Differential ability of transition metals to induce pulmonary inflammation

Transition metals are components of airborne particles and have been implic ated in adverse health effects. The relative inflammatory potential of thes e metals is usually inferred from separate studies that focus on only one o r a few individual metals. Comparisons of relative potency among several me tals from these separate studies can be difficult. In one comprehensive stu dy, we measured the pulmonary effects of equimolar doses of six metals in s oluble form. Our purpose was to compare inflammatory potential and pulmonar y toxicity among individual transition metals. Rats received saline, 0.1 or 1.0 mu mol/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 dehydrog enase activity in BAL fluid; Cu- and Ni-exposed animals had the highest lev els. Protein levels in BAL fluid were more than five times higher in Cu-exp osed animals compared to other metal treatments at 16 and 48 h. At the 0.1 mu mol/kg dose, only Cu induced significant neutrophilia at 16 and 48 h. Fo r the 1.0 mu mol/kg dose, all metals tested induced significant neutrophili a, with mean neutrophil numbers for Cu and Mn significantly higher compared to the other metals. At 48 h, neutrophil numbers were still elevated in al l metal exposures. Only Mn caused substantial eosinophilia. At the 1.0 mu m ol/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 exposur es except Cu, which subsequently returned to baseline levels. On an equimol ar basis, Cu was the most proinflammatory metal, followed by Mn and Ni, whi le 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 diffe rential responses suggest that metals induce pulmonary inflammation by diff ering pathways or combinations of signals. (C) 2001 Academic Press.