Impaired activity of protease inhibitors towards neutrophil elastase bound to human articular cartilage
Impaired activity of protease inhibitors towards neutrophil elastase bound to human articular cartilage
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DOI：
10.1136/ard.55.4.248
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发表时间：
1996-04-01
影响因子：
27.4
通讯作者：
Willoughby, DA
中科院分区：
文献类型：
--
作者：
Kawabata, K;Moore, AR;Willoughby, DA
目的研究蛋白酶抑制剂对中性粒细胞弹性蛋白酶和软骨结合型弹性蛋白酶体外降解软骨蛋白多糖能力的影响。结果-高分子量蛋白酶抑制剂（α（1）蛋白酶抑制剂，α（2）巨球蛋白，和大豆胰蛋白酶抑制剂）和类风湿性关节炎患者的滑液有效地阻断了用游离弹性蛋白酶处理的切片的蛋白聚糖损失，但是它们对软骨结合的弹性蛋白酶的活性大大降低。与此相反，低分子量弹性蛋白酶抑制剂（N-甲氧基琥珀酰-丙氨酸-丙氨酸-脯氨酸-Val氯甲基酮和ONO-5046（N-[2-[4-（2，2-二甲基丙酰氧基）苯基磺酰氨基]苯甲酰基]氨基乙酸）是有效的对自由和软骨结合的弹性蛋白酶。结论-弹性蛋白酶的结合软骨似乎是一种机制，使酶可以保持活性的存在下，高分子量蛋白酶抑制剂。
Objective-To investigate the effects of protease inhibitors on the ability of free and cartilage bound neutrophil elastase to degrade cartilage proteoglycan in vitro.Methods-Cryostat sections of human articular cartilage were used as substrate, and proteoglycan loss induced by free or cartilage bound elastase was quantified by alcian blue staining, followed by scanning and integrating microdensitometry.Results-High molecular mass protease inhibitors (alpha(1) protease inhibitor, alpha(2) macroglobulin, and soya bean trypsin inhibitor) and synovial fluid from patients with rheumatoid arthritis were effective in blocking proteoglycan loss from sections treated with free elastase, but their activity towards cartilage bound elastase was much reduced. In contrast, low molecular mass elastase inhibitors (N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethylketone and ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulphonylamino]benzoyl] amino-acetic acid) were effective against free and cartilage bound elastase.Conclusion-The binding of elastase to cartilage appears to be a mechanism whereby the enzyme can remain active in the presence of high molecular mass protease inhibitors.