Effects of nordihydroguaiaretic acid on murine antibody-dependent cellular cytotoxicity

The purpose of this study was to analyze the effects of nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway of arachidonic acid, on antibody-dependent cellular cytotoxicity. Antibody-dependent cellular cytotoxicity mediated by murine spleen cells was significantly inhibited by concentrations of nordihydroguaiaretic acid from 10(-5) to 10(-4) M (1C50 = 2 x 10(-5) M). The inhibitory effect of nordihydroguaiaretic acid was also observed on antibody-dependent cellular cytotoxicity mediated by macrophage-depleted spleen cells as well as isolated macrophages. Nordihydroguaiaretic acid was highly effective when added at the beginning of the assay and was always present throughout the assay, but failed to inhibit the binding of effector and target cells. The inhibition produced by nordihydroguaiaretic acid could not be reversed by leukotriene B4, a 5-lipoxygenase product. These results suggest that arachidonic acid metabolites other than leukotriene B4 are released by different populations of spleen cells to positively regulate important events in the postbinding phase of murine antibody-dependent cellular cytotoxicity.