Exposure to vanadium in the working environment as well as in the air of most metropolitan areas presents a possible immunomodulating risk to amn. Previous work in our laboratory has indicated that several aspects of immune function may be altered by vanadium exposure. Vanadium, in the form of ammonium metavanadate, was shown to be immunosuppressive in mice following 3 or 6 weeks of exposure at doses below the LD50 value. Resistance to a viable pathogen, Listeria monocytogenes, was decreased by over 250% after only 3 weeks of exposure. Peritoneal macrophage phagocytic activity was significantly depressed as a result of the vanadium treatments. Because resistance to Listeria was controlled, in part, by macrophage activity in three separate phases, the effect of vanadium on the acts of phagocytosis, intracellular killing, and the recruitment of other immune system components warranted further examination. The effects of vanadium treatment on the biochemical and structural aspects of mouse peritoneal macrophages as related to their phagocytic and bactericidal functions will be examined. Specifically, the objectives of this study are (1) to determine if vanadium exposure inhibits the phagocytosis of bacteria or modifies the bactericidal activity of the peritoneal macrophages, (2) to determine if vanadium treatment alters the macrophage enzyme activities involved in phagocytosis and intracellular killing, (3) to examine the effects of vanadium on the macrophage cytoskeleton and receptor expression, and to relate any alterations to cytoskeleton and receptor expression, and to relate any alterations to changes in phagocytic/killing abilities and (4) to evaluate the effect of vanadium on macrophage production and release of select monokines. An examination of the current literature shows an increasing interest in the biological aspects of vanadium chemistry. The information obtained in this study will contribute to the understanding of vanadium toxicity and its immunotoxicity in the body. The results may also be useful in explaining the deleterious effects of the metal observed in man following exposure. The majority of reported immunotoxicity studies are primarily based upon analysis of macrophage viability and phagocytic activity following chemical treatment of the cells or the host. This study proposes to determine an underlying mechanism of immunomodulation form an environmental pollutant, vanadium. In addition, the approach used in this can serve as a basis for detailed mechanistic studies of the immunotoxicological effects of other heavy metals of environmental pollutants.
