Divalent metal requirement for soluble immune response suppressor (SIRS) activity.
Soluble immune response suppressor (SIRS) is an immunosuppressive protein which requires activation to SIRSox by peroxide. This observation suggested that SIRS could be a metalloprotein. To investigate this possibility, purified hybridoma-derived SIRS was treated with chelating agents and dialyzed prior to activation with H2O2. EDTA, EGTA, or desferrioxamine prevented suppression of murine plaque-forming cell responses by SIRSox, whereas sodium citrate and penicillamine did not inhibit suppression. Suppressive activity was reconstituted by subsequent treatment of SIRS with FeSO4 (0.5 microM), NiSO4 (500 microM), or MgSO4 (500 microM), but not by FeCl3, MnSO4, CuSO4, ZnSO4, CaCl2, or CrCl3. Reconstitution of activity occurred only if FeSO4 was added at least 3 hr prior to treatment with H2O2. These data indicate that SIRS requires a divalent metal ion, probably ferrous iron, for activity, and suggest that SIRS is a metalloprotein.
Schnaper
H W
HW
Department of Pathology, Jewish Hospital, St. Louis, Missouri 63110.
D000818:Animals; D002413:Cations, Divalent / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008667:Metalloproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D013491:Suppressor Factors, Immunologic / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
D002413:Cations, Divalent; D002614:Chelating Agents; D008667:Metalloproteins; D013491:Suppressor Factors, Immunologic; C013256:soluble immune response suppressor; D006861:Hydrogen Peroxide