Vanadium affects macrophage interferon-γ-binding and -inducible responses

Abstract Mouse WEHI-3 cells were exposed overnight to vanadium [V; ammonium metavanadate (NH 4 VO 3 ) or vanadium pentoxide (V 2 O 5 )] to determine whether documented V-induced immunomodulation might arise from altered macrophage (Mφ) interactions with interferon-γ (IFNγ) or altered IFNγ-inducible responses. Binding studies performed at 22°C indicated that although NH 4 VO 3 -pretreated cells had ≈48% fewer actively-binding Class I IFNγ receptors, binding affinities were 1.5-fold greater than that of control cell receptors; Class II expression was unaffected but affinities were reduced 2-fold. Postbinding IFNγ–receptor complex internalization was unaffected by V pretreatment. Spontaneous production of both hydrogen peroxide and superoxide anion was significantly increased by treatment with both V compounds. Total hydrogen peroxide and superoxide production was increased by stimulation of IFNγ-primed cells with zymosan, but relative increases in primed V-treated cells were lower than that in controls. Vanadium-treated cells also displayed decreased rates of IFNγ-induced changes in [Ca 2+ ] i levels secondary to increased resting [Ca 2+ ] i levels. Although V-treated cells did not display significant increases in I-A expression after IFNγ treatment, increased numbers of I-A + cells (irrespective of priming) and lower maximal antigen densities than observed on I-A + control cells were evident. Results from this study show that V exposure may produce alterations in Mφ-mediated functions, in part, by modifying cell interactions with IFNγ and subsequent IFNγ-dependent functional parameters.