On the interactions between macrophages and developmental stages of Schistosoma mansoni: the cytotoxic mechanisms involved in macrophage-mediated killing of schistosomula in vitro.
In an in vitro cytotoxicity assay, mouse adherent peritoneal exudate macrophages (APEM), harvested 8-10 weeks post Schistosoma mansoni infection caused sizable (greater than 90%) specific killing of schistosomula. This cidal effect was not diminished by the addition of scavengers of oxidative burst products to the cytotoxicity assay, albeit macrophages from schistosome-infected mice produced more H2O2 than did macrophages from non-infected mice. Of inhibitors of lysosomal enzyme function and release added to the cytotoxicity assay, trypan blue (1 mg/ml) fully abolished the schistosomulicidal effect; hydrocortisone (100 micrograms/ml) was partly effective, and gold salts (1 mg/ml) were ineffective. A cidal effect was not apparent in the absence of L-arginine nor in the presence of excess (greater than 400 micrograms/ml) L-arginine, L-lysine or L-ornithine. Arginase (5 U/ml) totally abrogated the schistosomulicidal effect. The findings suggest that a macrophage protein of a lysosomal origin, dependent on arginine for its reaction and/or production, may be involved in the in vitro killing of schistosomula by macrophages from S. mansoni-infected mice.
Malkin
R
R
Department of Human Microbiology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Flescher
E
E
Lengy
J
J
Keisari
Y
Y
D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D001120:Arginine; D006861:Hydrogen Peroxide