Role of hypochlorous acid in Trypanosoma musculi killing by phagocytes

Abstract

Trypanosoma musculi are readily killed when phagocytosed by mononuclear phagocytes but the nature of the mediators of this cytotoxicity is unclear. Among the most potent mediators are oxygen-derived species. The generation of chemiluminescence (CL) by peritoneal macrophages from 12 day T. musculi-infected mice, which phagocytose and kill parasites when opsonizing antibodies are present, was recorded in the presence of antibody-coated trypanosomes. Taurine, a specific quencher of hypochlorous acid (HOCl) inhibited CL production by peritoneal macrophages, showing that HOCl is produced during phagocytosis of T. musculi. In vitro, HOCl alone exerted a powerful trypanocidal activity which was inhibited in the presence of specific quenchers. The role of HOCl generated by phagocytes in trypanosome killing was studied using granulocytes which produce more oxygen-derived species than macrophages when stimulated. Phorbol myristate acetate-triggered granulocytes can destroy T. musculi and trypanosome killing is inhibited in the presence of taurine. These data demonstrate that HOCl produced by phagocytes can effectively destroy T. musculi.