Role of granulocyte oxygen products in damage of Schistosoma mansoni eggs in vitro.

Abstract

The objectives of this study were to describe the ultrastructure of granulocyte-Schistosoma mansoni egg interaction and to determine the role of reduced oxygen products as effectors of cell-mediated damage to the parasite target. Granulocytes attached to the parasites and closely applied their plasma membranes to the microspicules of the egg shell 30 min after mixing in the presence of immune serum. By 4 h, the egg shell was fractured and granulocyte pseudopodia extended toward the underlying miracidium. Granulocyte attachment to eggs resulted in release of O-(030-0.52 nmol/min per 2 X 106 cells) and accumulation of H202 (0.14-0.15 nmol/min) in the presence of antibody or complement. Granulocytes reduced egg tricarboxylic-acid cycle activity and hatching by 283±0.9 and 35.2±2.8%, respectively (cell-egg ratio of 1,000: 1). Exogenous superoxide dismutase (10 M&g/ml) inhibited granulocyte toxicity for egg metabolic activity (3.0±2.1% reduction in acetate metabolism vs. 283±0.9% decrease in controls without superoxide dismutase, P < 0.0005) and hatching (12.5±1.8% reduction, P < 0.0005), whereas catalase and heparin had no effect. Inhibitors of myeloperoxidase (1 mM azide, cyanide, and methimazole) augmented granulocyte-mediated toxicity of egg tricarboxylic-acid cycle activity (44-58% reduction in activity vs. 31 and 35% reduction in controls), suggesting that H202 released from cells was degraded before reaching the target miracidium. Oxidants generated by acetaldehyde (2 mM)-xanthine oxidase (10 mU/ml) also decreased egg metabolic activity and hatching by 62.0±9.0 and 38.7±73%, respectively. Egg damage by the cell-free system was partially prevented by superoxide dismutase (26.5±4.2% reduction in egg tricarboxylic-acid cycle activity) and completely blocked by catalase (0% reduction in activity). These data suggest that granulocyte-mediated toxicity for S. mansoni eggs is dependent on release of 02 or related molecules. These oxygen products, unlike H202, may readily reach the target miracidium where they may be converted to H202 or other microbicidal effector molecules.

Disparate effects of interferon-gamma and tumor necrosis factor-alpha on early neutrophil respiratory burst and fungicidal responses to Candida albicans hyphae in vitro.

“…Our previous studies with unprimed PMN had established that hyphae elicited low absolute levels ofO2 release when compared to respiratory burst responses evoked by standard, nonviable stimuli, including soluble FMLP and particulate opsonized zymosan (39)(40)(41)(42). Nevertheless, responses to hyphae were in ranges reported for levels of respiratory burst activation by other types of microorganisms (59,60) and were of sufficient magnitude to mediate fungicidal activity (3)(4)(5). Our previous studies defined ratios of hyphae to PMN supporting optimal respiratory burst stimulation (39).…”

Current Status of Vaccines for Schistosomiasis

“…Granulocytes release oxygen radicals that are toxic for S. mansoni, and exogenous superoxide dismutase (SOD) inhibited granulocyte toxicity for egg metabolic activity and hatching (77). A cDNA encoding a SOD with a signal peptide was cloned from S. mansoni, and its protein product was recognized by sera from infected humans (136).…”

Biochemical Characterization of 2-Cys Peroxiredoxins from Schistosoma mansoni

“…During the life cycle of the parasite, eggs released from female worms are enveloped in an immune-generated granuloma. Neutrophils and eosinophils present in the granuloma generate high levels of reactive oxygen intermediates around the egg (43,44). Although these immune cells can eventually destroy liver-trapped eggs and are the main cause of host pathology, formation of the granuloma is, paradoxically, essential for the passage of the egg across the intestinal wall and for survival of the host (44 -47).…”