Faculty Bibliography

Male Fisher 344 rats were exposed to 2 mg vanadium(V)/m3 (as ammonium metavanadate NH4VO3, 0.32 micron MMD) atmospheres for 8 hr/day for 4 days in a nose-only exposure system. In exposed rats, lung V burdens increased in a time-dependent fashion. Analysis of lung cells and lavage fluid 24 hr after the final exposure suggested that tissue damage and a strong inflammatory response was elicited; numbers of neutrophil and small macrophages (Mo), as well as levels of lavageable protein and lactate dehydrogenase, were significantly elevated as compared with levels observed with air-exposed rats. Vanadium also affected pulmonary alveolar Mo (PAM) capacities to produce and respond to immunoregulating cytokines. Inducible PAM production of tumor necrosis factor-alpha was significantly inhibited, as was the ability to increase cell surface Class II/I-A molecule expression in response to interferon-gamma (IFN gamma). PAM from V-exposed hosts were also inhibited in their ability to be primed by IFN gamma to produce superoxide anion and hydrogen peroxide in response to stimulation with opsonized zymosan. These studies indicate that short-term repeated exposure of rats to atmospheric V, at levels encountered in an occupational setting, can alter host pulmonary immunomocompetence, with one major effect occurring at the level of cytokine-related functions. These alterations may be underlying mechanisms for the well-documented increases in bronchopulmonary infections and cancers in workers chronically exposed to V-containing atmospheres

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

The evolutionary aspects of immunoregulation and the immunotoxic effects of xenobiotics in species ranging from humans to marine invertebrates were discussed at a recent meeting. This report describes progress in our understanding of this fascinating field