Abstract • 165

Monocytes and macrophages are relatively long-lived cells even though they function as phagocytes in all sites and thereby expose themselves to oxidants produced in the respiratory burst (RB). We have explored mechanisms of protection against oxidant stress in monocytes beyond the enzymatic processes described for all cells (catalase, SOD, glutathione (GSH) cycle). We have found that stimulation of the RB induces the covalent bonding of thiols, especially GSH, to sulfhydryl groups on proteins (S-thiolation). The GSH is removed enzymatically as oxidant stress declines, thus offering a redox buffering that can protect against irreversible changes (denaturation). We have found also that stimulation of the RB induces the rapid transport of GSH into monocytes to levels 10-fold greater than those at baseline. Transport occurs via a specific, peroxide-sensitive GSH transporter like that of hepatocytes. At least half of the transported GSH attaches to intracellular proteins. Up-regulated GSH transport into the cell and thiolation of sensitive sulfhydryl groups have the potential to protect phagocytes (and other cells) against oxidant damage.