Interferon-γ (IFN-γ) has potent antiproliferative effects on the endothelium, although the specific mechanisms responsible for this effect are not clear. We tested the hypothesis that suppression of endothelial cell proliferation by IFN-γ is mediated by an increase in xanthine oxidase-derived O2. Human umbilical vein endothelial cells (HUVEC) were exposed to recombinant human IFN-γ. We found that [3H]thymidine uptake decreased (p < 0.05) with increasing doses of IFN-γ. Treatment of HUVEC with the xanthine oxidase inhibitor allopurinol or the O2 scavenger Superoxide dismutase had no effect (p > 0.05) on [3H]thymidine uptake of IFN-γ-treated cells. In parallel, IFN-γ decreased (p < 0.05) HUVEC cell counts, while allopurinol again had no effect (p > 0.05) on cell counts of IFN-γ-treated or control HUVEC. In addition, xanthine oxidase activity of HUVEC did not (p > 0.05) increase following treatment with IFN-γ. We conclude that IFN-γ suppresses HUVEC proliferation by a mechanism independent of O2 production by xanthine oxidase.
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