Slivka S R, Loskutoff D J
Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Blood. 1991 Mar 1;77(5):1013-9.
A model system consisting of thrombin-stimulated bovine platelet releasates (PRthr) and bovine aortic endothelial cells (BAEs) was developed to determine if the interaction between platelets and endothelial cells regulates fibrinolysis. Zymographic analysis indicated that PRthr treatment of BAEs decreases urokinase and increases type 1 plasminogen activator inhibitor (PAI-1) activity. Although PRthr did not affect the overall rate of BAE protein synthesis, it increased PAI-1 biosynthesis within 6 hours. This increase was complete by 12 hours, with maximum stimulation at 10 to 15 micrograms/mL PRthr (1 microgram approximately 10(7) platelets). Neutralizing antibodies to transforming growth factor beta (TGF beta) reduced this effect by 75%. Treatments that activate latent TGF beta (eg, acidification or plasmin) increased this effect approximately fivefold, suggesting that TGF beta in PRthr exists in both a latent (approximately 80%) and an active (approximately 20%) form. In contrast to PRthr, adenosine diphosphate-prepared platelet releasates did not increase PAI-1 synthesis before acidification, indicating that they contain only the latent form of TGF beta. These results suggest that platelets can modulate the fibrinolytic system of the endothelium through the release of TGF beta, and that the mechanism by which the platelets are activated can influence the relative amount of active TGF beta.
建立了一个由凝血酶刺激的牛血小板释放物（PRthr）和牛主动脉内皮细胞（BAE）组成的模型系统，以确定血小板与内皮细胞之间的相互作用是否调节纤维蛋白溶解。酶谱分析表明，用PRthr处理BAE会降低尿激酶并增加1型纤溶酶原激活物抑制剂（PAI-1）的活性。尽管PRthr不影响BAE蛋白质合成的总体速率，但它在6小时内增加了PAI-1的生物合成。这种增加在12小时时完成，在10至15微克/毫升PRthr（1微克约为10^7个血小板）时刺激最大。针对转化生长因子β（TGFβ）的中和抗体使这种作用降低了75%。激活潜伏性TGFβ的处理（如酸化或纤溶酶）使这种作用增加了约五倍，表明PRthr中的TGFβ以潜伏形式（约80%）和活性形式（约20%）同时存在。与PRthr相反，二磷酸腺苷制备的血小板释放物在酸化前不会增加PAI-1的合成，表明它们仅含有潜伏形式的TGFβ。这些结果表明，血小板可以通过释放TGFβ来调节内皮细胞的纤维蛋白溶解系统，并且血小板被激活的机制可以影响活性TGFβ的相对量。
