Leung K H
E. I. du Pont de Nemours and Co., Medical Products Department, Glenolden, Pennsylvania 19036.
Cell Immunol. 1988 Jul;114(2):359-69. doi: 10.1016/0008-8749(88)90328-0.
We have investigated the role of arachidonic acid (AA) metabolism in natural killer (NK) cell activity. Human nonadherent (NA) peripheral blood lymphocytes were used as effector cells against 51Cr-labeled K562 target cells. Synthesis of leukotriene C4 (LTC4) is dependent on glutathione S-transferase (GST). We have chosen to study three putative GST inhibitors, namely, ethacrynic acid (ET), caffeic acid (CA), and ferulic acid (FA), with regard to NK activity and with regard to their effect on AA metabolism. The GST inhibitors inhibited NK lysis when added directly to the NK assay. The GST inhibitors inhibited LTC4 synthesis as induced by calcium ionophore A23187 in a dose-dependent manner similar to their inhibition of NK activity. However, only ET was selective, for it had little effect on LTB4, 5-hydroxyeicosatetraenoic acid, and prostaglandin E2 synthesis. LTC4 synthesis was associated with the NK-enriched fractions obtained from discontinuous Percoll gradients. NK-specific anti-Leu-11b antibody and C treatment could abrogate NK activity and LTC4 synthesis. ET was also inhibitory when NA cells were cultured at 37 degrees C for 18 hr. In this case, LTC4 could reverse the inhibitory effect of ET. Our data suggest that LTC4 plays an important role in NK activity.
我们研究了花生四烯酸（AA）代谢在自然杀伤（NK）细胞活性中的作用。使用人非贴壁（NA）外周血淋巴细胞作为针对51Cr标记的K562靶细胞的效应细胞。白三烯C4（LTC4）的合成依赖于谷胱甘肽S-转移酶（GST）。我们选择研究三种假定的GST抑制剂，即依他尼酸（ET）、咖啡酸（CA）和阿魏酸（FA），观察它们对NK活性以及对AA代谢的影响。将GST抑制剂直接添加到NK测定中时，它们会抑制NK细胞的裂解作用。GST抑制剂以剂量依赖的方式抑制钙离子载体A23187诱导的LTC4合成，这与其对NK活性的抑制作用相似。然而，只有ET具有选择性，因为它对LTB4、5-羟基二十碳四烯酸和前列腺素E2的合成影响很小。LTC4的合成与从不连续Percoll梯度获得的富含NK细胞的组分相关。NK特异性抗Leu-11b抗体和C处理可消除NK活性和LTC4合成。当NA细胞在37℃培养18小时时，ET也具有抑制作用。在这种情况下，LTC4可以逆转ET的抑制作用。我们的数据表明LTC4在NK活性中起重要作用。
