Target-effector cell interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes.
Target-effector cell interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes.
复制标题
自然杀伤细胞系统中的靶效应细胞相互作用。
作者：
J. Roder;S. Argov;M. Klein;C. Petersson;R. Kiessling;K. Andersson;M. Hansson
使用各种抑制剂进一步研究自然杀伤的机制，并将其与细胞毒性T淋巴细胞（CTL）的淋巴溶解进行比较。呼吸抑制剂DNP和NaN 3或低温（0度）阻断CTL系统中靶-效应物相互作用的细胞接触相，但不阻断NK系统。如先前在CTL系统中所示，在NK系统中，裂解阶段也被糖酵解抑制剂碘乙酸盐和NaF抑制。偶极溶剂二甲基亚砜和微管破坏剂细胞松弛素B可抑制NK靶点结合。用戊二醛（一种蛋白质交联剂）预处理NK细胞完全阻止了裂解，但不能形成靶向效应物缀合物。氯喹可抑制NK细胞的裂解相，并抑制溶酶体酶的功能。溶酶体缺陷的米色突变小鼠也完全缺乏NK溶解功能，并且这种缺陷不能用cGMP恢复。T细胞和巨噬细胞介导的细胞溶解先前显示在米色小鼠中相对正常。这些结果表明，（i）NK细胞溶解的机制是一个复杂的，多步骤的过程，和（ii）这个过程是根本不同的发生在CTL。一个“刺激分泌”模型的NK细胞溶解，它是假设，溶酶体酶可能是溶解分子。
Various inhibitors were used to study further the mechanism of natural killing and to compare it to lympholysis by cytotoxic T lymphocytes (CTL). The respiratory inhibitors DNP and NaN3 or low temperatures (0 degrees) blocked the cell contact phase of target-effector interaction in the CTL system but not the NK system. The lytic stage was also inhibited by the glycolytic inhibitors, iodoacetate and NaF, in the NK system as previously shown in the CTL system. Dimethylsulphoxide, a dipolar solvent, and cytochalasin B, a microtubule disruptor, inhibited NK target binding. Pre-treatment of Nk cells with glutaraldehyde, a protein cross-linking agent, completely prevented lysis, but not the formation of target-effector conjugates. The lytic phase of NK lysis was inhibited by chloroquine which also inhibited lysosomal enzyme function. Lysosome defective, beige mutant mice were also totally deficient in NK lytic function and this defect could not be restored with cGMP. T-cell and macrophage mediated cytolysis was previously shown to be relatively normal in beige mice. These results suggest that (i) the mechanism of NK cytolysis is a complex, multistep process, and (ii) this process is fundamentally different from that occurring in CTL. A 'stimulus-secretion' model of NK cytolysis is presented in which it is postulated that lysosomal enzymes may be the lytic molecules.