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

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.