Increased sensitivity to H2O2 in glutathione peroxidase-deficient rat granulocytes.
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 beta-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.
D000818:Animals; D001770:Blood Bactericidal Activity / Q000187:drug effects; D005966:Glucuronidase / Q000097:blood; D005979:Glutathione Peroxidase / Q000172:deficiency*; D006098:Granulocytes / Q000187:drug effects / Q000201:enzymology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000172:deficiency
D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005966:Glucuronidase; D012643:Selenium