Human Neutrophil-Mediated Killing of Schistosomula of Schistosoma Mansoni: Augmentation by Schistosomal Binding of Eosinophil Peroxidase *

Abstract

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.

Enhanced Killing of Acanthamoeba Cysts with a Plant Peroxidase-Hydrogen Peroxide-Halide Antimicrobial System

“…This is in accordance with other studies, which have shown that I Ϫ is the most effective halide, followed by Br Ϫ and then Cl Ϫ (11,13,15). We also found that the enzyme SBP could replace HRP in the system with comparable cysticidal enhancing activity.…”

“…This resulted in an increased rate of cysticidal activity and total killing of the cyst inocula by 2 h with 3% H 2 O 2 and by 4 h with 2% H 2 O 2 . The system also enabled a sublethal H 2 O 2 concentration (1%) to produce 3-log killing within 6 h. Furthermore, this finding indicates that the previously observed in vitro activity of the peroxidase-peroxide-halide system against pathogenic viruses, bacteria, fungi, and the helminth S. mansoni can be extended to include the pathogenic protozoan Acanthamoeba (10,11,13,15,16,24,28).…”

“…Subsequently, it was demonstrated that this mechanism can be reproduced in vitro to obtain enhanced hydrogen peroxide killing of a variety of pathogenic microbes, including bacteria (10,13,15,24,25), fungi (28), human immunodeficiency virus type 1 (16), and the parasitic helminth Schistosoma mansoni (11). Peroxidases other than myeloperoxidase have been used, including eosinophil peroxidase (27), lactoperoxidase, horseradish peroxidase (HRP), and catalase (2,3,9,24).…”

“…Peroxidases other than myeloperoxidase have been used, including eosinophil peroxidase (27), lactoperoxidase, horseradish peroxidase (HRP), and catalase (2,3,9,24). In addition, bromide and iodide have been shown to be capable of replacing chloride in the reaction (9,11,15). Until now, the effects of this potent antimicrobial system on protozoans have not been reported.…”

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part I)

“…Toxic properties by intact neutrophils and macrophages are considerably increased when eosinophil-derived EPO is bound to the target cell surface, presumably due to a more sufficient utilization of H 2 O 2 by the phagocytes [259]. This has been shown by the efficacy of macrophages in killing staphylococci [260], toxoplasma [261], and trypanosoma [262] as well as for macrophage-mediated cytolysis of neoplastic cells in vitro [263].…”