Endogenous activation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator.
Endogenous activation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator.
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类风湿滑膜细胞对潜在胶原酶的内源性激活。
DOI：
10.1056/nejm197705052961801
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发表时间：
1977
期刊：
影响因子：
--
通讯作者：
E. D. Harris
中科院分区：
文献类型：
--
作者：
Z. Werb;C. Mainardi;C. Vater;E. D. Harris
为了阐明类风湿关节炎滑膜损伤的机制，我们研究了培养物中贴壁类风湿滑膜细胞释放的潜在胶原酶的激活。潜伏酶不与血清中主要蛋白酶抑制剂α2巨球蛋白复合，并且如果向饱和抑制剂中添加足够的蛋白酶，则在α2巨球蛋白存在的情况下可以被胰蛋白酶激活。潜在胶原酶与胶原原纤维的结合效率只有活性酶的一半。纤溶酶是比胰蛋白酶更好三倍的潜在酶激活剂，并且可以通过向滑膜细胞培养物中添加纤溶酶原来产生。地塞米松(10(-9)M)抑制胶原酶和纤溶酶原激活剂的产生。这些研究强调了控制激活在调节胶原酶活性中的重要性。类风湿滑膜很可能产生潜在的胶原酶和纤溶酶原激活剂；纤溶酶由存在于发炎组织中的酶原纤溶酶原激活，进而激活胶原酶。
To elucidate the mechanism of synovial damage in rheumatoid arthritis, we studied the activation of latent collagenases released from adherent rheumatoid synovial cells in culture. Latent enzyme was not complexed with alpha2 macroglobulin, the prinicpal proteinase inhibitor in serum, and could be activated by trypsin in the presence of alpha2 macroglobulin if sufficient proteinase was added to saturate inhibitor. Latent collagenase bound half as effectively to collagen fibrils as active enzyme. Plasmin was a threefold better activator of latent enzyme than trypsin and could be generated by addition of plasminogen to synovial-cell cultures. Production of both collagenase and plasminogen activator was inhibited by dexamethasone (10(-9) M). These studies emphasize in importance of control of activation in regulation collagenase activity, It is likely that rheumatoid synovium produces both latent collagenase and plasminogen activator; plasmin is activated from its zymogen, plasminogen, present in inflamed tissues, and in turn activates collagenase.