Destruction of articular cartilage by alpha₂ macroglobulin elastase complexes:: role in rheumatoid arthritis

作     者：Moore, AR Appelboam, A Kawabata, K Da Silva, JAP D'Cruz, D Gowland, G Willoughby, DA 

作者机构：St Bartholomews & Royal London Sch Med & Dent Dept Expt Pathol London EC1M 6BQ England 

出 版 物：《ANNALS OF THE RHEUMATIC DISEASES》 (风湿病纪事)

年 卷 期：1999年第58卷第2期

页      面：109-113页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：关节炎 类风湿/代谢 软骨 关节/代谢 色谱法 色谱法 凝胶 膝关节 白细胞弹性蛋白酶/拮抗剂和抑制剂 白细胞弹性蛋白酶/代谢 蛋白质结合 蛋白聚糖类/代谢 滑液/酶学 滑液/代谢 α1抗胰蛋白酶/代谢 α巨球蛋白类/代谢 成年人 人类 

摘      要：Objective-Neutrophil elastase accounts for the ability of some fresh rheumatoid synovial fluids to degrade cartilage matrix in vitro. The aim of this study was to determine if enzyme activity could result from depletion of synovial fluid inhibitors or protection of the enzyme from inhibition. Methods-The ability of synovial fluids to inhibit porcine pancreatic elastase was investigated together with chemical pretreatments capable of inactivating alpha, protease inhibitor (alpha(1)PI) or preventing formation of alpha, macroglobulin (alpha(2)M) elastase complexes. Subsequently, complexes of human neutrophil elastase with alpha(2)M were prepared and applied to frozen sections of cartilage. Proteoglycan loss was quantified by alcian blue staining and scanning and integrating microdensitometry. Parallel studies were carried out using a low molecular weight chromogenic elastase substrate. The effects of alpha(1)PI and SF on these systems were investigated. Finally, synovial fluids were subjected to gel filtration and the fractions assayed for elastase activity. High molecular weight fractions were pooled, concentrated, and tested for their ability to degrade cartilage sections. Results-All synovial fluids reduced the activity of porcine pancreatic elastase, the inhibition mainly being attributable to alpha(1)PI, whereas remaining activity resulted from complexes of elastase with alpha(2)M. Complexes of human neutrophil elastase with alpha(2)M were shown to cause proteoglycan degradation in frozen sections of human articular cartilage. Alpha(1)PI prevented alpha(2)M elastase complexes from degrading cartilage but not the chromogenic substrate. The data suggested that alpha(1)PI does not inhibit elastase bound to alpha(2)M but sterically hinders the complex. However, only one of five synovial fluids was able to completely block the actions of alpha(2)M elastase complexes against cartilage. Gel filtration of rheumatoid synovial fluids showed elastase and cartilage degrading