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Increased Sensitivity to H₂O₂ in Glutathione Peroxidase-Deficient Rat Granulocytes¹

The Division of Gastroenterology and Nutrition, Children's Hospital, Boston, MA 02115 Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, MA 02139 the^* Department of Pediatrics and the Cancer Center, University of Rochester Medical Center, Rochester, NY 14642

The role of glutathione peroxidase (GSH-Px) in protecting phagocytic function of peritoneal granulocytes (PMN) was assessed using selenium (Se)-deficient rats. Rats fed an Se-deficient diet for 12–15 weeks developed profound Se deficiency. Their PMN were found to contain 11% of control levels of GSH-Px. Previous studies have shown that at this level of enzyme activity, the metabolism of H₂O₂ via the glutathione cycle was impaired. Despite this, the initial rate of phagocytosis, as measured by the ingestion of opsonized oil red O particles, was normal. Prior incubation of PMN in an H₂O₂-generating system resulted in a time-dependent loss in the ability of the cells to ingest. GSH-Px-deficient PMN were affected to a greater degree than control PMN. Degranulation, as measured by the release of ß-glucuronidase into the extracellular medium after stimulation of PMN by opsonized zymosan in the presence of cytochalasin B, was unaffected by GSH-Px deficiency. Prior incubation of PMN in an H₂O₂ generating system resulted in decreased degranulation in both control and GSH-Px-deficient PMN, with GSH-Px-deficient PMN being affected to a greater degree. The killing of Staphylococcus aureus 502A by both control and GSH-Px-deficient PMN was the same. There was no effect of prior H₂O₂ incubation on bacterial killing in either control or GSH-Px-deficient PMN. Thus, GSH-Px appears to be important in protecting those aspects of phagocytic function that are sensitive to the destructive properties of exogenous H₂O₂.

KEY WORDS: • selenium deficiency • glutathione peroxidase deficiency • phagocyte function • H₂O₂ sensitivity

¹ This work was supported in part by grants from the National Institutes of Health 5T32-AM07070 from the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, and CA26506 and CA26033 from the National Cancer Institute.

² Recipient of a Research Career Development Award A100311.

Manuscript received 6 March 1984.