Compared mechanisms of tumor cytolysis by human natural killer cells and activated polymorphonuclear leukocytes.
Compared mechanisms of tumor cytolysis by human natural killer cells and activated polymorphonuclear leukocytes.
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比较人类自然杀伤细胞和活化的多形核白细胞的肿瘤细胞溶解机制。
DOI：
10.4049/jimmunol.132.6.3192
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发表时间：
1984
影响因子：
4.4
通讯作者：
Z. Brahmi
中科院分区：
文献类型：
--
作者：
S. Abrams;Z. Brahmi
自然杀伤（NK）细胞介导的细胞毒性（CMC）的机制在很大程度上仍然是未知的。在这项研究中，我们研究了NK敏感靶细胞（TC） K562刺激后人类NK细胞表现出氧化爆裂（OB）的可能性。过氧化氢酶（CAT）或超氧化物歧化酶（SOD）加入nk介导的细胞毒实验对NK-CMC没有影响。相比之下，CAT和SOD可有效调节phorpol -12-肉豆蔻酸-13-乙酸酯（PMA）激活的多形核白细胞（PMNL）对包括K562在内的三种不同肿瘤TC的细胞毒性。而SOD则增强了pma激活的pmnl介导的细胞毒性。SOD和PMA的协同作用被CAT呈剂量依赖性地抑制。此外，通过化学发光（CL）和sod抑制细胞色素c的减少，我们未能检测到与k562刺激的NK细胞相关的OB。然而，PMNL对PMA （10 ng/ml）反应迅速，在20分钟内产生近10(6)个cpm，在30分钟内分别产生26.7 nM O-2/10(6)个细胞，分别通过CL和细胞色素c的减少检测。最后，在效应细胞与靶细胞（EC:TC）比例为1:1和1:10的细胞浓度下，K562单独降低了细胞色素c，但这种降低不受SOD的抑制，从而表明它具有diaphorase活性。总的来说，我们发现：a)人类NK细胞和pma激活的PMNL对肿瘤细胞的破坏是由不同的机制介导的；b)针对敏感TC的NK-CMC不涉及OB。
The mechanism(s) of natural killer (NK) cell-mediated cytotoxicity (CMC) remains largely unknown. In this study, we investigated the possibility of human NK cells to exhibit an oxidative burst (OB) after stimulation by K562, an NK-sensitive target cell (TC). The addition of catalase (CAT) or superoxide dismutase (SOD) to the NK-mediated cytotoxic assay had no effect on NK-CMC. In contrast, CAT and SOD effectively modulated the cytotoxicity mediated by phorbol-12-myristate-13-acetate (PMA)-activated polymorphonuclear leukocytes (PMNL) against three different tumor TC, including K562. CAT abrogated, while SOD enhanced PMA-activated PMNL-mediated cytotoxicity. The synergistic effect of SOD and PMA was suppressed in a dose-dependent fashion by CAT. Furthermore, by chemiluminescence (CL) and SOD-inhibitable reduction of cytochrome c, we failed to detect an OB associated with K562-stimulated NK cells. PMNL, however, rapidly responded to PMA (10 ng/ml), generating almost 10(6) cpm within 20 min and 26.7 nM O-2/10(6) cells/30 min, as detected by CL and reduction of cytochrome c, respectively. Finally, K562 alone, at cell concentrations corresponding to effector cell:target cell (EC:TC) ratios of 1:1 and 1:10, reduced cytochrome c, but this reduction was not inhibited by SOD, thus suggesting a diaphorase activity. Overall, we show that: a) tumor cell destruction by human NK cells and by PMA-activated PMNL is mediated by different mechanisms; and b) NK-CMC against a sensitive TC does not involve an OB.