Liver-associated macrophage precursors as natural cytotoxic effectors against Candida albicans and Yac-1 cells.

Liver nonparenchymal cells of maleic anhydride divinyl ether or cyclophosphamide-treated mice were assayed for cytotoxic activity against the yeast form of Candida albicans. A strong increase in this activity was observed after both in vivo treatments, as compared to untreated control mice. The effector cell was enriched by nylon wool passage and separation of nonadherent liver nonparenchymal cells on a discontinuous Percoll gradient. By means of direct and indirect rosetting techniques, based on the presence of Fc receptors and the F4/80 and M143 macrophage surface markers, we could separate a nearly homogeneous effector cell population. It displayed, besides the candidacidal activity, Fc receptors and the M143 and F4/80 antigens, also strong natural cytotoxicity against Yac-1 lymphoma cells. When cultured in medium containing colony-stimulating factor-1, this effector population reacted with a strong proliferative response as measured through incorporation of tritiated thymidine. The data presented show that nonadherent, nonphagocytic macrophage precursors, which we characterized previously from in vitro bone marrow cultures, occur in vivo as organ-associated effector cells in the liver after elicitation with maleic anhydride divinyl ether or cyclophosphamide. These macrophage precursors have prior to their maturation the ability to serve as a microbicidal and tumoricidal natural killer cell.