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 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.
Cohen
M D
MD
Department of Environmental Medicine, New York University Medical Center, Tuxedo 10987, USA.
McManus
T P
TP
Yang
Z
Z
Qu
Q
Q
Schlesinger
R B
RB
Zelikoff
J T
JT
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D017471:Receptors, Interferon / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013696:Temperature; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000633:toxicity*; D017968:Vanadium Compounds / Q000633:toxicity*; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D002118:Calcium; D006861:Hydrogen Peroxide; D007371:Interferon-gamma; D017471:Receptors, Interferon; D013481:Superoxides; D014638:Vanadates; D017968:Vanadium Compounds; D000096743:Interferon gamma Receptor; C066075:vanadium pentoxide