Glutathione: an in vitro granulopoiesis inhibitor at nanomolar concentration, isolated from calf spleen.

We isolated a peptide from calf spleen that specifically inhibits murine granulopoiesis in vitro. Human T-lymphocyte colony growth was not affected. Formation of erythroid colony-forming units (CFU-E) was only slightly inhibited at a concentration 1000-fold higher compared to granulocyte-macrophage colony-forming cell (GM-CFC) assay. After high performance liquid chromatography purification we isolated a monomer (reduced peptide) showing the inhibitory activity and a dimer (oxidized peptide) with stimulatory activity. The isolated peptide was identified as glutathione. The reduced form of this well-known tripeptide (GSH) specifically inhibits murine granulopoiesis in vitro at 10(-7)-10(-8) M concentration. Oxidized glutathione (GSSG) stimulates GM-CFC formation; the extent of stimulation depends on the colony-stimulating factor concentration. The striking finding that GSH and GSSG modulate granulopoiesis at nanomolar concentrations requires further studies on the molecular interaction between either peptide with GM-CSF and its receptor protein.