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.
Fetsch
J
J
Institute for Pharmacy, Free University Berlin, FRG.
Maurer
H R
HR
D000818:Animals; D002417:Cattle / Q000378:metabolism*; D002455:Cell Division; D002851:Chromatography, High Pressure Liquid; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006098:Granulocytes / Q000166:cytology*; D051379:Mice; D009994:Osmolar Concentration; D013154:Spleen / Q000378:metabolism*; D014462:Ultrafiltration
D005978:Glutathione