Reticulocytes contain increased amounts of reduced glutathione except when produced by acetylphenylhydrazine

The glutathione status (GSH) of mouse and human reticulocytes in comparison with that of older cells was investigated. Reticulocytosis in mice was induced either by repeated bleeding or a single large dose of acetylphenylhydrazine (APH). Blood samples from humans were obtained from patients with a variety of acquired and inherited anemias associated with an increased reticulocyte count. The human cells were fractionated by simple centrifugation into top, middle, and bottom layers. Bled mice attained a reticulocyte count of 30% and displayed a red cell GSH content two- to threefold greater than control values. APH-Injected mice attained, in some cases, reticulocyte counts of 100% and displayed no increase in red cell GSH. CoCl₂-Induced reticulocytosis also caused a small rise in GSH. In humans, reticulocyte-rich fractions were associated with a nearly twofold increase in GSH content when compared to reticulocyte-poor bottom layers. These data confirm some previous studies of human and animal reticulocytes and contradict other investigations in the same area. Although the utility of increased GSH levels remains obscure, increased GSH may be required for protein or heme synthesis and/or as protection against oxidative stresses which exceed those found in mature red cells.