Title: Vanadium affects macrophage interferon-gamma-binding and -inducible responses.
Authors: Cohen, M D; McManus, T P; Yang, Z; Qu, Q; Schlesinger, R B; Zelikoff, J T
Published In Toxicol Appl Pharmacol, (1996 May)
Abstract: 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 phi) 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 approximately 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 by treatment with both V compounds. Total hydrogen peroxide and superoxide production was increased by stimulation of IFN gamma-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 IFN gamma-induced changes in [Ca2+]i levels secondary to increased resting [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 alterations in M phi-mediated functions, in part, by modifying cell interactions with IFN gamma and subsequent IFN gamma-dependent functional parameters.
PubMed ID: 8658499
MeSH Terms: Animals; Antigens, CD/metabolism; Calcium/metabolism; Hydrogen Peroxide/metabolism; Interferon Type II/metabolism*; Macrophages/drug effects*; Macrophages/metabolism; Mice; Receptors, Interferon/metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Superoxides/metabolism; Temperature; Tumor Cells, Cultured; Vanadates/toxicity*; Vanadium Compounds/toxicity*