Urate Monohydrate Crystals (urate + monohydrate_crystal)

Distribution by Scientific Domains

Kinds of Urate Monohydrate Crystals

  • monosodium urate monohydrate crystal

  • Selected Abstracts

    Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal,induced murine peritoneal model of acute gout

    ARTHRITIS & RHEUMATISM, Issue 1 2009
    William John Martin
    Objective To determine whether infiltrating monocytes, neutrophils, or resident macrophages contribute to the early inflammatory response to monosodium urate monohydrate (MSU) crystals in vivo. Methods MSU crystal,induced inflammation was monitored using a peritoneal model of acute gout. The production of proinflammatory cytokines (interleukin-1, [IL-1,], tumor necrosis factor , [TNF,], IL-6) by resident macrophages, infiltrating monocytes, and neutrophils during the onset of gout was determined by flow cytometry. Infiltrating and resident peritoneal cells were cultured with MSU crystals ex vivo, and proinflammatory cytokine production was determined by multiplex cytokine array. Activated macrophages on the visceral epithelial lining of the peritoneum were identified by immunofluorescence histochemistry. The inflammatory immune response to MSU crystals was then compared with the inflammatory response in mice depleted of resident macrophages by pretreatment with clodronate liposomes. Results The production of cytokines in vivo preceded the influx of Gr-1intermediate7/4+ monocytes. Monocytes and neutrophils recruited during the inflammatory phase of the response to MSU crystals failed to produce proinflammatory cytokines either in vivo, or ex vivo following restimulation with MSU crystals. Stimulation of the naive peritoneal resident cell population with MSU crystals ex vivo resulted in positive staining of resident macrophages for the proinflammatory cytokines IL-1,, TNF,, and IL-6. Depletion of the resident macrophage population resulted in a significant decrease in both MSU crystal,induced neutrophil infiltration and proinflammatory cytokine production in vivo despite the presence of infiltrating monocytes. Conclusion These data indicate that resident macrophages, rather than infiltrating monocytes or neutrophils, are important for initiating and driving the early proinflammatory phase of acute gout. [source]

    Monosodium urate monohydrate crystal,induced inflammation in vivo: Quantitative histomorphometric analysis of cellular events

    ARTHRITIS & RHEUMATISM, Issue 6 2002
    C. Schiltz
    Objective To quantify the inflammatory cell response in rat air pouch pseudosynovial membrane during monosodium urate monohydrate (MSU) crystal,induced inflammation. Methods In the rat air-pouch model, we used a computer-assisted histomorphometric method to quantify cell distributions, based on cell linear densities, in histologic sections of membranes from pouches injected with MSU or saline. The volume, white blood cell (WBC) count, and histamine content of the pouch exudates were determined at several time points. Results Injection of 10 mg of MSU crystals into the pouch produced an acute exudate. After peaking at 24 hours, the exudate volume and WBC count decreased spontaneously over the next 3 days, simulating the self-limited course of acute gout. Membrane thickness followed a parallel course. Membrane polymorphonuclear cell (PMN) linear densities were closely correlated with exudate WBC counts, suggesting PMN recruitment from the subintimal synovial membrane. Both monocyte/macrophage and mast cell linear densities increased in the subintimal layer 2 hours after crystal injection (P = 0.038 and P = 0.03, respectively, versus controls), whereas PMN linear densities showed 2 peaks, one at 4 hours and the other 24 hours. The exudate histamine content peaked 6 hours after crystal injection, when mast cell linear densities were minimal in the membranes, suggesting mast cell degranulation. Conclusion An increase in monocyte/macrophage and mast cell densities in the membrane preceded the PMN influx in the pouch membrane and exudate, suggesting that mast cells may be involved in the early phase of MSU crystal,induced inflammation, at least in this rat model. [source]

    REVIEW: Management of gout: beyond allopurinol

    N. W. McGill
    Abstract The basic concepts of the pathogenesis and management of gout have not altered for many years. Monosodium urate monohydrate crystals drive the disease and identification of these crystals is required for certain diagnosis. In contrast, our understanding of the mediators of gouty inflammation, the appropriate target serum urate concentration during treatment, the drugs available and the best ways to use those drugs have all advanced in recent years and will be the focus of this review. [source]

    Cellular characterization of the gouty tophus: A quantitative analysis

    ARTHRITIS & RHEUMATISM, Issue 5 2010
    Nicola Dalbeth
    Objective To characterize the cellular architecture of the tophus and to determine the presence of cytokines implicated in the initiation and resolution of gouty inflammation. Methods Sixteen fixed, paraffin-embedded, uninfected tophus samples were surgically obtained from 12 patients with microscopically proven gout and were analyzed by quantitative immunohistochemistry. The number of cells present in the corona and fibrovascular zones of the tophus was analyzed by Genmod mixed models analysis. Results Numerous CD68+ mononucleated and multinucleated cells were present within the corona zone. Mast cells were identified in all tophus samples and at similar densities throughout the corona and fibrovascular zones. In contrast, neutrophils were rarely observed. Plasma cells were present in very high numbers within the corona zone. The overall number of CD20+ B cells was much lower. However, in 6 of 12 patients (50%), at least 1 B cell aggregate was present in the fibrovascular zone. Large numbers of cells expressing interleukin-1, (IL-1,) were observed in the corona zone. Transforming growth factor ,1 (TGF,1),expressing mononucleated cells were also identified. The number of CD68+ cells correlated with the number of cells expressing IL-1, (r = 0.691, P = 0.009) and the number expressing TGF,1 (r = 0.518, P = 0.04). Conclusion The tophus represents a complex and organized chronic inflammatory tissue response to monosodium urate monohydrate crystals involving both innate and adaptive immune cells. The coexpression of IL-1, and TGF,1 suggests that both proinflammatory and antiinflammatory factors present within the tophus contribute to a cycle of chronic inflammation, attempted resolution, and tissue remodeling. [source]

    Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals

    ARTHRITIS & RHEUMATISM, Issue 2 2006
    Yousuke Murakami
    Objective Triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface molecule that was recently identified on monocytes and neutrophils. TREM-1 has been implicated in the early inflammatory responses induced by microbes, but its pathophysiologic role in nonmicrobial inflammation remains unknown. In the present study, we investigated the role of TREM-1 in acute inflammation induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM-1 expression by MSU crystal,stimulated murine resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation was determined. The biologic role of TREM-1 in crystal-induced cytokine production by resident peritoneal macrophages was also investigated. Methods TREM-1 expression by resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model was determined by quantitative real-time polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine production by resident peritoneal macrophages after incubation with MSU crystals in the presence or absence of an anti,TREM-1 agonist antibody was determined by enzyme-linked immunosorbent assay. Results TREM-1 expression by resident peritoneal macrophages was significantly induced after stimulation with the crystals. Maximum expression of TREM-1 transcripts and protein occurred at 1 and 4 hours after exposure to the crystals, respectively. Costimulation of resident peritoneal macrophages with MSU crystals and an anti,TREM-1 agonist antibody synergistically increased the production of both interleukin-1, and monocyte chemotactic protein 1 compared with stimulation with the crystals alone. MSU crystals also induced TREM-1 expression in infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation. Conclusion These findings suggest that rapid induction of TREM-1 expression on resident peritoneal macrophages and neutrophils by MSU crystals may contribute to the development of acute gout through enhancement of inflammatory responses. [source]

    Rapid induction of peroxisome proliferator,activated receptor , expression in human monocytes by monosodium urate monohydrate crystals

    ARTHRITIS & RHEUMATISM, Issue 1 2003
    Tohru Akahoshi
    Objective Peroxisome proliferator,activated receptor , (PPAR,) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPAR, in self-limiting episodes of acute gouty arthritis. To do this, we investigated PPAR, expression by monosodium urate monohydrate (MSU) crystal,stimulated monocytes, and we studied the effects of PPAR, ligands on crystal-induced acute inflammation. Methods PPAR, expression by MSU crystal,stimulated human peripheral blood mononuclear cells was determined by reverse transcription,polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPAR, ligands on in vitro crystal-induced cytokine production and on in vivo cellular infiltration during crystal-induced acute inflammation were also investigated. Results MSU crystals rapidly and selectively induced PPAR, expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPAR, was functional, since a PPAR, ligand was able to up-regulate CD36 expression on monocytes. A natural ligand of PPAR,, 15-deoxy-,12,14 -prostaglandin J2 (15deoxy-PGJ2), significantly reduced the crystal-induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy-PGJ2 significantly prevented cellular accumulation in a mouse air-pouch model of MSU crystal,induced acute inflammation. Conclusion Rapid induction of PPAR, expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout. [source]