Helfand S L, Werkmeister J, Roder J C
J Exp Med. 1982 Aug 1;156(2):492-505. doi: 10.1084/jem.156.2.492.
The binding of tumor cells or fetal fibroblasts to human natural killer (NK) cells led to a rapid chemiluminescence response within seconds of target-effector interaction. The degree of chemiluminescence was dependent on the concentration of NK-enriched lymphocytes or target cells, and plasma membrane vesicles from K562 also induced a chemiluminescence response. Mild glutaraldehyde treatment of effector cells abrogated their ability to generate chemiluminescence, whereas K562 target cells treated in the same way were almost fully able to induce a chemiluminescence response to NK-enriched lymphocytes. These results show a directionality of response with NK as the responders and tumor cells as the stimulators. A survey of eight different tumor cell lines and fetal fibroblast lines revealed a striking correlation (r greater than 0.93, P less than 0.001) between the ability of a given line to bind to NK-enriched lymphocytes, induce chemiluminescence, and to be lysed. Three differentiated sublines of K562 grown in butyrate and cloned induced little chemiluminescence compared with the K562 parent, and they were selectively resistant to NK-mediated binding and cytolysis. In addition, treatment of K562 cells with higher concentrations of glutaraldehyde for longer periods led to varying degrees of target antigen preservation, as measured in cold target competition assays and in conjugate formation. The degree of NK target antigen preservation correlated directly with the ability of the cells to induce chemiluminescence (r greater than 0.95). The degree of NK activation was also important because interferon-pretreated effectors generated more chemiluminescence upon stimulation with K562 or MeWo targets. Monocytes or granulocytes did not contribute to the chemiluminescence induced by NK-sensitive targets. Some NK-resistant tumor cell lines were sensitive to monocyte-mediated cytolysis and also induced chemiluminescence in monocytes but not NK cells. These results show that the target structures recognized by the NK cell may play a role in NK activation because the degree of chemiluminescence was directly proportional to the ability of a given target cell line to bind to the NK cell and to be lysed.
肿瘤细胞或胎儿成纤维细胞与人自然杀伤（NK）细胞的结合在靶细胞与效应细胞相互作用的数秒内引发了快速的化学发光反应。化学发光的程度取决于富含NK的淋巴细胞或靶细胞的浓度，并且来自K562的质膜囊泡也能诱导化学发光反应。用轻度戊二醛处理效应细胞会消除其产生化学发光的能力，而以同样方式处理的K562靶细胞几乎完全能够诱导对富含NK的淋巴细胞产生化学发光反应。这些结果显示了以NK作为反应者和肿瘤细胞作为刺激者的反应方向性。对八种不同肿瘤细胞系和胎儿成纤维细胞系的调查显示，给定细胞系与富含NK的淋巴细胞结合、诱导化学发光以及被裂解的能力之间存在显著相关性（r大于0.93，P小于0.001）。与K562亲本相比，在丁酸盐中生长并克隆的K562的三个分化亚系几乎不诱导化学发光，并且它们对NK介导的结合和细胞溶解具有选择性抗性。此外，用更高浓度的戊二醛长时间处理K562细胞导致靶抗原不同程度的保留，这在冷靶竞争试验和共轭形成中得以测量。NK靶抗原保留的程度与细胞诱导化学发光的能力直接相关（r大于0.95）。NK激活的程度也很重要，因为经干扰素预处理的效应细胞在用K562或MeWo靶细胞刺激时会产生更多的化学发光。单核细胞或粒细胞对NK敏感靶细胞诱导的化学发光没有贡献。一些NK抗性肿瘤细胞系对单核细胞介导的细胞溶解敏感，并且也在单核细胞中诱导化学发光，但在NK细胞中不诱导。这些结果表明，NK细胞识别的靶结构可能在NK激活中起作用，因为化学发光的程度与给定靶细胞系与NK细胞结合并被裂解的能力成正比。
