SYNOVIAL PROCOLLAGENASE ACTIVATION BY HUMAN MAST-CELL TRYPTASE DEPENDENCE UPON MATRIX METALLOPROTEINASE-3 ACTIVATION
SYNOVIAL PROCOLLAGENASE ACTIVATION BY HUMAN MAST-CELL TRYPTASE DEPENDENCE UPON MATRIX METALLOPROTEINASE-3 ACTIVATION
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DOI：
10.1172/jci114344
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发表时间：
1989-11-01
影响因子：
15.9
通讯作者：
RAMAMURTHY, NS
中科院分区：
文献类型：
--
作者：
GRUBER, BL;MARCHESE, MJ;RAMAMURTHY, NS
肥大细胞与类风湿关节软骨和骨质结构中观察到的基质降解的发病机制有关。我们以前报道，人肥大细胞类胰蛋白酶，134-kD的颗粒相关的中性蛋白酶，存在于类风湿滑膜，并能激活胶原酶在粗培养液在体外。本研究试图描述这种激活的确切机制。类胰蛋白酶可激活基质金属蛋白酶3（MMP-3）或基质溶解素（stromelysin），并呈时间和剂量依赖性。在通过免疫吸附去除proMMP-3的培养类风湿性滑膜细胞的粗培养基中，Typtase不能产生活性胶原酶。此外，金属蛋白酶组织抑制剂（TIMP）的功能不被类胰蛋白酶改变，SDS-PAGE分析显示TIMP不被类胰蛋白酶降解。类胰蛋白酶依赖的滑膜细胞前胶原酶的激活因此似乎完全依赖于其激活proMMP-3的能力。
Mast cells have been implicated in the pathogenesis of the matrix degradation observed in the cartilaginous and osseous structures of the rheumatoid joint. We previously reported that human mast cell tryptase, a 134-kD granule-associated neutral protease, is present in rheumatoid synovium and can activate collagenase in crude culture medium in vitro. The present study attempts to depict the precise mechanism of this activation. To express full activation of latent collagenase, matrix metalloproteinase 3 (MMP-3) or stromelysin, can be activated by tryptase in a time and dose-dependent manner. Typtase was not capable of generating active collagenase in the crude media from cultured rheumatoid synoviocytes depleted of proMMP-3 by immunoadsorption. In addition, the function of the tissue inhibitor of metalloproteinases (TIMP) was not altered by tryptase, and SDS-PAGE analysis revealed no degradation of TIMP by tryptase. The tryptase dependent activation of synoviocyte procollagenase thereby appears to be entirely dependent upon its ability to activate proMMP-3.