Newcom S R, Kadin M E, Ansari A A, Diehl V
Department of Medicine, Emory University, Atlanta, Georgia 30322.
J Clin Invest. 1988 Dec;82(6):1915-21. doi: 10.1172/JCI113810.
Nodular sclerosing Hodgkin's disease is characterized by dense collagen fibrosis. Although transforming growth factor-beta (TGF-beta) is an important bifunctional growth factor for fibroblasts and is stored and released by many cells, it requires acidification to pH 2.0-3.0 before it becomes a biologically active growth factor. We show here that the L-428 Hodgkin's cell releases a high molecular weight TGF that competes for the TGF-beta cell membrane receptor but not the TGF-alpha receptor. This growth factor is most active at physiologic pH and is 97% inactivated by acidification. Hodgkin's TGF is also inactivated by proteases and can be preserved by protease inhibitors. The Hodgkin's TGF can be separated from an autocrine growth factor using either column chromatography or electroelution from gels and is shown to have a molecular weight of approximately 350,000. Incubation of the Hodgkin's TGF in SDS releases a 25,000-D protein with reduced biological activity but which cross-reacts with anti-TGF-beta IgG. We propose that L-428 nodular sclerosing Hodgkin's disease fibrosis is mediated by a potent high molecular weight TGF-beta which, unlike TGF-beta characterized to date, is secreted in a form most active at physiologic pH.
结节硬化型霍奇金淋巴瘤的特征是存在致密的胶原纤维化。尽管转化生长因子-β（TGF-β）是成纤维细胞的一种重要双功能生长因子，且由许多细胞储存和释放，但它在变成生物活性生长因子之前需要酸化至pH 2.0 - 3.0。我们在此表明，L - 428霍奇金细胞释放一种高分子量的TGF，它能与TGF-β细胞膜受体结合竞争，但不能与TGF-α受体竞争。这种生长因子在生理pH时活性最强，酸化会使其97%失活。霍奇金TGF也会被蛋白酶灭活，蛋白酶抑制剂可使其得以保存。霍奇金TGF可用柱色谱法或从凝胶中电洗脱与自分泌生长因子分离，其分子量约为350,000。霍奇金TGF在SDS中孵育会释放出一种生物活性降低但能与抗TGF-β IgG交叉反应的25,000 - D蛋白。我们提出，L - 428结节硬化型霍奇金淋巴瘤的纤维化是由一种强效的高分子量TGF-β介导的，与迄今所描述的TGF-β不同，它以在生理pH时活性最强的形式分泌。
