Horigome A, Hirano T, Oka K, Takeuchi H, Sakurai E, Kozaki K, Matsuno N, Nagao T, Kozaki M
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Immunopharmacology. 1997 Aug;37(1):87-94. doi: 10.1016/s0162-3109(97)00036-2.
Induction of apoptosis by immunosuppressive agents such as glucocorticoids (GCs) and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However, there are few studies which demonstrate the induction of apoptosis by these agents in the activation process of human peripheral blood mononuclear cells (PBMCs). Here we show that potent immunosuppressive GCs and CsA induce apoptosis in concanavalin A (con A)-activated human PBMCs. In this study, GCs and CsA suppressed human PBMC-blastogenesis when activated by con A in a dose-dependent manner, where healthy PBMCs treated with > 100 ng/ml of each immunosuppressive agent exhibited a DNA-ladder structure in electrophoretic analysis. In three chronic renal failure (CRF) patients, dose-dependency of the PBMC-apoptosis induction was confirmed by our quantification of fragmented DNA using ELISA. Furthermore, the enrichment of DNA fragmentation was significantly associated with the rate of PBMC-blastogenesis when treated with GCs or CsA (r = -0.466, P < 0.01). These results suggested that suppression of the mitogen-induced PBMC-blastogenesis by the immunosuppressive agents should be correlated with the induction of apoptosis.
已有研究表明，免疫抑制剂如糖皮质激素（GCs）和环孢素（CsA）可诱导培养的淋巴细胞发生凋亡。然而，很少有研究证明这些药物在人外周血单个核细胞（PBMCs）激活过程中能诱导凋亡。在此，我们发现强效免疫抑制剂GCs和CsA可诱导伴刀豆球蛋白A（con A）激活的人PBMCs发生凋亡。在本研究中，GCs和CsA以剂量依赖方式抑制con A激活的人PBMCs增殖，当用每种免疫抑制剂>100 ng/ml处理健康PBMCs时，电泳分析显示出现DNA梯状结构。在3例慢性肾衰竭（CRF）患者中，通过酶联免疫吸附测定（ELISA）对DNA片段进行定量，证实了PBMCs凋亡诱导的剂量依赖性。此外，用GCs或CsA处理时，DNA片段富集与PBMCs增殖率显著相关（r = -0.466，P < 0.01）。这些结果表明，免疫抑制剂对丝裂原诱导的PBMCs增殖的抑制作用应与凋亡诱导相关。
