Oxidative killing of the intraerythrocytic malaria parasite Plasmodium yoelii by activated macrophages.
The capacity of macrophages activated in vivo and in vitro to kill Plasmodium yoelii was investigated. Macrophages activated by BCG-, Con A-, or malaria-induced lymphokines (LK) were cultured with P. yoelii-parasitized erythrocytes (PE). In some experiments, effector and target cells were separated by a 0.45-micron filter. Parasite viability was assessed a) in vivo by injection of mice and quantitative detection of parasites by RIA or b) in vitro by the incorporation of 3H amino acids into parasite proteins. Activated macrophages killed target PE in a dose-dependent manner by elaborating a membrane-permeable soluble factor(s). The addition of small amounts of immune serum augmented the killing of the parasites. LK-activated macrophages underwent an oxidative burst upon the phagocytosis of PE as evidenced by the accumulation of reduced formazan in the NBT assay. The magnitude of the oxidative response corresponded to the number of parasites that were ingested. The phagocytosis-induced oxidative burst was necessary for subsequent killing of Plasmodium. Parasites incubated in microchambers separated from macrophages by a 0.45-micron filter were susceptible to H2O2 released by LK-activated macrophages incubated with PMA, opsonized zymosan, or P. yoelii antigen. Inhibition of protein synthesis by parasites exposed to products of activated macrophages was abrogated by preincubating macrophages with catalase but not with SOD, mannitol, or histidine. These results suggest that phagocytosis-associated oxidative mechanisms mediate the destruction of the malaria parasite. Hence, cell-mediated as well as antibody-dependent mechanisms cooperate in the immune response against malaria.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D007700:Kinetics; D008222:Lymphokines / Q000502:physiology; D008262:Macrophage Activation; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008815:Mice, Inbred Strains; D009580:Nitroblue Tetrazolium; D010587:Phagocytosis; D010961:Plasmodium / Q000254:growth & development / Q000378:metabolism
D000596:Amino Acids; D007106:Immune Sera; D008222:Lymphokines; D009580:Nitroblue Tetrazolium; D006861:Hydrogen Peroxide; D002374:Catalase