Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eicosanoids are important mediators of the inflammatory response to monosodium urate crystals (MSUC) that results in gout. Phospholipase enzymes cleave fatty acids from membrane phospholipids, and this is thought to be the rate-limiting step in eicosanoid production. To understand better the mechanism of eicosanoid production in this disease, we stimulated human peripheral blood neutrophils and monocytes with MSUC and measured phospholipase enzyme activities. MSUC stimulated both intracellular and secretory phospholipase A2 enzyme activities in a time and concentration-dependent manner. Specificity was observed, as phospholipase C activities were not affected. Pretreatment with colchicine, but not aspirin, indomethacin, allopurinol, or islet activating protein, abrogated the enhanced phospholipase A2 activities. We have recently isolated and characterized a phospholipase A2 activating protein termed PLAP from synovial fluid from patients with rheumatoid arthritis, and from murine and bovine cell lines. PLAP was detected in gouty synovial fluid by immunodot blotting and ELISA assays and expressed the same characteristics as PLAP identified from other sources. To examine the role of PLAP in MSUC-induced phospholipase A2 stimulation, we treated cells with MSUC and observed an increase in immunoreactive PLAP. This response also could be blunted by colchicine, but not other drugs. Both phospholipase A2 and PLAP induced production by human monocytes of PGE2 and leukotriene B4 by neutrophils. These findings suggest that phospholipase A2 activation in response to MSUC requires an intact microtubule structure, and that phospholipase A2 and PLAP may be important modulators of at least a portion of the gouty inflammatory response.
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PMID:Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein. 223 Jan 25

The recognition of tissue deposits of crystalline material in a variety of organs, including the kidney, predated the association of crystals and arthritic disease. Because of this, the pathophysiology of crystal formation and its resultant inflammation is based in part on studies of renal stones. A number of disease states involving renal and articular crystallization exist. The most common of these, uric acid precipitation, or gout, and calcium phosphate precipitation were not reviewed in this discussion. This review described a variety of less common disease states involving articular and renal crystal deposition. The renal diseases discussed included both parenchymal or ectopic crystal deposition, as seen in nephrocalcinosis or cystinosis, and ductal crystallization as seen in renal calculus disease. The crystals involved included not only calcium oxalate, but also aluminum, amino acids and proteins (cystine, hemoglobin, cryoglobulins, and immunoglobulins), purine metabolites (xanthine, hypoxanthine), and even lipids and their degradative enzymes (cholesterol, phospholipids, phospholipase, and fatty acids). The simultaneous occurrence of crystals in both kidneys and joints was found in some cases to result from the systemic deposition of an excess of a particular biological compound. However, of more interest, some renal deposits were shown to more selectively reflect the normal or abnormal function of the kidney in its secretory and excretory roles. This is particularly evident in the variety of arthritic states described in end-stage renal disease.
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PMID:Calcium oxalate and other crystals associated with kidney diseases and arthritis. 264 79