title: Interaction of Leishmania with a macrophage cell line. Correlation between intracellular killing and the generation of oxygen intermediates.
abstract: 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.
mesh_terms: D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007111:Immunity, Cellular; D007891:Leishmania / Q000276:immunology*; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D010101:Oxygen Consumption; D010587:Phagocytosis
chemical_list: D008222:Lymphokines; D006861:Hydrogen Peroxide; D005947:Glucose