Disease relevance of uric acid

• Studies in vitro established these "beachball" structures as chemically identical to classic "needles" of monosodium urate monohydrate, the prime factor in gouty arthritis [1].
• In this study, we show that the inflammatory microcrystals monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD), the major mediators of gout and pseudogout, differentially regulate the production of these two chemokines by human neutrophils [2].
• Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersaturation of urine with respect to monosodium urate [3].
• Central role of complement membrane attack complex in monosodium urate crystal-induced neutrophilic rabbit knee synovitis [4].
• METHODS: We studied MSU crystal-induced peritonitis in TG2(-/-) and congenic TG2(+/+) mice [5].

High impact information on uric acid

• Both MSU and CPPD increased the secretion of IL-8 by neutrophils in a dose- and time-dependent manner, but had no effect on that of MIP-1 alpha [2].
• These LPS did not enhance platelet stimulation by antiplatelet antibody, monosodium urate crystals, or thrombin and only slightly enhanced stimulation by insoluble human skin collagen [6].
• These findings prompt questions concerning how the innate immune system recognizes MSU and the identities of the receptors involved [7].
• Overall, these results demonstrate that colchicine specifically and significantly inhibits the protein tyrosine phosphorylation induced by MSU and CPPD crystals and suggest that its effects are associated, at least in part, with its interaction with microtubules [8].
• Factors that modulate the ability of monosodium urate crystals to stimulate leukocytes could regulate gouty inflammation [9].

Chemical compound and disease context of uric acid

• Mechanism of neutrophil activation by an unopsonized inflammatory particulate. Monosodium urate crystals induce pertussis toxin-insensitive hydrolysis of phosphatidylinositol 4,5-bisphosphate [10].
• Studies during the Gemini, Apollo, Skylab and Shuttle missions demonstrated alterations in renal function, fluid homeostasis and bone resorption that result in increased urinary supersaturation of calcium oxalate, brushite, sodium urate and uric acid [11].
• We stress the importance of fixation of biopsy material in formalin and alcohol to avoid diagnostic errors, since granuloma with histologic features resembling a rheumatoid nodule or rheumatoid synovitis may show the presence of crystals of monosodium urate when examined with compensated polarized light microscopy [12].
• Both IL1 beta protein and mRNA were measured following cell activation with bacterial endotoxin (lipopolysaccharide; LPS), and pro-inflammatory crystals of monosodium urate (MSU), which cause arthritis and kidney disease [13].
• SK&F 105809 inhibited oedema and inflammatory-cell infiltration in arachidonic acid-induced inflammation in the mouse ear and rat paw as well as in carrageenan- and monosodium urate crystal-induced peritonitis [14].

Biological context of uric acid

• Immunoglobulin G independent activation of the classical complement pathway by monosodium urate crystals [15].
• To facilitate our studies on the mechanisms controlling collagenase production at a molecular level in rabbit synovial fibroblasts, we have constructed a cDNA library using mRNAs isolated from cells induced with crystals of monosodium urate monohydrate [16].
• Noninflammatory phagocytosis of monosodium urate monohydrate crystals by mouse macrophages. Implications for the control of joint inflammation in gout [17].
• The effects of monosodium urate and calcium pyrophosphate dihydrate crystals on the levels of cytoplasmic free calcium and on the oxidative burst in normal human blood neutrophils were examined [18].
• Plasma protein binding by monosodium urate crystals. Analysis by two-dimensional gel electrophoresis [19].

Anatomical context of uric acid

• Crystals of monosodium urate (MSU) provide a dose-dependent stimulus for the production by human blood monocytes of tumor necrosis factor (TNF), a cytokine with proinflammatory properties; TNF activity was inhibited selectively by monoclonal antibody to TNF alpha [20].
• It shows promise in biological (clinical) specimens also, as demonstrated here in studies of synovial fluid, synovium, and gouty tophus, selected for their known content of sodium urate and calcium pyrophosphate crystals [21].
• MEASUREMENTS: Frequency with which arthrocentesis yielded synovial fluid; presence of monosodium urate crystals in the synovial fluid sample; and, for synovial fluid with crystals, the number of microscope fields that had to be scanned before crystals were found [22].
• Tyrosine phosphorylation responses to MSU crystals develop during the Me2SO4-induced differentiation of HL-60 cells in parallel with the surface expression of CD16 [23].
• Monosodium urate crystals in the knee joints of patients with asymptomatic nontophaceous gout [24].

Associations of uric acid with other chemical compounds

• Apolipoprotein (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 [9].
• Starch-heptane extraction depleted greater than 95% of neutral lipids but had little effect on the capacity of LDL to inhibit monosodium urate crystal- or polystyrene latex bead-induced neutrophil chemiluminescence (CL) [25].
• This study was performed to examine the effect of SP-receptor desensitization in two well-established models of tonic (prolonged) nociception: the formalin test and the monosodium urate (MSU) test [26].
• Increased level of translatable collagenase messenger ribonucleic acid in rabbit synovial fibroblasts treated with phorbol myristate acetate or crystals of monosodium urate monohydrate [27].
• Seeds of monosodium urate caused heterogeneous nucleation of calcium oxalate at pH 5.7 and 6.7, and of calcium phosphate at pH 5.3, 5.7, and 6.7 from metastably supersaturated solutions in vitro [28].

Gene context of uric acid

• Monosodium urate microcrystals induce cyclooxygenase-2 in human monocytes [29].
• Interaction of GM-CSF- and TNF-alpha-treated neutrophils with MSU or CPPD up-regulated IL-1 while simultaneously down-regulating IL-1Ra [30].
• Antiinflammatory effect of retrovirally transfected interleukin-10 on monosodium urate monohydrate crystal-induced acute inflammation in murine air pouches [31].
• TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation [32].
• Although they are involved in fMet-Leu-Phe (fMLP)-mediated PLD activation, their role in monosodium urate (MSU)-stimulated PLD1 activity in human neutrophils is not clear [33].

Analytical, diagnostic and therapeutic context of uric acid

• Uptake of 1.2B6 in inflamed and control joints was assessed by scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals [34].
• Evidence for a role for SAM68 in the responses of human neutrophils to ligation of CD32 and to monosodium urate crystals [35].
• Previously, we showed that hyperuricosuria, simulated by the addition of dissolved sodium urate, promotes the crystallization of CaOx [36].
• Arthritis induced in cat by sodium urate: a possible animal model for tonic pain [37].
• Response to intradermal injection of monosodium urate crystals in Behçet's syndrome [38].

References