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

Mouse WEHI-3 cells were exposed overnight to vanadium [V; ammonium metavanadate (NH4VO3) or vanadium pentoxide (V2O5)] to determine whether documented V-induced immunomodulation might arise from altered macrophage (M-psi) interactions with interferon-gamma (IFN-gamma) or altered IFN-gamma-inducible responses. Binding studies performed at 22-degrees C indicated that although NH4VO3-pretreated cells had approximate to 48% fewer actively binding Class I IFN-gamma 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 IFN-gamma-receptor complex internalization was unaffected by V pretreatment. Spontaneous production of both hydrogen peroxide and superoxide anion was significantly increased increased by treatment with both V compounds. Total hydrogen peroxide and superoxide production was increased by stimulation of IFN-primed cells with zymosan, but relative increases in primed V-treated cells were lower than that in controls. Vanadium-trated cells also displayed decreased rates of IFN-gamma-induced changes in [Ca2+](i) levels. Although V-treated cells did not display significant increases in I-A expression after IFN-gamma 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 alteration in M-phi-mediated functions, in part, by modifying cell interactions with IFN-gamma and subsequent IFN-gamma-dependent functional parameters.