Vanadium alters macrophage interferon-y-interactions and -inducible responses.
Cohen-MD; McManus-TP; Yang-Z; Qu-Q; Zelikoff-JT; Schlesinger-RB
Toxicologist 1995 Mar; 15(1):257
Vanadium (V) impairs host resistance overall, and the antimicrobial activity and function of several intracellular enzymes of macrophages (M) in particular. Mouse WEHI-3 M-like cells were exposed overnight to subcytotoxic concentrations of ammonium metavanadate (NH4 VO3) to determine whether this observed immunomodulation might be due, at least in part, to altered M-interactions with interferon-y (IFNy) or IFNy-inducible responses, i.e., increased reactive oxygen intermediate (ROI) production, Ca2+ ion influx, and surface Class II/Ia antigen expression. Binding studies performed at 22°C indicated that V -treated cells had =50% fewer actively-binding receptors, but binding affinities 450-times greater than that of control receptors. At 4°c, V-treated cells had 98% fewer functional receptors, but again higher (145-fold) affinities. IFNy-receptor complex internalization was unaffected by V, although significantly higher in cells incubated at temperatures which minimize uptake. ROI production in IFNy-stimulated V-treated (either NH4 V03 or V 2 O5 [vanadium pentoxide]) cells was decreased relative to spontaneous production, while control cells showed consistent increases due to IFNy priming. Vanadium also reduced the Ca2+ ion influx rate into stimulated cells without affecting final cell Ca2+ burdens. Although V did not affect IFNy-induced Ia expression, exposures resulted in increased numbers of Ia-bearing cells with lower maximal antigen densities than control cells. The results of this study show that V exposure may alter M-mediated functions by modifying cell interactions with IFNy and subsequent IFNy-dependent parameters.
Vanadium-compounds; Ammonium-compounds; Laboratory-animals; Animals; Animal-studies; Lung-disorders; Pulmonary-system-disorders; Respiratory-system-disorders
Other Occupational Concerns
The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland
New York University, New York, New York