Jasin H E, Dingle J T
J Clin Invest. 1981 Sep;68(3):571-81. doi: 10.1172/jci110290.
Human blood mononuclear cells (BMC) in short-term culture secrete one or more factors that induce degradation of matrix proteoglycan and collagen in cartilage explants in organ culture. Induction of matrix degradation took place both in nasal septum and articular cartilage explants in the presence of the mononuclear cell supernates. Cartilage degradation in this system was absolutely dependent on the presence of live chondrocytes. Matrix depletion did not occur in dead cartilage explants cultured with active supernates. Supernates obtained from unstimulated BMC showed variable cartilage matrix degrading activity (MDA). BMC stimulated with phytohemagglutinin (PHA) showed increased MDA, which in one dilution experiment was found to be five times higher than that in the unstimulated control supernate. Concanavalin A and pokeweed mitogen were also shown to stimulate release of MDA. Time experiments showed that most of the degrading activity was released by the mononuclear cells during the first day of culture. The cellular origin of MDA was investigated with the aid of partially purified BMC subpopulations. Removal of adherent cells resulted in a decrease of MDA release. Purified T lymphocytes failed to show enhanced MDA release in spite of their ability to mount a virtually intact proliferative response to PHA. Purified adherent cells also failed to show enhanced PHA-dependent MDA release. Nevertheless, restoration of PHA-dependent MDA release took place in reconstituted cell populations containing both T lymphocytes and monocytes. These experiments suggest that MDA may be released by adherent mononuclear cells, presumably monocytes, and that the PHA-dependent increase in MDA release may be mediated by T lymphocytes. Partial characterization of MDA by gel chromatography showed one active fraction corresponding to an apparent molecular weight ranging from 12,000 to 20,000. The fraction was also shown to degrade cartilage matrix only in the presence of live chondrocytes. These results demonstrate that factors released by human BMC mediate degradation of matrix proteoglycan and collagen in intact cartilage explants through chondrocyte activation. This pathogenic mechanism may play a role in in vivo cartilage destruction in chronic inflammatory joint diseases.
短期培养的人血单核细胞（BMC）分泌一种或多种因子，可诱导器官培养的软骨外植体中基质蛋白聚糖和胶原蛋白的降解。在单核细胞上清液存在的情况下，鼻中隔和关节软骨外植体中均发生了基质降解的诱导。该系统中的软骨降解绝对依赖于活软骨细胞的存在。用活性上清液培养的死软骨外植体未发生基质消耗。从未经刺激的BMC获得的上清液显示出可变的软骨基质降解活性（MDA）。用植物血凝素（PHA）刺激的BMC显示MDA增加，在一次稀释实验中发现其比未刺激的对照上清液高五倍。还显示刀豆球蛋白A和商陆有丝分裂原可刺激MDA的释放。时间实验表明，大多数降解活性是在培养的第一天由单核细胞释放的。借助部分纯化的BMC亚群研究了MDA的细胞来源。去除贴壁细胞导致MDA释放减少。纯化的T淋巴细胞尽管能够对PHA产生几乎完整的增殖反应，但未显示出MDA释放增强。纯化的贴壁细胞也未显示出PHA依赖性MDA释放增强。然而，在同时含有T淋巴细胞和单核细胞的重组细胞群体中发生了PHA依赖性MDA释放的恢复。这些实验表明，MDA可能由贴壁单核细胞（可能是单核细胞）释放，并且PHA依赖性MDA释放的增加可能由T淋巴细胞介导。通过凝胶色谱对MDA进行部分表征，显示一个活性级分，其表观分子量范围为12,000至20,000。该级分还显示仅在活软骨细胞存在下才降解软骨基质。这些结果表明，人BMC释放的因子通过软骨细胞活化介导完整软骨外植体中基质蛋白聚糖和胶原蛋白的降解。这种致病机制可能在慢性炎症性关节疾病的体内软骨破坏中起作用。
