INHIBITION OF NATURAL-KILLER CELL-MEDIATED CYTO-TOXICITY BY ML-9, A SELECTIVE INHIBITOR OF MYOSIN LIGHT CHAIN KINASE
INHIBITION OF NATURAL-KILLER CELL-MEDIATED CYTO-TOXICITY BY ML-9, A SELECTIVE INHIBITOR OF MYOSIN LIGHT CHAIN KINASE
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DOI：
10.1016/0192-0561(89)90070-2
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发表时间：
1989-01-01
期刊：
影响因子：
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通讯作者：
SHIGETA, S
中科院分区：
文献类型：
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作者：
ITO, M;TANABE, F;SHIGETA, S
为探讨微丝在自然杀伤(NK)细胞介导的细胞毒作用中的作用，在NK细胞检测系统中检测了常用的微丝抑制剂细胞松弛素B、D和二氢细胞松弛素B，以及调节微丝收缩的选择性肌球蛋白轻链激酶抑制剂1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1，4-diazepine盐酸盐(ML-9)。ML-9以剂量依赖的方式抑制NK细胞的活性，但不影响靶细胞的结合，而细胞松弛素则抑制这种结合。葡聚糖悬浮法显示，ML-9抑制裂解过程中裂解阶段的编程。在单细胞实验中，在靶细胞结合发生后加入ML-9抑制结合的靶细胞的裂解，而以类似的方式加入细胞松弛素不影响结合的靶细胞的裂解。因此，这些结果提示微丝收缩可能参与了NK细胞介导的细胞溶解的溶解机制。然而，细胞松弛素抑制靶细胞结合的机制尚不清楚。
To investigate the role of microfilaments in natural killer (NK) cell-mediated cytotoxicity, general microfilament inhibitors, cytochalasins B,D and dihydrocytochalasin B, and a selective inhibitor of myosin light chain kinase (MLCK) which regulates microfilament contraction, i.e. 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) were examined in an NK assay system. ML-9 inhibited NK cell activity in a dose-dependent manner without affecting target cell binding, whereas cytochalasins suppressed the binding. The dextran suspension method revealed that ML-9 inhibits the programming for the lysis stage of the lytic process. In the single cell assay, the addition of ML-9 after target cell binding had occurred inhibited the lysis of bound target cells, whereas the addition of cytochalasins in a similar manner did not affect it. Thus, these results suggest that possibility that microfilament contraction is involved in the lytic mechanism of NK cell-mediated cytolysis. However, the mechanism whereby cytochalasins inhibit target cell binding remains unclear.