EFFECTS OF PLASMODIUM-VINCKEI HEMOZOIN ON THE PRODUCTION OF OXYGEN RADICALS AND NITROGEN-OXIDES IN MURINE MACROPHAGES

When murine peritoneal macrophages were loaded in vitro with Plasmodiu m vinckei hemozoin and stimulated with opsonized zymosan for 90 min or with lipopolysaccharide and/or murine interferon-gamma for 24 hr, sig nificant decreases in the production of oxygen radicals and nitrogen o xides, respectively, could be detected by comparison with macrophages without hemozoin. Moreover, nonradioactive in situ hybridization and i mmunohistologic analysis in liver sections of P. vinckei-infected mice with more than 60% parasitemia showed that liver cells were still exp ressing considerable levels of inducible nitric oxide synthase in the late phase of murine malaria, but most of the liver macrophages presen ting accumulation of malaria pigment were negative in this analysis. T hese results further Indicate that malaria pigment accumulation may be responsible for toxicity and impairment of macrophage functions durin g murine malaria.