Hormonal and immunological regulation of 2', 5'-oligoadenylate synthetase activity in human peripheral blood mononuclear cells.
A newly developed method for assaying 2', 5'-oligoadenylate (2, 5A) synthetase activity by polyacrylamide gel electrophoresis was applied to peripheral blood mononuclear cells (PBMC) from normal subjects, HIV-positive subjects, and renal cell carcinoma (RCC) patients. Sex differences were observed in 2, 5A synthetase activity of PBMC from normal young adults, males having eightfold higher activities of this enzyme than females. Moreover, compared to values for postmenopausal (PM) females receiving estrogen replacement, untreated PM females had higher activities. Collectively, these results suggest that estrogen downregulates 2, 5A synthetase activity. Activities of 2, 5A synthetase were investigated in two disease states associated with altered immune function. In one patient with AIDS-related Kaposi's sarcoma, interferon-alpha (IFN-alpha) therapy increased 2, 5A synthetase activity twofold. In addition, combined therapy with interleukin-2 (IL-2) and IFN-alpha increased 2, 5A synthetase activities in eight of nine patients with RCC. Therefore, in patients receiving immunotherapy with IL-2 and IFN-alpha, our new assay could contribute to evaluation of immune stimulation. In general, studies in vitro confirmed these observations; however, exposure of PBMC from RCC patients revealed that in vitro IL-2 failed to induce this enzyme activity as it did in PBMC from normal volunteers.
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033.
M E
ME
Miele
E S
ES
Vesell
W C
WC
Ehmann
A
A
Lipton
H
H
Harvey
N C
NC
Kan
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000163:Acquired Immunodeficiency Syndrome / Q000201:enzymology; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes; D016827:CD8 Antigens / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000628:therapy; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000201:enzymology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D008593:Menopause / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000201:enzymology / Q000628:therapy; D012737:Sex Factors
D016827:CD8 Antigens; D004967:Estrogens; D016898:Interferon-alpha; D007376:Interleukin-2; D000255:Adenosine Triphosphate; D015088:2',5'-Oligoadenylate Synthetase