Plasmodium berghei resists killing by reactive oxygen species.
Reactive oxygen species (ROS) are widely believed to kill malarial parasites. C57BL/6 mice injected with P. berghei inocula incubated with supraphysiological doses of NO (< or =150 microM) or with peroxynitrite (220 microM), however, exhibited parasitemia similar to that seen with those given control inocula, and there was no difference in disease development. Only treatment of inocula with NO doses nearing saturation (> or =1.2 mM) resulted in no detectable parasitemia in the recipients; flow cytometric analysis with a vital dye (hydroethidine) indicated that 1.5 mM NO lysed the erythrocytes rather than killing the parasites. The hemoglobin level in the inocula was about 8 muM; the hemoglobin was mainly oxyhemoglobin (oxyHb) (96%), which was converted to methemoglobin (>95%) after treatment with 150 microM NO. The concentrations of 150 microM of NO and 220 microM of peroxynitrite were far in excess of the hemoglobin concentration (approximately 8 microM), and yet no parasite killing was detected. We therefore conclude that hemoglobin protects Plasmodium parasites from ROS, but the parasite likely possesses intrinsic defense mechanisms against ROS.
Sobolewski
Peter
P
La Jolla Bioengineering Institute, CA 92037, USA.
Gramaglia
Irene
I
Frangos
John A
JA
Intaglietta
Marcos
M
van der Heyde
Henri
H
D000818:Animals; D004912:Erythrocytes / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D018512:Parasitemia / Q000469:parasitology; D030421:Peroxynitrous Acid / Q000008:administration & dosage / Q000494:pharmacology; D010962:Plasmodium berghei / Q000187:drug effects* / Q000472:pathogenicity; D017382:Reactive Oxygen Species / Q000008:administration & dosage / Q000494:pharmacology*
D006454:Hemoglobins; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide