Project Summary (1995-2000)

This project investigates the interaction and mechanism of vanadium with lung tissue that gives rise to significant physiological effects. Vanadium is a Superfund target metal known to have toxic health effects, and found at Superfund sites. Inhalation is a frequent route of entry into the human body. The ultimate chemical species of vanadium to enter cells relates to its chemical form in environmental particles as well as the fluid media encountered in tissues. Two important adverse responses in the lung related to vanadium exposure are the generation of active oxygen metabolites and the induction of pro-inflammatory cytokines. These events occur in pulmonary alveolar macrophages (PAMs) which play a central role in the protection of the lung and the development of pulmonary disease. Specific aims of these studies include definition of the dissolution patterns and chemical forms of vanadium compounds in the lung, and dose determination of vanadium compounds in intracellular compartments of PAMs and other lung cells. Mechanisms by which these compounds produce massive increases in active oxygen metabolites and induce pro-inflammatory cytokines is also being studied. Finally, mechanisms of toxicity in human PAMs obtained by bronchoalveolar lavage from workers occupationally exposed to vanadium compounds and non-smoking, non-exposed human volunteers are assessed. The coordination of this research with that of Project 5 allows scientists to directly correlate the mechanistic findings with an in vivo human exposure situation.