COMPLEX CA-2+ FLUX INHIBITION AS PRIMARY MECHANISM OF STAUROSPORINE-INDUCED IMPAIRMENT OF T-CELL ACTIVATION
COMPLEX CA-2+ FLUX INHIBITION AS PRIMARY MECHANISM OF STAUROSPORINE-INDUCED IMPAIRMENT OF T-CELL ACTIVATION
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DOI：
10.1002/eji.1830190807
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发表时间：
1989-08-01
影响因子：
5.4
通讯作者：
SCHEUER, W
中科院分区：
文献类型：
--
作者：
KUBBIES, M;GOLLER, B;SCHEUER, W
采用多参数流式细胞术研究了高效药物staurosporine对人外周血T淋巴细胞早期激活信号Ca2+通量的抑制作用。据报道，Staurosporine是蛋白激酶c的特异性抑制剂。然而，我们发现，当浓度在1.0和10.0 ng/ml之间时，它可以抑制抗cd3和植物血凝素刺激的人CD4+和CD8+淋巴细胞中的Ca2+内流。Staurosporine减少Ca2+阳性CD4+和CD8+淋巴细胞的数量以及每个细胞的Ca2+内流；该药物还延迟了对多克隆刺激的最大反应时间。此外，我们证明了司陶孢素通过抑制CD4+和CD8+淋巴细胞从内质网释放膜结合的Ca2+来影响初级Ca2+反应。抗cd3抗体与T淋巴细胞的结合研究表明，在staurosporine存在下，T淋巴细胞具有正常的结合能力。关于通过磷脂酶C激活T细胞的经典方案，我们的数据表明，星孢素可能主要通过其对早期Ca2+通量信号的影响来抑制T细胞的激活。
The inhibitory effect of the highly effective drug staurosporine on the early activation signal Ca2+ flux was investigated via multiparameter flow cytometry in human peripheral blood T lymphocytes. Staurosporine has been reported to be a specific inhibitor of protein kinase C. However, we show that it inhibits the Ca2+ influx in anti-CD3 and phytohemagglutinin-stimulated human CD4+ and CD8+ lymphocytes at concentrations between 1.0 and 10.0 ng/ml. Staurosporine decreases the number of Ca2+-positive CD4+ and CD8+ lymphocytes as well as the Ca2+ influx per cell; the drug also delays the time of the maximum response to polyclonal stimulation. In addition, we demonstrate that staurosporine affects the primary Ca2+ response via inhibition of the release of the membrane-bound Ca2+ from the endoplasmic reticulum in CD4+ and CD8+ lymphocytes. Binding studies of the anti-CD3 antibody to T lymphocytes indicate normal binding capacities in the presence of staurosporine. With respect to the classical scheme of T cell activation via phospholipase C, our data suggest that staurosporine may inhibit T cell activation primarily by its effect on the early Ca2+ flux signal.