Human endothelial cells are activated by IFN-gamma to inhibit Toxoplasma gondii replication. Inhibition is due to a different mechanism from that existing in mouse macrophages and human fibroblasts.
Toxoplasma gondii invaded and proliferated in cultured human umbilical vein endothelial cells. Preincubation of the human umbilical vein endothelial cells with human rIFN-gamma induced a high degree of inhibition of T. gondii replication, with the effect being dose dependent. In order to try to elucidate the inhibitory mechanism, we tested the presence of several factors that are known to operate against intracellular parasites in other cell types. We found, by means of a competitive inhibitor, that L-arginine-dependent production of reactive nitrogen intermediates was not the cause of inhibition of T. gondii proliferation, thus contrasting with the inhibitory mechanism found in activated mouse macrophages. Furthermore, the inhibition of replication was not overcome by oxygen scavengers or by saturation of the system with tryptophan, suggesting that neither reactive oxygen intermediates nor the induction of tryptophan starvation was responsible.
Woodman
J P
JP
Unité de Recherche Université-INRA d'Immunologie Parasitaire, UFR des Sciences Pharmaceutiques de Tours, France.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000502:physiology; D011994:Recombinant Proteins; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology*; D014364:Tryptophan / Q000502:physiology; D019323:omega-N-Methylarginine
D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D014364:Tryptophan; D001120:Arginine; D010100:Oxygen