Does the binding of cyclosporine to calmodulin result in immunosuppression?
Does the binding of cyclosporine to calmodulin result in immunosuppression?
复制标题
环孢素与钙调蛋白的结合是否会导致免疫抑制？
DOI：
10.1126/science.3749892
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Dedman,JR
中科院分区：
文献类型：
--
作者：
LeGrue,SJ;Turner,R;Weisbrodt,N;Dedman,JR
环孢菌素类是一个家族的环状十一肽，在体外和体内都能引起对原发性免疫刺激的深刻抑制。最近，调节蛋白钙调素（CaM）已被牵连作为环孢菌素A（CsA）结合的目标。本研究利用CsA的两种活性较低的异构体来评估CaM结合的特异性和生物学意义。这三种环孢菌素在体外与钙调素的结合力相当，与免疫抑制活性无关。此外，钙调素依赖性酶系统抑制活性和非活性环孢菌素，但只有在浓度为100倍的必要阻断淋巴细胞活化。因此，环孢菌素异构体显示的精致的免疫抑制立体特异性并没有反映在钙调素的结合和抑制，这表明钙调素依赖性过程的抑制不足以解释CsA的免疫抑制活性。
The cyclosporines are a family of cyclic endecapeptides that cause a profound suppression of primary immune stimulation both in vitro and in vivo. Recently, the regulatory protein calmodulin (CaM) has been implicated as a target for cyclosporin A (CsA) binding. This study utilized two less-active isomers of CsA to evaluate the specificity and biological significance of CaM binding. The three cyclosporines exhibited equivalent in vitro binding to CaM, regardless of immunosuppressive activity. Furthermore, CaM-dependent enzyme systems were inhibited equally by active and inactive cyclosporines, but only at concentrations 100 times those necessary to block lymphocyte activation. Thus the exquisite immunosuppressive stereospecificity displayed by cyclosporine isomers is not reflected in the binding to and inhibition of CaM, suggesting that inhibition of CaM-dependent processes is not sufficient to explain the immunosuppressive activity of CsA.