Hernández-Godoy J, Planelles D, Bayona A, Balsalobre B, González-Molina A
Unidad de Inmunologia Experimental, Hospital La Fe, Valencia, Spain.
Res Exp Med (Berl). 1992;192(6):423-30. doi: 10.1007/BF02576300.
The purpose of this study was to determine the effects that specific inhibition of arachidonic acid (AA) metabolism has on the antibody-dependent cellular cytotoxicity (ADCC) of murine spleen cells. The action of three inhibitors of the lipoxygenase (LO) pathway--nordihydroguaiaretic acid (NDGA), esculetin (Es), and phenanthroline (Phe)--was compared with that of three inhibitors of the cyclooxygenase (CO) pathway--indomethacin (INDO), acetyl salicylic acid (ASA), and imidazole (IMI). All the LO inhibitors suppressed ADCC function in a dose-dependent manner, but NDGA was the most potent inhibitor of this cytolytic activity. In fact, NDGA inhibited the ADCC function with 97% inhibition at 100 microM, while Phe and Es, at the same concentration, inhibited ADCC by 21% and 19%, respectively. However, CO inhibitors did not markedly affect ADCC function and only some doses of them had a slight, but significant, depressing effect (8-11% inhibition at 0.01-0.1 microM of INDO, 7% inhibition at 400 microM of ASA, and 13% inhibition at 800-1000 microM of IMI). These results suggest the LO pathway of the arachidonic acid metabolism plays an important role in regulating ADCC activity of murine spleen cells and the products of the CO pathway have little effect on ADCC lysis.
本研究的目的是确定特异性抑制花生四烯酸（AA）代谢对小鼠脾细胞抗体依赖性细胞毒性（ADCC）的影响。比较了脂氧合酶（LO）途径的三种抑制剂——去甲二氢愈创木酸（NDGA）、七叶亭（Es）和菲咯啉（Phe）——与环氧化酶（CO）途径的三种抑制剂——吲哚美辛（INDO）、乙酰水杨酸（ASA）和咪唑（IMI）——的作用。所有LO抑制剂均以剂量依赖性方式抑制ADCC功能，但NDGA是这种细胞溶解活性最有效的抑制剂。事实上，NDGA在100 microM时以97%的抑制率抑制ADCC功能，而在相同浓度下，Phe和Es分别以21%和19%的抑制率抑制ADCC。然而，CO抑制剂并未显著影响ADCC功能，只有部分剂量具有轻微但显著的抑制作用（INDO在0.01 - 0.1 microM时抑制率为8 - 11%，ASA在400 microM时抑制率为7%，IMI在800 - 1000 microM时抑制率为13%）。这些结果表明，花生四烯酸代谢的LO途径在调节小鼠脾细胞的ADCC活性中起重要作用，而CO途径的产物对ADCC裂解作用很小。
