Basal and Interferon-Induced 2′,5′-01igoadenylate Synthetase in Human Monocytes, Lymphocytes, and Peritoneal Macrophages

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Abstract
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-β 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-γ was less effective in inducing 2-5A synthetase than IFN-β, yielding up to 2.6-fold increases in monocytes and slight increases in lymphocytes in vitro. IFN-β also had greater 2-5A synthetase-inducing activity than IFN-γ 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-α (TNF-α) 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.