Transition metals are components of airborne particles and have been implicated in adverse health effects. The relative inflammatory potential of these metals is usually inferred from separate studies that focus on only one or a few individual metals. Comparisons of relative potency among several metals from these separate studies can be difficult. In one comprehensive study, we measured the pulmonary effects of equimolar doses of six metals in soluble form. Our purpose was to compare inflammatory potential and pulmonary toxicity among individual transition metals. Rats received saline, 0.1 or 1.0 micromol/kg of vanadium, nickel, iron(II), copper, manganese, or zinc as sulfates. Bronchoalveolar lavage (BAL) was performed at 0, 4, 16, or 48 h postinstillation. All treatments except V showed increased lactate dehydrogenase activity in BAL fluid; Cu- and Ni-exposed animals had the highest levels. Protein levels in BAL fluid were more than five times higher in Cu-exposed animals compared to other metal treatments at 16 and 48 h. At the 0.1 micromol/kg dose, only Cu induced significant neutrophilia at 16 and 48 h. For the 1.0 micromol/kg dose, all metals tested induced significant neutrophilia, with mean neutrophil numbers for Cu and Mn significantly higher compared to the other metals. At 48 h, neutrophil numbers were still elevated in all metal exposures. Only Mn caused substantial eosinophilia. At the 1.0 micromol/kg dose, only Cu induced macrophage inflammatory protein-2 (MIP-2) mRNA at 4 h. By 48 h, induction of MIP-2 mRNA was observed for all metal exposures except Cu, which subsequently returned to baseline levels. On an equimolar basis, Cu was the most proinflammatory metal, followed by Mn and Ni, while V, Fe(II), and Zn induced similar levels of inflammation. Overall, there were many similarities in the pulmonary responses of the metals we tested. However, we also observed divergent, metal-specific responses. These differential responses suggest that metals induce pulmonary inflammation by differing pathways or combinations of signals.
Copyright 2001 Academic Press.