人类自然杀伤的调节。IV. 脂氧合酶在自然杀伤活性调节中的作用。

Regulation of human natural killing. IV. Role of lipoxygenase in regulation of natural killing activity.

作者信息

Leung K H, Ip M M, Koren H S

出版信息

Scand J Immunol. 1986 Oct;24(4):371-80. doi: 10.1111/j.1365-3083.1986.tb02124.x.

DOI:10.1111/j.1365-3083.1986.tb02124.x

Abstract

In this study we demonstrated that natural killer (NK) cell lysis by human peripheral blood nonadherent (NA) cells against K562 target cells was rapidly inhibited by four agents that inhibit the lipoxygenase pathway of arachidonic acid metabolism, nordihydroguaiaretic acid (NDGA), U-60257, alpha-phenanthroline, and esculetin. However, human NK cells activated by interferons (IFN) or poly I:C were partially resistant to suppression by NDGA and U-60257. Pretreatment of the NA cells with the four lipoxygenase inhibitors at 37 degrees C for 18 h led to suppression of NK activity. The inhibition of NK activity by NDGA was not reversed by aspirin at a concentration that inhibits PGE2 synthesis. Thus, suppression of NK activity by NDGA was not mediated by the effects on PGE2 synthesis. However, the inhibition of endogenous NK activity by NDGA, U-60257, alpha-phenanthroline, or esculetin was partially reversed by IFN or poly I:C. These results suggest that products of lipoxygenation are required for maintenance of human NK activity.

摘要

在本研究中，我们证明了人外周血非贴壁（NA）细胞对K562靶细胞的自然杀伤（NK）细胞裂解作用，会被四种抑制花生四烯酸代谢脂氧合酶途径的试剂迅速抑制，这四种试剂分别是去甲二氢愈创木酸（NDGA）、U-60257、α-菲咯啉和七叶亭。然而，被干扰素（IFN）或聚肌胞苷酸（poly I:C）激活的人NK细胞对NDGA和U-60257的抑制作用具有部分抗性。将NA细胞与这四种脂氧合酶抑制剂在37℃下预处理18小时会导致NK活性受到抑制。NDGA对NK活性的抑制作用不会被抑制PGE2合成的阿司匹林浓度所逆转。因此，NDGA对NK活性的抑制作用不是由对PGE2合成的影响介导的。然而，IFN或poly I:C可部分逆转NDGA、U-60257、α-菲咯啉或七叶亭对内源性NK活性的抑制作用。这些结果表明，脂氧合产物是维持人NK活性所必需的。