Mechanisms for the oxidation of reduced gluthathione by stimulated granulocytes.
We have reported previously that human granulocytes have an irreversible fall in their endogenous reduced soluble sulfhydryls following zymosan stimulation. In the present study, we demonstrate that stimulated granulocytes release one or more reactive oxygen species (ROS) with the capacity to oxidize reduced glutathione (GSH). One or more of these compounds is stable enough to be detected in the supernatant. The formation of these stable oxidants appears to require H2O2 and heme or a heme-containing enzyme. However, once formed, the compound reacts with GSH without these factors. The ROS is not superoxide or hydroxyl radical, since neither superoxide dismutase nor the hydroxyl scavengers, mannitol and benzoic acid, change the rate of the reaction. Methionine has recently been demonstrated to be oxidized to a sulfoxide by a reactive oxygen species that is dependent on H2O2 and heme for its production. We found that methionine could directly react with the same ROS that degrades GSH. The ROS also has the capacity to oxidize iodide and fix halogen to proteins. Our data indicate that stimulated granulocytes release a ROS with the capacity to oxidize GSH, react with methionine, and oxidize and fix I- to protein. The compound, therefore, appears dependent on H2O2 and the myeloperoxidase system for its production, and is either hypochlorous acid (HOCI) or a compound derived from HOCI, such as a chloramine. The capacity of GSH to react with this ROS suggests an additional role for this tripeptide in cellular protection against oxidant injury.
D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002374:Catalase / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood*; D019803:Glutathione Disulfide; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism / Q000494:pharmacology; D009895:Opsonin Proteins / Q000502:physiology; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D001565:Benzoates; D009895:Opsonin Proteins; D008353:Mannitol; D019817:Benzoic Acid; D015054:Zymosan; D008715:Methionine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D019803:Glutathione Disulfide