Glutathione-dependent peroxidative metabolism in the alveolar macrophage.

Phagocytosis by rabbit alveolar macrophages (AM) is accompanied by increases in O(2) consumption, glucose oxidation, and H(2)O(2) formation. Two aspects of the interrelations between these metabolic features of phagocytosis have been studied.First, the following evidence indicates that glutathione, glutathione reductase, and peroxidase serve as a cytoplasmic shuttle between H(2)O(2) and NADPH-dependent glucose oxidation: (a) AM contain 5.9 mmumoles of reduced glutathione per 10(6) cells and exhibit glutathione peroxidase and NADPH-specific glutathione reductase activity; (b) oxidized glutathione potentiates NADP stimulation of glucose oxidation; (c) an artificial H(2)O(2)-generating system stimulates glucose oxidation; (d) the cell penetrating thiol inhibitor, N-ethylmaleimide diminishes glucose oxidation. This effect largely depends on inhibition of the glutathione system rather than on inhibition of either H(2)O(2) formation or enzymes directly subserving glucose oxidation.Second, three potential H(2)O(2)-generating oxidases have been sought. No cyanide-insensitive NADH or NADPH oxidase activity could be detected. D-amino acid oxidase activity was 0.48 +/-0.07 U/10(6) cells with D-alanine as substrate.