Oxidative degradation of rat mast-cell heparin proteoglycan.
Oxidative degradation of rat mast-cell heparin proteoglycan.
复制标题
大鼠肥大细胞肝素蛋白多糖的氧化降解。
DOI：
10.1042/bj2720051
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
HendersonJr,WR
中科院分区：
文献类型：
--
作者：
Metcalfe,DD;Thompson,HL;Klebanoff,SJ;HendersonJr,WR
大鼠肥大细胞肝素氧化降解的敏感性进行了检查。肝素作为完整的肥大细胞颗粒（MCG）的一个组成部分被正常人中性粒细胞摄入后降解。与此相反，慢性肉芽肿病（CGD）患者的中性粒细胞，不响应刺激的爆发活性，表现出大大降低的能力，降解吞噬MCG肝素。MCG相关肝素也被H2 O2加Fe 2+（芬顿试剂）裂解。分离的肝素蛋白聚糖（平均Mr约为750，000）在暴露于芬顿试剂后迅速裂解成与商业猪肝素大小相似的较小分子。过氧化氢酶和羟基自由基（OH.）清除剂甘露醇，而不是由超氧化物歧化酶（SOD）。裂解产物保留约。天然分子的抗凝活性的26%。肝素蛋白聚糖也被乙醛/黄嘌呤氧化酶/FeSO 4切割，这是一种产生超氧化物（O2.-）的系统，H2 O2和OH。而在相对较高的铁离子浓度下的切割抑制过氧化氢酶和甘露醇，但不被SOD，在较低的铁离子浓度下的切割抑制过氧化氢酶，甘露醇和SOD。这些发现表明OH.，其在高Fe 2+浓度下由芬顿试剂（H2 O2加Fe 2+）产生，并且在低铁离子浓度下由铁离子催化的O2. H2 O2（Haber-Weiss反应）。这些研究表明，由活化的吞噬细胞产生的氧自由基可能有助于溶解的和颗粒相关的蛋白聚糖肝素在体内的降解。
The susceptibility of rat mast-cell heparin to oxidative degradation was examined. Heparin as a component of intact mast-cell granules (MCG) was degraded following ingestion by normal human neutrophils. In contrast, neutrophils from patients with chronic granulomatous disease (CGD), which do not respond to stimulation with respiratory-burst activity, exhibited a greatly diminished ability to degrade phagocytosed MCG heparin. MCG-associated heparin also was cleaved by H2O2 plus Fe2+ (Fenton's reagent). Isolated heparin proteoglycan (average Mr approx. 750,000) was rapidly cleaved to smaller molecules similar in size to commercial pig heparin upon exposure to Fenton's reagent. This cleavage was inhibited by catalase and by the hydroxyl-radical (OH.)-scavenger mannitol, but not by superoxide dismutase (SOD). The cleavage products retained approx. 26% of the anticoagulant activity of the native molecule. The heparin proteoglycan was also cleaved by acetaldehyde/xanthine oxidase/FeSO4, a system that generates superoxide (O2.-), H2O2 and OH.. Whereas the cleavage at relatively high iron ion concentrations was inhibited by catalase and mannitol but not by SOD, at lower iron ion concentrations the cleavage was inhibited by catalase, mannitol and SOD. These findings suggest the involvement of OH., which at high Fe2+ concentrations is generated by Fenton's reagent (H2O2 plus Fe2+), and at low iron ion concentrations is generated by the iron-ion-catalysed interaction between O2.- and H2O2 (Haber-Weiss reaction). These studies suggest that oxygen radicals generated by activated phagocytes may contribute to the degradation in vivo of both solubilized and granule-associated proteoglycan heparin.