Leishmanicidal mechanisms of human polymorphonuclear phagocytes.

Abstract

Human phagocytes isolated from peripheral blood were infected in vitro with Leishmania donovani amastogotes derived from infected hamster spleens. Phagocytosis of the parasites occurred without specific opsonization and the phagocytic efficiency of various cell types was in the order: neutrophil greater than monocyte greater than eosinophil. Light and electron microscopy showed that amastigotes were often degraded by polymorphonuclear phagocytes, but not by monocytes. Ultrastructural cytochemistry for lysosomal enzymes indicated lysosomephagosome fusion after the intracellular entry of the parasites. Reaction products for H2O2 were also detected in parasitophorous vacuoles of all cell types. Exposure of amastigotes to polymorphonuclear phagocytes at 37 degree C resulted in fewer promastigotes emerging subsequently at 27 degree C than in controls without phagocytes. By the same assay method, polymorphonuclear phagocytes from patients with chronic granulomatous disease showed limited leishmanicidal activity. A mixture of phagocyte enzyme extract, H2O2 and Cl-, Br- or I- at pH 5 showed leishmanicidal activity. The leishmanicidal mechanisms of these cells are, thus, attributable to their myeloperoxidase-H2O2-halide microbicidal system and oxygen metabolites generated by the phagocytosis-induced respiratory burst. A lower level of these microbicidal activities associated with monocytes may account for the ability of amastigotes to survive in these cells.