THE S-OXALIN, N-ACETYL-S-OXALYLCYSTEAMINE, INHIBITS LYMPHOCYTE-PROLIFERATION, IL-2 PRODUCTION AND UTILIZATION

S-Oxalins are a recently described class of cell metabolites that appe ar to function as negative regulators of proliferation. Previously we have shown that exogenous S-oxalylglutathione (GS-Ox) inhibits the pro liferation of lymphocytes by inhibiting the production and utilization of IL-2. In the present study the synthetic S-oxalin, N-acetyl-S-oxal ylcysteamine (ACS-Ox), was utilized in similar experiments to determin e whether GS-Ox itself, or possibly some metabolite formed following i nitial conversion of GS-Ox by gamma-glutamyltransferase (GGT), is resp onsible for the effects (ACS-Ox is not metabolized by GGT). ACS-Ox inh ibited DNA synthesis in lymphocytes stimulated by concanavalin A simil arly to GS-Ox. IL-2 production and utilization and IL-2R expression we re inhibited as well. ACS-Ox also inhibited the proliferation of IL-2 dependent cells at the same concentration as GS-Ox. Because the effect s of GS-Ox and ACS-Ox are so similar, presumably the S-oxalin itself, rather than some metabolite, is responsible for the observed effects. Transfer of oxalyl groups from S-oxalins to various protein thiols is the most likely mechanism involved. (C) 1996 Academic Press, Inc.