TY - JOUR
T1 - Divalent metal requirement for soluble immune response suppressor (SIRS) activity
AU - Schnaper, H. William
N1 - Funding Information:
’ Supported by USPHS Grant CA-40567 from the National Cancer Institute and Grant 2224 from the Council for Tobacco Research-U.S.A., Inc. ’ Recipient of Clinical Investigator Award DKO 131 7 from the National Institute of Diabetes, Digestive and Kidney Diseases, USPHS. Address reprint requests and correspondence to H. William Schnaper, Renal Division, St. Louis Children’s Hospital, 400 S. Kingshighway, St. Louis, MO 63 110. 3 Abbreviations used: PFC, plaque-forming cell; SIRS, soluble immune response suppressor; SIRS,,, activated SIRS.
PY - 1989/1
Y1 - 1989/1
N2 - 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 μM), NiSO4 (500 μM), or MgSO4 (500 μM), 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.
AB - 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 μM), NiSO4 (500 μM), or MgSO4 (500 μM), 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.
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U2 - 10.1016/0008-8749(89)90365-1
DO - 10.1016/0008-8749(89)90365-1
M3 - Article
C2 - 2521303
AN - SCOPUS:0024537950
SN - 0008-8749
VL - 118
SP - 157
EP - 165
JO - Cellular Immunology
JF - Cellular Immunology
IS - 1
ER -