XANTHINE-OXIDASE DOES NOT MEDIATE THE ANTIPROLIFERATIVE EFFECTS OF INTERFERON-GAMMA IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

Interferon-gamma (IFN-gamma) has potent antiproliferative effects on t he endothelium, although the specific mechanisms responsible for this effect are not clear. We tested the hypothesis that suppression of end othelial cell proliferation by IFN-gamma is mediated by an increase in xanthine oxidase-derived O-2(radical-anion). Human umbilical vein end othelial cells (HUVEC) were exposed to recombinant human IFN-gamma. We found that [H-3]thymidine uptake decreased (p < 0.05) with increasing doses of IFN-gamma. Treatment of HUVEC with the xanthine oxidase inhi bitor allopurinol or the O-2(radical-anion) scavenger superoxide dismu tase had no effect (p > 0.05) on [H-3]thymidine uptake of IFN-gamma-tr eated cells. In parallel, IFN-gamma decreased (p < 0.05) HUVEC cell co unts, while allopurinol again had no effect (p > 0.05) on cell counts of IFN-gamma-treated or control HUVEC. In addition, xanthine oxidase a ctivity of HUVEC did not (p > 0.05) increase following treatment with IFN-gamma. We conclude that IFN-gamma suppresses HUVEC proliferation b y a mechanism independent of O-2(radical-anion) production by xanthine oxidase.