Kammer G M, Sapolsky A I, Malemud C J
J Clin Invest. 1985 Aug;76(2):395-402. doi: 10.1172/JCI111985.
Destruction of articular cartilage is the hallmark of inflammatory arthritides. Enzymes elaborated by mononuclear cells infiltrating the synovium mediate, in part, the degradation of the cartilage extracellular matrix. Since mononuclear cells are the dominant cell type found in chronic inflammatory synovitis, we investigated whether interaction of immune mononuclear cells with antigen initiated the synthesis and secretion of a proteoglycan-degrading enzyme activity. Proteoglycan-degrading enzyme activity was monitored by the capacity of murine spleen cell conditioned medium to release [3H]serine/35SO4 incorporated into rabbit cartilage proteoglycan monomer fraction (A1D1), and by the relative change in specific viscosity of bovine nasal cartilage proteoglycan monomer. The results demonstrated that both virgin and immune mononuclear cells spontaneously generated proteoglycan-degrading enzyme activity and that cellular activation and proliferation induced by the antigen keyhole limpet hemocyanin or the mitogen phytohemagglutinin was not required. Kinetic studies demonstrated stable release of the enzyme activity over 72 h. Cell separation studies showed that T lymphocytes, a thymoma line, and macrophages separately produced proteoglycan-degrading enzyme activity. The enzyme activity has been partially characterized and appears to belong to a class of neutral pH metal-dependent proteinases. These observations, the first to demonstrate that T lymphocytes secrete an enzyme capable of degrading cartilage proteoglycan, raise the possibility that this enzyme activity contributes to cartilage extracellular matrix destruction in vivo. Moreover, these data support the conclusion that production of this enzyme by T lymphocytes is independent of an antigen-specific stimulus.
关节软骨破坏是炎性关节炎的标志。浸润滑膜的单核细胞所分泌的酶部分介导了软骨细胞外基质的降解。由于单核细胞是慢性炎症性滑膜炎中发现的主要细胞类型，我们研究了免疫单核细胞与抗原的相互作用是否启动了蛋白聚糖降解酶活性的合成与分泌。通过小鼠脾细胞条件培养基释放掺入兔软骨蛋白聚糖单体部分（A1D1）的[3H]丝氨酸/35SO4的能力以及牛鼻软骨蛋白聚糖单体比粘度的相对变化来监测蛋白聚糖降解酶活性。结果表明，未致敏和免疫单核细胞均可自发产生蛋白聚糖降解酶活性，且不需要由抗原钥孔血蓝蛋白或促细胞分裂剂植物血凝素诱导的细胞活化和增殖。动力学研究表明，酶活性在72小时内稳定释放。细胞分离研究表明，T淋巴细胞、一种胸腺瘤系和巨噬细胞分别产生蛋白聚糖降解酶活性。该酶活性已得到部分表征，似乎属于一类中性pH值金属依赖性蛋白酶。这些首次证明T淋巴细胞分泌一种能够降解软骨蛋白聚糖的酶的观察结果，增加了这种酶活性在体内促成软骨细胞外基质破坏的可能性。此外，这些数据支持T淋巴细胞产生这种酶独立于抗原特异性刺激的结论。
