PRODUCTION OF COLLAGENASE AND TISSUE INHIBITOR OF METALLOPROTEINASES BY FIBROBLASTS DERIVED FROM NORMAL AND FIBROTIC HUMAN LUNGS
PRODUCTION OF COLLAGENASE AND TISSUE INHIBITOR OF METALLOPROTEINASES BY FIBROBLASTS DERIVED FROM NORMAL AND FIBROTIC HUMAN LUNGS
复制标题
DOI：
10.1378/chest.102.4.1085
复制
发表时间：
1992-10-01
期刊：
影响因子：
9.6
通讯作者：
RAGHU, G
中科院分区：
文献类型：
--
作者：
PARDO, A;SELMAN, M;RAGHU, G
一些实验已经证明肺纤维化发展过程中胶原蛋白溶解活性较低。为了确定成纤维细胞是否在这种改变中发挥作用，对来自 12 个人肺样本（正常 = 6，特发性肺纤维化 [IPF] = 6）的成纤维细胞中的原胶原酶和金属蛋白酶组织抑制剂 (TIMP) 进行了定量。在基础条件下，来自正常肺样本的三种细胞株和来自纤维化肺样本的三种细胞株不合成胶原酶，并且相似数量的正常和IPF衍生的成纤维细胞菌株产生该酶。然而，正常和产生纤维化胶原酶的成纤维细胞之间的酶合成速率表现出显着差异。因此，正常成纤维细胞产生超过 300 ng/ml，而纤维化肺成纤维细胞分泌的量约为该量的一半 (115+/-67 ng/ml)。佛波醇肉豆蔻酸酯乙酸酯 (PMA) 增强了所有测试的 12 个肺成纤维细胞系中胶原酶的产生。在四种 IPF 成纤维细胞中，PMA 增加了胶原酶分泌，接近于正常刺激的肺成纤维细胞的分泌；然而，在来自两个纤维化肺样本的细胞株中观察到较低的诱导。正常肺成纤维细胞和纤维化肺成纤维细胞中 TIMP 的产生存在很大差异，并且没有观察到统计学上的显着差异。在基础条件下，正常肺细胞中的 TIMP 水平为 329 至 16,911 ng/ml，纤维化肺成纤维细胞中的 TIMP 水平为 377 至 17,557 ng/ml。 PMA 诱导所有细胞系增加数倍。这些结果表明，肺成纤维细胞亚群具有不同的体外产生胶原酶和 TIMP 的潜力，并且低胶原酶产生亚群的优势可能有助于纤维化的发展。
Several experiments have demonstrated low collagenolytic activity during the development of pulmonary fibrosis. In order to determine if fibroblasts play a role in this alteration, procollagenase and tissue inhibitor of metalloproteinases (TIMP) were quantified in fibroblasts derived from 12 human lung specimens (normal = 6, idiopathic pulmonary fibrosis [IPF] = 6). Under basal conditions, three cell strains from normal and three from fibrotic lung specimens did not synthesize collagenase and a similar number of normal and IPF-derived fibroblast strains produced the enzyme. However, the rate of enzyme synthesis among normal and fibrotic collagenase producing fibroblasts exhibited significant differences. Thus, whereas normal fibroblasts produced more than 300 ng/ml, fibrotic lung fibroblasts secreted approximately half of this amount (115+/-67 ng/ml). Phorbol myristate acetate (PMA) enhanced collagenase production in all of the 12 lung fibroblast lines tested. In four IPF fibroblasts, PMA increased collagenase secretion close to those of normal stimulated lung fibroblasts; however, a lower induction was observed in cell strains from two fibrotic lung specimens. There was a wide variation in TIMP production both in normal and fibrotic lung fibroblasts, and no statistically significant difference was observed. Under basal conditions, TIMP levels ranged from 329 to 16,911 ng/ml in normal lung cells, and from 377 to 17,557 in fibrotic lung fibroblasts. PMA induced a several-fold increase in all cell lines. These results suggest that there are subpopulations of lung fibroblasts with different potential to produce collagenase and TIMP in vitro, and that the predominance of low collagenase-producing subsets may contribute to the development of fibrosis.