Basal and interferon-induced 2',5'-oligoadenylate synthetase in human monocytes, lymphocytes, and peritoneal macrophages.
2',5'-Oligoadenylate (2-5A) synthetase is an intracellular enzyme induced during viral diseases and after clinical administration of interferons (IFN). Because monocytes and T and B lymphocytes in peripheral blood are targets of viral infection, we compared the basal levels and induction of 2-5A synthetase activity in these three cell types. IFN-beta induced significant, three- to eightfold increases in 2-5A synthetase activity in monocytes and T and B lymphocytes, both in vitro and in vivo. IFN-gamma was less effective in inducing 2-5A synthetase than IFN-beta, yielding up to 2.6-fold increases in monocytes and slight increases in lymphocytes in vitro. IFN-beta also had greater 2-5A synthetase-inducing activity than IFN-gamma in HL-60 and U937 monocytic cell lines and in human peritoneal macrophages. Baseline levels of 2-5A synthetase in untreated peripheral blood monocytes separated by adherence or density gradients were three- to fivefold higher than in lymphocytes. 2-5A synthetase levels were twofold higher in B than in T lymphocytes separated by fluorescence-activated cell sorting. Tumor necrosis factor-alpha (TNF-alpha) did not induce this enzyme in peripheral blood mononuclear cells (PBMCs) or peritoneal macrophages. Thus, monocytes had greater basal and induced levels of 2-5A synthetase activity than did lymphocytes and contributed disproportionately to total 2-5A synthetase activity in peripheral blood.
Witt
P L
PL
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Spear
G T
GT
Helgeson
D O
DO
Lindstrom
M J
MJ
Smalley
R V
RV
Borden
E C
EC
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D002469:Cell Separation; D004790:Enzyme Induction; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D010529:Peritoneal Cavity / Q000166:cytology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase; D000068556:Interferon beta-1a