Protection of phagocytic leukocytes by endogenous glutathione: studies in a family with glutathione reductase deficiency

The significance of the glutathione redox system in phagocytic Ieukocytes was studied in a family with glutathione reductase deficiency.The polymorphonuclear leukocytes and monocytes of all 3 children in this family contained 10 % -15 % of normal glutathione reductase activity; the parents' cells showed about half the normal activity.Chemotaxis toward casein, phagocytosis of Staphylococcus aureus.DNA-anti-DNA complexes.and zymosan particles, as well as release of Iysosomal enzymes during phagocytosis, were normal in the glutathione-reductase-deficient cells.At high ratios of S. aureus to glutathione-reductase-deficient neutrophils the killing in vitro of these bacteria was slightly depressed.The metabolic response of the glutathione-reductase-deficient neutrophils during phagocytosis showed characte tistic abnormalities.During the first 5-10 mm normal oxygen consumption, hydrogen peroxide generation, and zymosan iodination were observed; thereafter these reactions stopped completely.The production of 14C02 from glucose-i -14C took place at a half-normal rate from the start of phagocytosis and stopped after about 10 mm.The same aberration in H202 formation as found in the neutrophils was also observed in the homozygous-deficient monocytes.The heterozygous neutrophils did not show this abnormality.The level of reduced glutathione in the homozygousdeficient granulocytes decreased faster during phagocytosis and reached a lower level than in normal cells.This effect was particularly pronounced when catalase and myeloperoxidase were inhibited by azide.