Chow D A
Immunology Department, University of Manitoba, Winnipeg.
Cell Immunol. 1990 Apr 15;127(1):172-86. doi: 10.1016/0008-8749(90)90123-9.
Natural killer (NK) cell-resistant tumors exist despite their ability to bind cells from the effector population. Tumor sensitivity to NK activity was therefore examined at the level of susceptibility to cytolysin-containing NK cell cytotoxic granule extracts. The NK-sensitive SL2-5 murine lymphoma was markedly more susceptible than the NK-resistant L5178Y-F9 to solubilized granule preparations from the rat NK tumor cell line RNK-16, and this corresponded also with tumor sensitivity to hypotonic lysis. However, the resistant L5178Y-F9 was better able to inhibit the extract activity than the SL2-5. Dissociation of the binding and lysis phases of the cytolysin reaction based on their differential temperature requirements, 4 degrees C for binding and 37 degrees C for lysis, permitted an examination of the cytolysin/tumor interaction prior to lysis. The residual cytotoxic activity was lower after extract exposure to the L5178Y-F9 compared with the SL2-5 consistent with possible inhibitor production. Finally, supernatant material collected from the L5178Y-F9 was a better inhibitor of granule extract lysis and acted preferentially in the extract-binding phase. The inhibitor appears to be protein in nature, relatively stable, and exhibits molecular weight heterogeneity ranging from 2000 to greater than 300,000.
尽管天然杀伤（NK）细胞能够与效应细胞群体结合，但仍存在对NK细胞具有抗性的肿瘤。因此，在对含溶细胞素的NK细胞细胞毒性颗粒提取物的敏感性水平上，检测了肿瘤对NK活性的敏感性。对NK敏感的SL2-5小鼠淋巴瘤对来自大鼠NK肿瘤细胞系RNK-16的溶解颗粒制剂的敏感性明显高于对NK有抗性的L5178Y-F9，这也与肿瘤对低渗裂解的敏感性相对应。然而，有抗性的L5178Y-F9比SL2-5更能抑制提取物的活性。基于溶细胞素反应的结合和裂解阶段对温度的不同要求（结合阶段为4℃，裂解阶段为37℃），对二者进行解离，使得在裂解之前能够检测溶细胞素与肿瘤的相互作用。与SL2-5相比，提取物与L5178Y-F9接触后，残余细胞毒性活性较低，这与可能产生抑制剂一致。最后，从L5178Y-F9收集的上清液物质是颗粒提取物裂解的更好抑制剂，并且优先在提取物结合阶段起作用。该抑制剂似乎本质上是蛋白质，相对稳定，并且表现出分子量异质性，范围从2000到大于300,000。
