Susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to nitric oxide and hydrogen peroxide in cell-free culture and from IFN gamma-activated macrophages.
The susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to H2O2 and NO either in cell-free culture or from IFN gamma-activated macrophages was examined. In cell-free culture, O. lienalis microfilariae were highly susceptible to H2O2 induced toxicity, exhibiting rapid reductions in motility and viability. The addition of exogenous catalase abrogated H2O2-induced killing. In contrast, B. malayi microfilariae were relatively resistant to H2O2, with concentrations as high as 50 microM having no effect on motility or viability. On exposure to NO, both species showed reductions in motility within 5-30 min, but longer was required to see effects on the viability of microfilariae. Parasites incubated with IFN gamma-activated macrophages also exhibited marked reductions in motility and viability. In cultures with B. malayi and activated macrophages, inhibition of these effects was achieved by the addition of either L-NMMA, to abolish NO production, or neutralizing anti-TNF alpha antibodies. Attempts to inhibit parasite killing by the addition of catalase to macrophage cultures were ineffective. The results of this study show that B. malayi and O. lienalis microfilariae have different susceptibility to H2O2, but are equally affected by exposure to NO. Moreover both species are killed by IFN gamma-activated macrophages and in the case of B. malayi, killing is dependent on the generation of NO via TNF alpha.
Taylor
M J
MJ
Liverpool School of Tropical Medicine, UK.
Cross
H F
HF
Mohammed
A A
AA
Trees
A J
AJ
Bianco
A E
AE
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D017178:Brugia malayi / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005368:Filariasis; D005849:Gerbillinae; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000494:pharmacology*; D009573:Nitrites / Q000494:pharmacology; D009854:Onchocerca / Q000187:drug effects* / Q000502:physiology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011994:Recombinant Proteins; D026423:S-Nitroso-N-Acetylpenicillamine; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000871:Anthelmintics; D009573:Nitrites; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D002374:Catalase; D010396:Penicillamine