NITRIC-OXIDE MEDIATES THE MICROBICIDAL ACTIVITY OF EOSINOPHILS

There are several experimental evidences that nitric oxide (NO) is inv olved in the microbicidal activity of macrophages against a number of intracellular pathogens including Leishmania major, Trypanozoma cruzi, Toxoplasma gondii It is also well known that eosinophils (EO) have mi crobicidal activity against many parasites such as Schistosoma mansoni , Trichinella spiralis, T. cruzi and L. amazonensis. The purpose of th is study was to investigate if NO is involved in the microbicidal acti vity of EO against L. major. Eosinophils harvested from peritoneal cav ity of rats released spontaneously after 24 and 48 hr a small amount o f nitrite. This release was enhanced by the treatment of cells with IF N-gamma (200 IU/ml). This release was blocked by addition of the NO sy nthase inhibitor L-NIO (100 mu M) into the culture. To determinate the leishmanicidal activity of eosinophils the parasites were incubated w ith activated eosinophils with IFN-gamma and the ability of surviving parasites to incorporate [H-3]thymidine was evaluated. IFN-gamma-activ ated eosinophils were able to kill L. major and to release high levels of nitrite. The ability to destroy L. major and the release of NO wer e completely blocked by L-NIO. These results indicate that activated e osinophils release NO which is involved in the microbicidal activity o f these cells against L. major.