Human neutrophil-mediated killing of schistosomula of Schistosoma mansoni: augmentation by schistosomal binding of eosinophil peroxidase.
Eosinophil peroxidase (EPO) is a major component of the large cytoplasmic granules of eosinophils, and is released onto the surface of schistosomula when eosinophils adhere to antibody and complement coated organisms. EPO is a strongly cationic protein, which can bind to the surface of schistosomula with retention of peroxidatic activity. The binding per se was not toxic to the organisms under our conditions, but EPO-coated schistosomula were rapidly killed when H2O2 and halide were added, under conditions in which uncoated schistosomula were unaffected. The toxicity of the surface-bound EPO system was not significantly inhibited by albumin (20 mg/ml), in contrast to the complete inhibition by this concentration of protein when the EPO was free in solution. Purified polymorphonuclear leukocytes (PMNs) from normal donors were toxic to uncoated schistosomula in medium containing antischistosomal antibody and complement, and this toxicity was significantly increased when EPO was bound to the surface of the organisms. The toxicity of PMNs to EPO-coated schistosomula was inhibited but not abolished by the hemeprotein inhibitor azide. This is compatible with the involvement of surface-bound EPO in an enzymatic attack on the organism, utilizing H2O2 generated by PMNs stimulated by adherence to antibody and complement-coated schistosomula. PMN adherence to schistosomula is increased by surface-bound EPO, and this also may contribute to the enhancement of neutrophil-mediated toxicity by EPO. These findings indicate a mechanism by which two inflammatory cells, the eosinophil and neutrophil, may interact to enhance the destruction of a target organism.
D000818:Animals; D000906:Antibodies / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000201:enzymology*; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D010544:Peroxidases / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D047209:Eosinophil Peroxidase; D010544:Peroxidases