NEW MECHANISM FOR GLOMERULAR INJURY - MYELOPEROXIDASE-HYDROGEN PEROXIDE-HALIDE SYSTEM
NEW MECHANISM FOR GLOMERULAR INJURY - MYELOPEROXIDASE-HYDROGEN PEROXIDE-HALIDE SYSTEM
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DOI：
10.1172/jci112965
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发表时间：
1987-05-01
影响因子：
15.9
通讯作者：
KLEBANOFF, SJ
中科院分区：
文献类型：
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作者：
JOHNSON, RJ;COUSER, WG;KLEBANOFF, SJ
活性氧，特别是过氧化氢（H2O2），参与中性粒细胞介导的肾小球肾炎。然而，H2O2的肾毒性机制尚不清楚。髓过氧化物酶（MPO）是一种定位于肾小球的中性粒细胞阳离子酶，可与H2O2和卤化物反应形成高活性产物。我们通过向大鼠肾动脉灌注含氯溶液的MPO和H2O2，验证了MPO-H2O2-卤化物系统诱导肾小球损伤的假设。对照组单独接受MPO或H2O2。mpo - h2o2灌注大鼠出现明显的蛋白尿、内皮细胞肿胀和上皮细胞足突消退，而对照组肾脏正常。在游离125I存在的情况下，mpo - h2o2灌注大鼠将大量125I通过放射自显像定位于肾小球基底膜和系膜进入肾小球。对照组肾小球碘含量明显降低或不存在。mpo - h2o2 -卤化物系统引起肾小球损伤，可能在中性粒细胞介导的肾小球肾炎中起重要作用。
Reactive oxygen species, particularly hydrogen peroxide (H2O2), participate in neutrophil-mediated glomerulonephritis. However, the mechanism of H2O2 neptrotoxicity is unknown. Myeloperoxidase (MPO), a neutrophil cationic enzyme that localizes in glomeruli, can react with H2O2 and halides to form higly reactive products. We tested the hypothesis that the MPO-H2O2-halide system may induce glomerular injury by infusing MPO followed by H2O2 in a chloride-containing solution into the renal artery of rats. Controls received MPO or H2O2 alone. MPO-H2O2-perfused rat developed significant proteinuria, endothelial cell swelling, and epithelial cell foot process effacement, whereas control kidneys were normal. In the presence of free 125I, MPO-H2O2-perfused rats incorporated large amounts of 125I, localized to the glomerular basement membrane and mesangium by autoradiography, into glomeruli. Glomerular iodination was greatly decreased or absent in controls. The MPO-H2O2-halide system causes glomerular injury and may be important in neutrophil-mediated glomerulonephritis.