Shirakata Y, Kobayashi M, Ohtsuka K, Sugano M, Terajima H, Ikai I, Okajima H, Egawa H, Inomata Y, Inamoto T
Second Department of Surgery, Faculty of Medicine, College of Medical Technology, Kyoto University, Japan.
Transplantation. 1995 Dec 27;60(12):1582-7. doi: 10.1097/00007890-199560120-00035.
To evaluate the roles of extracellular FKBP12, we examined the effect of extracellular FKBP12 on the immunosuppressive activity of FK506 in vitro and clinically. The ability of FK506 to suppress phytohemagglutinin-induced proliferative response of human peripheral blood mononuclear cells was inhibited in the presence of recombinant FKBP12 dose-dependently. We measured plasma levels of FKBP12 using a newly developed enzyme-linked immunosorbent assay system in 34 patients receiving FK506 after liver transplantation. In 7 patients with acute cellular rejection, plasma FKBP12 increased significantly at the onset of rejection compared with 1 week before onset (P < 0.05) and further increased to or remained at more than 250 ng/ml 1 week after onset. In 22 of 27 patients without acute cellular rejection, plasma FKBP12 was less than 70 ng/ml during the 4 weeks after transplantation. In the other 5 of 27 patients without acute cellular rejection, plasma FKBP12 exceeded 250 ng/ml. Rapid increase of plasma FKBP12 was observed in only one of these 5 patients, at the onset of high fever due to a liver abscess. There was no significant difference in whole blood trough levels of FK506 between the patients with or without acute cellular rejection. These results suggest that the rapid increase in plasma levels of FKBP12 may contribute to the occurrence and progress of acute cellular rejection probably by inhibiting the immunosuppressive activity of FK506.
为了评估细胞外FKBP12的作用，我们在体外和临床研究了细胞外FKBP12对FK506免疫抑制活性的影响。在重组FKBP12存在的情况下，FK506抑制人外周血单个核细胞的植物血凝素诱导的增殖反应的能力呈剂量依赖性受到抑制。我们使用新开发的酶联免疫吸附测定系统测量了34例肝移植后接受FK506治疗的患者血浆中FKBP12的水平。在7例急性细胞排斥反应患者中，与排斥反应发作前1周相比，排斥反应发作时血浆FKBP12显著升高（P<0.05），发作后1周进一步升高至或保持在250 ng/ml以上。在27例无急性细胞排斥反应的患者中，22例在移植后4周内血浆FKBP12低于70 ng/ml。在27例无急性细胞排斥反应的其他5例患者中，血浆FKBP12超过250 ng/ml。在这5例患者中，只有1例在因肝脓肿高热发作时观察到血浆FKBP12迅速升高。有或无急性细胞排斥反应的患者之间FK506的全血谷浓度无显著差异。这些结果表明，血浆FKBP12水平的迅速升高可能通过抑制FK506的免疫抑制活性而有助于急性细胞排斥反应的发生和进展。
