Abstract

Several episodes of neutropenia were observed in a child with glutathione synthetase deficiency (5-oxoprolinuria). Studies of the patient's glutathione-deficient neutrophils were undertaken to examine the responses of the cells to oxidative stress associated with phagocytosis. The patient's neutrophils contained 10--20% of normal glutathione content. Circulating neutrophils in infection-free periods appeared less mature than normal by morphologic criteria, suggesting increased cell turnover. The cells ingested particles, responded to chemotactic stimuli, and oxidized 1-14C glucose normally. However, following ingestion of particles, the cells accumulated excess hydrogen peroxide compared with normal cells, and showed impaired protein iodination and bacterial killing. Electron micrographs revealed damage to microtubules and membranous structures in the patient's neutrophils during phagocytosis. The level of glutathione in the cells appears inadequate to protect against peroxide generated during normal cell function, and the cells are thus damaged and rendered less effective in bacterial killing. The data provide evidence for a protective role of glutathione in normal neutrophil function.