Related Experiment Videos
Reactive oxygen and nitrogen intermediates and products from polyamine degradation are Babesiacidal in vitro
W C Johnson1, C W Cluff, W L Goff
1Animal Disease Research Unit, USDA-ARS, Pullman, Washington 99164-7030, USA.
Abstract:
Products released from activated macrophages have been demonstrated to have microbicidal activity against a variety of microorganisms. Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) have been shown to affect the induction of degenerate (crisis) forms of Plasmodium spp. Polyamines are degraded into acrolein which has also been shown to be toxic to Plasmodium spp. We have investigated the possibility that these products act similarly with Babesia bovis. Crisis forms of B. bovis developed in erythrocyte cultures after the introduction of supernatants containing ROI, RNI, and acrolein. Xanthine degradation by xanthine oxidase leads to the formation of superoxide anion, hydrogen peroxide, and hydroxyl radicals. The degradation in the presence of B. bovis was toxic to the parasite. The toxicity was partially reversed by the addition of the ROI scavenger catalase. However, H2O2 added directly had little effect, suggesting a role for the other ROI products. Spermine degradation by polyamine oxidase and direct addition of acrolein was toxic in a dose-dependent manner. Finally, spontaneous generation of nitric oxide from sodium nitroprusside or S-nitroso-N-acetyl-penicillamine was also toxic in a dose-dependent manner. These data lead us to suggest a role for activated macrophages in the primary immune response against B. bovis.
Insights
Activated macrophages release products like reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) that are toxic to Babesia bovis. These findings suggest a role for macrophages in the primary immune response against this parasite.
Area of Science:
- Immunology
- Parasitology
- Biochemistry
Background:
- Activated macrophages produce microbicidal substances.
- Reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI), and acrolein exhibit toxicity against Plasmodium spp.
- The mechanisms of macrophage-mediated immunity against Babesia bovis are not fully understood.
Purpose of the Study:
- To investigate if ROI, RNI, and acrolein, products of activated macrophages, are toxic to Babesia bovis.
- To explore the role of these macrophage-derived products in the immune response against B. bovis.
Main Methods:
- Cultured Babesia bovis-infected erythrocytes were exposed to supernatants containing ROI, RNI, and acrolein.
- Xanthine degradation by xanthine oxidase was used to generate ROI.
- Spermine degradation and direct acrolein addition were employed to assess toxicity.
- Nitric oxide generation from sodium nitroprusside and S-nitroso-N-acetyl-penicillamine was studied.
Main Results:
- Introduction of ROI, RNI, and acrolein induced crisis forms of B. bovis in erythrocyte cultures.
- Xanthine degradation products were toxic to B. bovis, with toxicity partially reversed by catalase, indicating a role for ROI other than H2O2.
- Spermine degradation and acrolein were dose-dependently toxic to the parasite.
- Nitric oxide also exhibited dose-dependent toxicity.
Conclusions:
- Reactive oxygen intermediates, reactive nitrogen intermediates, and acrolein are toxic to Babesia bovis.
- These findings suggest that activated macrophages play a role in the primary immune defense against B. bovis infections.