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Title: REACTIVE OXYGEN AND NITORGEN INTERMEDIATES AND PRODUCTS FROM POLYAMINE DEGRADATION ARE BABESIACIDAL IN VITRO

Author
item Johnson, Wendell
item Goff, Willard
item CLUFF, CHRISTOPHER - WASHINGTON STATE UNIV
item WYATT, CAROL - WASHINGTON STATE UNIV

Submitted to: Annals of the New York Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: Babesia bovis is a protozoan (one celled animal) that invades red blood cells of cattle after being transmitted through the bite of certain species of ticks. The resulting disease is of economic importance to cattle producers in the areas where the disease occurs, and to U.S. cattle producers who would benefit from increased export markets if an improved vaccine was available. Studies in our laboratory are designed to identify the immune mechanism that is induced in cattle that mount a successful immune response after exposure to the parasite. An understanding of the mechanism induced in cattle that survive will be important in the development of an improved vaccine. A particular type of white blood cell called macrophages may be involved in the early immune response to Babesia bovis infection. This cell type can release several soluble factors that might have an effect on the parasite. In this study we tested three of these factors directly for their ability to kill the parasite in culture conditions. It was found that two of the factors were efficient at killing the parasite within the red blood cells. These findings lead us to believe that macrophages may be activated early in the response to infection, and current studies will focus on this issue.

Technical 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 etoxic to Plasmodium spp. We have investigated the possibility that these products act similarly with Babesia bovis. Crisis forms of B. bovis in erythrocyte cultures developed 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 and was toxic to B. bovis and 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 was also toxic in a dose dependent manner. This data leads us to suggest a role for activated macrophages in the primary immune response against these intraerythrocytic parasites.