Cyclosporin A inhibits degranulation of rat basophilic leukemia cells and human basophils. Inhibition of mediator release without affecting PI hydrolysis or Ca2+ fluxes.
Cyclosporin A inhibits degranulation of rat basophilic leukemia cells and human basophils. Inhibition of mediator release without affecting PI hydrolysis or Ca2+ fluxes.
复制标题
环孢素 A 抑制大鼠嗜碱性白血病细胞和人嗜碱性粒细胞的脱颗粒。
DOI：
10.4049/jimmunol.144.7.2659
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发表时间：
1990
影响因子：
4.4
通讯作者：
R. Hohman
中科院分区：
文献类型：
--
作者：
T. Hultsch;J. L. Rodriguez;M. Kaliner;R. Hohman
环孢素 A (CSA) 在体内达到的 CSA 浓度治疗范围内以剂量依赖性方式抑制大鼠嗜碱性白血病 (RBL) 细胞和人外周血嗜碱性粒细胞 IgE 受体介导的胞吐作用。在 0.2 微克/ml CSA 下观察到半最大抑制。研究了 CSA 对参与受体介导的 RBL 细胞激活的几个生化参数的影响。当在激活前5分钟添加CSA时，分泌受到最大抑制，而当在细胞被触发前2分钟添加药物时，抑制几乎达到最大。当用 A23187（一种钙离子载体）刺激 RBL 细胞时，观察到相同的结果。这些结果表明，除了抑制蛋白质合成之外，还涉及其他机制。即使在细胞被触发之前将 CSA 从缓冲液中除去，CSA 对任一促分泌剂释放的抑制仍然持续。在对血清素释放产生超过 80% 抑制的相同条件下，没有观察到受体介导的磷脂酰肌醇水解、45Ca2+ 摄取或细胞内游离 Ca2+ 浓度升高受到抑制。这些结果表明信号转导的早期事件不受影响，并表明 CSA 的细胞内靶标参与胞吐作用的后期。此外，数据表明 CSA 抑制 T 淋巴细胞以外的细胞，并预测接受 CSA 治疗的患者可能会改变对过敏原的反应。
Cyclosporin A (CSA) inhibits IgE receptor-mediated exocytosis from rat basophilic leukemia (RBL) cells and human peripheral blood basophils in a dose-dependent manner over the therapeutic range of CSA concentrations achieved in vivo. Half-maximal inhibition was observed at 0.2 micrograms/ml CSA. The effect of CSA on several biochemical parameters involved in receptor-mediated activation of RBL cells was examined. Maximum inhibition of secretion occurred when CSA was added 5 min before activation, and inhibition was nearly maximum when the drug was added 2 min before the cells were triggered. The same results were observed when RBL cells were stimulated with A23187, a calcium ionophore. These results suggest a mechanism other than inhibition of protein synthesis is involved. Inhibition by CSA of release by either secretagogue persisted, even if CSA was removed from the buffer before the cells were triggered. No inhibition was observed of either receptor-mediated phosphatidylinositol hydrolysis, 45Ca2+ uptake, or the rise in the intracellular concentration of free Ca2+ under the same conditions that produced greater than 80% inhibition of serotonin release. These results demonstrate that the early events in signal transduction are not affected, and suggest that the intracellular target for CSA participates in a later stage of exocytosis. Furthermore, the data suggest that CSA suppresses cells other than T lymphocytes and predict that patients on CSA therapy may have altered response to allergens.