体外诱导肥大细胞活化对类风湿性滑膜组织前列腺素E和金属蛋白酶产生的影响。
Effects of induced mast cell activation on prostaglandin E and metalloproteinase production by rheumatoid synovial tissue in vitro.
作者信息
Tetlow L C, Harper N, Dunningham T, Morris M A, Bertfield H, Woolley D E
机构信息
University Department of Medicine, Manchester Royal Infirmary.
出版信息
Ann Rheum Dis. 1998 Jan;57(1):25-32. doi: 10.1136/ard.57.1.25.
OBJECTIVE
To determine whether induced mast cell activation/degranulation in rheumatoid synovial explants modulates the production of prostaglandin E (PGE2), and the matrix metalloproteinases (MMPs) collagenase 1, gelatinase A, and stromelysin 1.
METHODS
Synovial explant cultures were treated either with rabbit IgG anti-human IgE as a mast cell (MC) secretagogue or with non-immune rabbit IgG as controls. After 20 hours conditioned medium was assayed for the release of MC tryptase, PGE2, collagenase 1, gelatinase A, and stromelysin 1 using radioimmunoassay, enzyme linked immunosorbent assay, western blot, and zymogram techniques; tissue explants were examined immunohistologically for the relative distributions of MC tryptase, collagenase 1, and stromelysin 1.
RESULTS
Over a 20 hour incubation period the MC secretagogue treated explants showed a significant increase in the quantities of released tryptase and PGE2 compared with controls. By contrast, the three MMPs showed variable values between experiments in response to MC activation; no reproducible trend of either an increased or decreased production of each MMP over control values was evident. Each MMP initially appeared as an inactive precursor form; collagenase 1 and stromelysin 1 were more effectively processed to active forms in the MC activated cultures. Immunolocalisation studies of MC activated explants showed that areas of extracellular tryptase were commonly associated with the local production of both collagenase 1 and stromelysin 1.
CONCLUSION
MC degranulation induced artificially in rheumatoid synovial explant cultures consistently resulted in an increased production of PGE2 but had variable effects on the quantification of released collagenase 1, gelatinase A, and stromelysin 1. Such observations support the concept that activated synovial MCs within their native environment stimulate the production of non-MC derived PGE2 and may contribute to the regulation and processing of specific MMPs; both aspects represent important components of the inflammatory and degradative processes of the rheumatoid lesion.
目的
确定类风湿性滑膜外植体中诱导的肥大细胞活化/脱颗粒是否会调节前列腺素E（PGE2）以及基质金属蛋白酶（MMPs）胶原酶1、明胶酶A和基质溶解素1的产生。
方法
滑膜外植体培养物分别用兔抗人IgE IgG作为肥大细胞（MC）促分泌剂处理，或用非免疫兔IgG作为对照。20小时后，使用放射免疫测定、酶联免疫吸附测定、蛋白质印迹和酶谱技术检测条件培养基中MC类胰蛋白酶、PGE2、胶原酶1、明胶酶A和基质溶解素1的释放；对外植体组织进行免疫组织学检查，以确定MC类胰蛋白酶、胶原酶1和基质溶解素1的相对分布。
结果
在20小时的孵育期内，与对照组相比，经MC促分泌剂处理的外植体释放的类胰蛋白酶和PGE2量显著增加。相比之下，三种MMPs在不同实验中对MC活化的反应值各不相同；与对照值相比，每种MMP的产生没有明显的增加或减少的可重复趋势。每种MMP最初均以无活性的前体形式出现；在MC活化培养物中，胶原酶1和基质溶解素1更有效地加工成活性形式。对MC活化外植体的免疫定位研究表明，细胞外类胰蛋白酶区域通常与胶原酶1和基质溶解素1的局部产生相关。
结论
在类风湿性滑膜外植体培养物中人工诱导的MC脱颗粒始终导致PGE2产生增加，但对释放的胶原酶1、明胶酶A和基质溶解素1的定量有不同影响。这些观察结果支持这样的概念，即天然环境中活化的滑膜MC刺激非MC来源的PGE2产生，并可能有助于特定MMPs的调节和加工；这两个方面都是类风湿性病变炎症和降解过程的重要组成部分。
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