Quan P C, Ishizaka T, Bloom B R
J Immunol. 1982 Apr;128(4):1786-91.
The mechanism of cytolysis by murine NK cells was analyzed using a variety of metabolic inhibitors that have proven informative in studying the lytic mechanism of CTL and the mechanism of histamine release by mast cells. Target cell binding occurred in the absence of calcium and was inhibited by only one of the agents studied, cytochalasin B. Lysis was initiated by addition of Ca2+ ions, as in the case of CTL. Subsequent to target cell binding, but prior to programming for lysis by Ca2+, NK cell lytic activity could be suppressed by inhibitors of chymotrypsin-like, but not trypsin-like proteases, in contrast to CTL. In addition, 3-deaza-SIBA, an inhibitor of transmethylation reactions and quinacrine, an inhibitor of phospholipase A2, appear to act before the Ca2+-dependent programming for lysis. Sr2+ ions blocked the lytic function, as did trifluoperazine (stelazine), the former presumably competing for ionic calcium, the latter known to block binding of Ca2+ to calmodulin. 8Br-cAMP and colchicine blocked later steps required for lysis. With the possible exception of trifluoperazine, all of the agents that blocked NK cell lysis are known to inhibit histamine release from mast cells. These results lend support to the stimulus-secretion model, originally proposed to explain the mechanism of CTL cytolysis, as relevant to the mechanism of lysis by NK cells.
利用多种代谢抑制剂分析了小鼠自然杀伤（NK）细胞的细胞溶解机制，这些抑制剂在研究细胞毒性T淋巴细胞（CTL）的溶解机制和肥大细胞组胺释放机制方面已被证明具有指导意义。在无钙条件下发生靶细胞结合，并且仅被所研究的一种试剂细胞松弛素B抑制。如CTL的情况一样，通过添加Ca2+离子启动溶解。与CTL相反，在靶细胞结合之后，但在由Ca2+编程进行溶解之前，NK细胞的溶解活性可被类胰凝乳蛋白酶而非类胰蛋白酶的蛋白酶抑制剂抑制。此外，转甲基化反应抑制剂3-脱氮-SIBA和磷脂酶A2抑制剂喹吖因似乎在Ca2+依赖性溶解编程之前起作用。Sr2+离子阻断溶解功能，三氟拉嗪（甲硫哒嗪）也如此，前者可能竞争离子钙，后者已知可阻断Ca2+与钙调蛋白的结合。8-溴-环磷酸腺苷（8Br-cAMP）和秋水仙碱阻断溶解所需的后续步骤。除三氟拉嗪外，所有阻断NK细胞溶解的试剂均已知可抑制肥大细胞组胺释放。这些结果支持了最初提出用于解释CTL细胞溶解机制的刺激-分泌模型，该模型与NK细胞的溶解机制相关。
