Vanadium-induced alterations in macrophage responses to biological response modifiers in vitro.
Cohen MD; Schlesinger RB; Zelikoff LT
Toxicologist 1993 Mar; 13(1):422
Previous in vivo studies have demonstrated that vanadium impairs host resistance overall, and the antimicrobial activity and function of several intracellular enzymes of macrophages (M+). To determine if the observed immunomodulation might be a result of altered interactions of M, with biological response modifiers, the release/activity of two major cytokines and the production of reactive oxygen intermediates after stimulation of vanadium-treated cultured mouse WEHI-3 M, with lipopolysaccharide (LPS) or interferon-y (IFNy) were assessed. In addition, the binding affinity and numbers of lFNy surface receptors were quantitated. Results demonstrate that the levels and activities of LPS-induced interleukin-l and tumor necrosis factor-a were decreased as vanadium concentrations increased. After treatment of cells with IFNy for 48 hr, hydrogen peroxide (H202) formation in metal-free M, increased - 40% while vanadium-treated cells had decreased H202 formation; similar effects upon superoxide anion formation were also observed. Binding studies indicated that the vanadium-treated M+ had - 500/0 fewer IFNy surface receptors, but the binding affinity of the remaining receptors were 100-400 times greater than those on control M+. This study shows that in vitro exposure to vanadium can alter M-mediated immune responses by modifying their interactions with bioactivating agents. This inability to bind and respond to these external signals could contribute to the overall diminution of host immunocompetence observed in vivo.
Vanadium-compounds; Biological-factors; In-vitro-studies; In-vivo-studies; Bioactivation
Other Occupational Concerns
The Toxicologist. Society of Toxicology 32nd Annual Meeting, March 14-18, 1993, New Orleans, Louisiana
New York University, New York, New York