Xanthine oxidoreductase is present in human synovium.

Abstract

SUMMARY It is postulated that the mobile inflamed joint may be subject to cyclical ischaemic reperfusion injury. Xanthine oxidoreductase is an enzyme thought to contribute to oxidative reperfusion injury, and the detection of this activity in human synovium is described. Three normal and five rheumatoid tissues were assayed with a carbon-14 radioassay detecting the conversion of [14C]xanthine to [14C]uric acid. Rheumatoid synovia contained 067-305 ,uU/g tissue (n=5), while normal synovia contained 1-2-5-0 ,uU/g tissue (n=3).Key words: reperfusion, ischaemia, ischaemic reperfusion, xanthine oxidase, xanthine, rheumatoid arthritis.We have previously suggested a mechanism involving ischaemic reperfusion injury to account for the unusual persistence of synovial inflammation.' This involved synovial ischaemia induced by exercise and reperfusion injury occurring on resting. In resting inflamed joints with an effusion, intra-articular pressures are raised compared with those of normal joints, but during exercise the pressure in these joints increases further.2 Lund-Olsen showed that partial pressures of oxygen (Po2) in the synovial fluid are lower in rheumatoid joints than in osteoarthritic or traumatised joints and fall during exercise.3 It is probable that, as the pressures measured during exercise often exceed the capillary perfusion pressure and indeed are greater than systolic blood pressure,24 occlusion of the vessels supplying the synovium occurs, explaining the drop in synovial fluid Po2. Once exercise has ceased intra-articular pressures drop and Po2 levels rise, often above basal levels, consistent, not only with reflow through the synovial vascular bed, but with a reactive hyperaemia.In many tissues much of the damage resulting from an ischaemic incident has been attributed to the postischaemic reperfusion phase,5 the ischaemic phase 'priming' the cells for the destructive activity occurring in the reperfusion phase. During temporary ischaemia low oxygen concentrations halt mitochondrial oxidative phosphorylation, and cellu-

The role of human xanthine oxidoreductase (HXOR), anti-HXOR antibodies, and microorganisms in synovial fluid of patients with joint inflammation

“…The level of human xanthine oxidase protein and its activity is significantly high in the synovial fluid of patient with rheumatoid arthritis (90.43 lg/ml, 100.00 nmol min -1 mg -1 ) ( Table 4). The normal level in healthy individual as reported by others [48,49] is 0.16-0.38 mU/g. This may be due to upregulation of the enzyme by characteristically high levels of cytokines and hypoxic nature of rheumatoid synovium.…”

Enhanced intraarticular free radical reactions in adjuvant arthritis rats

“…The development of RA disease is dependent on many factors including ROS at various stages, and these factors involved at each stage would be different. The sources of ROS have been reported as NADPH oxidase [10,11] and xanthine oxidoreductase [12] in various tissues. Generation of zOH is supported with in vitro experiment by detecting stable radical-adducts or hydroxylation products of aromatic compounds in inflamed rheumatoid synovium [9].…”

“…By detecting the hydroxylation of aromatic compounds, Kaur et al [9] demonstrated the generation of hydroxyl radical (zOH) in aspirated knee joint fluids and blood from RA patients. Although a source of ROS such as NADPH oxidase [10,11], xanthine oxidoreductase [12], and cyclooxygenase-2 [13,14] have been reported in various tissues, the time-course and the contribution of ROS generation to RA still remains unclear. However, in in vivo, many factors seem to influence the degree of arthritis diseases.…”

Immunohistochemical Localization of Xanthine Oxidase in Human Tissues.

“…According to these studies, xanthine oxidase is localized in epithelial cells of kidney, intestine, and mammary gland, goblet cells, pancreatic acinar cells, and skeletal muscle cells, as well as in endothelial cells from various organs and liver cells. However, immunohistochemical localization of xanthine oxidase in human tissues has not been extensively examined, except for a few studies on a limited number of tissues [1,5,9,19,25]. We determined the immunohistochemical localization of xanthine oxidase in various human tissues.…”