VANADIUM AFFECTS MACROPHAGE INTERFERON-GAMMA-BINDING AND INTERFERON-GAMMA-INDUCIBLE RESPONSES

Mouse WEHI-3 cells were exposed overnight to vanadium [V; ammonium met avanadate (NH4VO3) or vanadium pentoxide (V2O5)] to determine whether documented V-induced immunomodulation might arise from altered macroph age (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 affini ties were 1.5-fold greater than that of control cell receptors; Class II expression was unaffected but affinities were reduced 2-fold. Postb inding IFN-gamma-receptor complex internalization was unaffected by V pretreatment. Spontaneous production of both hydrogen peroxide and sup eroxide anion was significantly increased increased by treatment with both V compounds. Total hydrogen peroxide and superoxide production wa s increased by stimulation of IFN-primed cells with zymosan, but relat ive increases in primed V-treated cells were lower than that in contro ls. 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 treatm ent, increased numbers of I-A(+) cells (irrespective of priming) and l ower maximal antigen densities than observed on I-A(+) control cells w ere evident. Results from this study show that V exposure may produce alteration in M-phi-mediated functions, in part, by modifying cell int eractions with IFN-gamma and subsequent IFN-gamma-dependent functional parameters.