Eguchi K, Migita K, Nakashima M, Ida H, Terada K, Sakai M, Kawakami A, Aoyagi T, Ishimaru T, Nagataki S
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
J Rheumatol. 1992 Dec;19(12):1925-32.
We demonstrated that vascular endothelial cells mechanically wounded by scraping from the substratum were able to release growth promoting factors for synovial cells as well as for endothelial cells. The wounded endothelial cell conditioned medium stimulated the proliferation of synovial cells derived from different human donors dose dependently and induced transit of growth arrested synovial cells (predominant in the G0 and G1 phases), through the S phase and into the G2 and M phases. When the wounded endothelial cell conditioned medium was applied to heparin-sepharose columns, mitogenic activity was eluted with 2.0 M NaCl. The mitogenic activity in wounded endothelial cell conditioned medium, which was heat sensitive, was inhibited by protamine sulfate and a specific mouse monoclonal antibody against basic fibroblast growth factor (bFGF). Our results are evidence that the wounded endothelial cell conditioned medium contained growth promoting factors for synovial cells, including bFGF. We also showed the presence of bFGF in the endothelial cells of the small blood vessels and stromal synovial fibroblast-like cells in patients with rheumatoid arthritis (RA). Our results suggest that the endothelial cells in the luxuriant capillaries in the synovial tissues from patients with RA may have a critical role in the stimulation of neighboring synovial cell proliferation, resulting in pronounced synovial hyperplasia.
我们证明，从基质上刮擦造成机械损伤的血管内皮细胞能够释放促进滑膜细胞以及内皮细胞生长的因子。损伤的内皮细胞条件培养基剂量依赖性地刺激来自不同人类供体的滑膜细胞增殖，并诱导生长停滞的滑膜细胞（主要处于G0和G1期）通过S期进入G2和M期。当将损伤的内皮细胞条件培养基应用于肝素-琼脂糖柱时，有丝分裂活性在2.0 M NaCl洗脱。损伤的内皮细胞条件培养基中的有丝分裂活性对热敏感，被硫酸鱼精蛋白和抗碱性成纤维细胞生长因子（bFGF）的特异性小鼠单克隆抗体抑制。我们的结果证明，损伤的内皮细胞条件培养基中含有促进滑膜细胞生长的因子，包括bFGF。我们还显示类风湿性关节炎（RA）患者的小血管内皮细胞和滑膜基质成纤维样细胞中存在bFGF。我们的结果表明，RA患者滑膜组织中丰富毛细血管中的内皮细胞可能在刺激邻近滑膜细胞增殖中起关键作用，导致明显的滑膜增生。
