Antibody-dependent eosinophil-mediated damage to schistosomula of Schistosoma mansoni: lack of requirement for oxidative metabolism.

Abstract A larval form of Schistosoma mansoni, the schisto-somulum, is killed by human eosinophils in the presence of specific antibody. The mechanism of damage has been studied in experiments involving either unpurified normal human leukocytes or purified eosinophils and neutrophils. The addition of catalase or superoxide dismutase did not inhibit damage of schistosomula measured morphologically or by 51Cr release. In a cellfree system, hydrogen peroxide generated by glucose and glucose oxidase caused morphologically detectable damage to schistosomula. However, no evidence for action of the peroxidase system in selective eosinophil-mediated damage was found in experiments involving the incorporation of iodide into a protein bound form as a measure of peroxidase system activity. Superoxide anion production, stimulated by the presence of antibody-coated schistosomula, was approximately 10% of that induced by the addition of the soluble membrane stimulant, phorbal myristate acetate, and no differences were observed between eosinophils and neutrophils. Under completely anaerobic conditions, eosinophils were still capable of efficiently killing antibody-coated schistosomula. Under anaerobic conditions after 22 hr of incubation, 48.3 ± 5.1% (4) of the schistosomula were killed compared with 54.1 ± 9.2% (4) under aerobic conditions. Neutrophils failed to kill antibody-coated schistosomula under aerobic or anaerobic conditions. These studies demonstrate that oxidative metabolism is not required for eosinophil-mediated antibody-dependent damage to schistosomula. They provide further support for the hypothesis that degranulation and the subsequent release of major basic protein is a major mechanism of eosinophil-mediated antibody-dependent killing.