Carlesen E, Prydz H
Transplantation. 1987 Apr;43(4):543-8. doi: 10.1097/00007890-198704000-00018.
At present cyclosporine is the immunosuppressive agent of choice. Although its introduction has led to an improvement in graft and patient survival, an increase in thromboembolic complications has been reported. We have shown previously that exposure to CsA of TPA- and PHA-stimulated monocyte and mononuclear blood cell cultures increased their cellular thromboplastin activity significantly. In this article we report that CsA enhances the synthesis and release of factor VII, as well as the release of thromboplastin, from LPS- and PHA-stimulated monocytes and whole mononuclear cell cultures. The increase in activity of both factors requires de novo protein synthesis. The synthesis and release of thromboplastin and factor VII from the same cells allow efficient formation of their stoichiometric complex, the most potent trigger of blood coagulation known. The enhancement of their synthesis and release by CsA is therefore potentially very important in the pathogenesis of thromboembolic complications.
目前，环孢素是首选的免疫抑制剂。尽管它的应用提高了移植物和患者的存活率，但据报道血栓栓塞并发症有所增加。我们之前已经表明，在TPA和PHA刺激的单核细胞及单核血细胞培养物中暴露于环孢素会显著增加其细胞凝血活酶活性。在本文中，我们报告环孢素可增强脂多糖和PHA刺激的单核细胞及全单核细胞培养物中因子VII的合成与释放，以及凝血活酶的释放。这两种因子活性的增加都需要从头合成蛋白质。同一细胞中凝血活酶和因子VII的合成与释放能够有效形成它们的化学计量复合物，这是已知的最有效的凝血触发因素。因此，环孢素对它们合成与释放的增强在血栓栓塞并发症的发病机制中可能非常重要。
