiss L, Ginsberg M (1986b) Low density lipoprotein inhibits the physical interaction of phlogistic crystals and inflammatory cells. Arthritis and Rheumatism 29: 363–369CrossRefGoogle Scholar
  41. Terkeltaub R, Zachariae C, Santoro D, Martin J, Peveri P, Matsushima K (1991) Monocyte-derived neutrophil chemotactic factor/IL-8 is a potential mediator of crystal-induced inflammation. Arthritis Rheum, in pressGoogle Scholar
  42. Webb DSA, Shimizu Y, Gizs AA, Seventer V, Shaw S, Gerrard TL (1990) LFA-3, CD44, and CD45: Physiologic triggers of human monocyte TNF and IL-1 release. Science 249: 1295–1297PubMedCrossRefGoogle Scholar
  43. Weissmann G, Rita GA (1972) Molecular basis of gouty inflammation: Interaction of monosodium urate crystals with lysosomes and liposomes. Nature [New Biol] 240: 167–172CrossRefGoogle Scholar

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© Springer Verlag, Berlin Heidelberg 1991

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  • R. Terkeltaub

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