Interaction of Leishmania with a macrophage cell line. Correlation between intracellular killing and the generation of oxygen intermediates

The promastigote form of Leishmania donovani and Leishmania tropica, the etiologic agents of visceral and cutaneous leishmaniasis, respectively, readily parasitize unstimulated J774G8 macrophage-like cells, whereas 80-95% of the same promastigotes are killed within resident macrophages from normal BALB/c mice. This striking difference in intracellular anti-leishmanial activity correlated closely with the capacity to generate toxic oxygen intermediates. Thus, after triggering with phorbol myristate acetate or phagocytosis of zymosan or promastigotes, 90% of the J774G8 cells failed to reduce nitroblue tetrazolium, and released 5-10-fold less O2- and H2O2 than BALB/c macrophages. Exposure to concanavalin A-stimulated lymphokine, however, effectively enhanced the oxidative response of J774G8 cells, and, similarly, induced intracellular anti-leishmanial activity. Inhibiting macrophage H2O2 production consistently decreased the killing of Leishmania by lymphokine-treated J774G8 cells. These observations illustrate the usefulness of examining homogeneous macrophage cell lines that are deficient in a particular effector function, and also serve reemphasize the important role of oxygen intermediates in the microbicidal response of mononuclear phagocytes to intracellular parasites.