Role of Macrophages in the Augmentation of Mouse Natural Killer Cell Activity by Poly I:C and Interferon

Abstract

Abstract Mouse natural killer (NK) cell activity is readily augmented by interferon (IF) and IF inducers. To further our understanding of the regulation of NK activity by IF and poly I:C, we have investigated the cell types involved in in vivo and in vitro augmentation by these agents. Removal or inactivation of macrophages by silica, carrageenan, passage through rayon columns, or by the carbonyl iron-magnet technique before poly I:C treatment significantly depressed the augmentation of NK activity. In parallel, such treatments also decreased the level of IF induced by poly I:C. These observations were made in both conventional and nude mice. After induction of NK activity and IF by poly I:C, the removal of macrophages had no effect on the outcome of the activity. When a macrophage cell line, PU5 1.8, was treated with poly I:C, the culture fluid contained high concentrations of IF that were able to boost substantially NK activity in fresh spleen cells above the control level. Moreover, normal macrophages pretreated with poly I:C were able to produce IF by themselves and boost NK activity in fresh spleen cells. All these data taken together indicated that the requirement for macrophages in the boosting of NK activity by poly I:C was related to the need for these cells for the production of IF. In contrast, removal or inactivation of macrophages had no effect on the induction of NK activity by IF. Therefore, it appears that IF acts directly on NK cells to increase their function and that macrophages may play a secondary role, by production of IF, in response to inducers such as poly I:C.