Effects of changes in membrane potential on the cyclosporin-induced inhibition of T-cell proliferation.
Effects of changes in membrane potential on the cyclosporin-induced inhibition of T-cell proliferation.
复制标题
膜电位变化对环孢菌素诱导的 T 细胞增殖抑制的影响。
DOI：
10.1016/s0006-291x(05)80994-5
复制
发表时间：
1992
影响因子：
3.1
通讯作者：
Gelfand,EW
中科院分区：
文献类型：
--
作者：
Tordai,A;Or,R;Gelfand,EW
环孢菌素A（CsA）主要通过抑制T淋巴细胞增殖发挥其免疫抑制作用。其行动的确切机制和目标尚未完全确定。CsA还已知诱导T淋巴细胞中的快速膜去极化。我们已经测试了CsA依赖性去极化在药物抑制T细胞增殖中的作用。在这些研究中，诱导的膜去极化（短杆菌肽的存在下，或通过更换的Na+含量的介质与K+）或超极化（在缬氨霉素的存在下）没有影响的诱导T细胞的能力佛波醇二丁酸/离子霉素或亚有丝分裂浓度的PHA，CsA免疫抑制的目标。然而，无论在诱导T细胞能力的膜电位的状态，CsA的抑制是相同的，在正常极化细胞中看到的。我们的结论是CsA诱导的去极化不是其抑制T细胞增殖的关键因素。
Cyclosporin A (CsA) exerts its major immunosuppressive effect by inhibition of T-lymphocyte proliferation. The precise mechanism and target of its action has not yet been completely identified. CsA is also known to induce a rapid membrane depolarization in T lymphocytes. We have tested the role of CsA-dependent depolarization in the inhibition of T-cell proliferation by the drug. In these studies, induced membrane depolarization (in the presence of gramicidin or by replacing the Na+content of the medium with K+) or hyperpolarization (in the presence of valinomycin) had no influence on the induction of T-cell competence by phorbol dibutyrate/ionomycin or by submitogenic concentrations of PHA, a target for CsA immunosuppression. However, regardless of the state of membrane potential during the induction of T-cell competence, the inhibition by CsA was the same as seen in normally polarized cells. We conclude that the depolarization induced by CsA is not a critical element in its inhibitory effect on T-cell proliferation.