Soluble metals of residual oil fly ash (ROFA), an air pollutant from the combustion of fossil fuel, may be associated with lung infection and morbidity in susceptible populations. The present objective was to determine which soluble metal in ROFA was associated with decreased clearance of bacteria from the lungs of rats. At day 0, rats were intratracheally instilled (IT) with soluble NiCl2 (55.7ug), FeSO4 (37.2ug), AlSO4 (46.6ug), ZnCl2 (8.69ug), or a mixture of the metals in quantities present in a 2.0 mg dose of ROFA as determined by elemental analysis. On day 3, rats were infected with an IT dose of 5x10^4 Listeria monocytogenes and euthanized on days 6, 8 and 10. The left lungs were homogenized to assess bacterial load, and bronchoalveolar lavage (BAL) was performed on the right lungs to measure lung injury and inflammation. Cells from lymph nodes were analyzed to determine phenotype. On day 6, rats exposed to Ni or the metal mixture had an increased bacterial lung burden as compared to all groups, and rats exposed to Zn had a higher bacterial load when compared to rats exposed to Al, Fe, or saline control. Lactate dehydrogenase and albumin levels in BAL fluid were 3 times greater in the Ni and mixed metal groups on day 6 as compared to controls. Treatment with Ni and the metal mixture resulted in a 3 and 2 fold increase, respectively, in the number of cells in the BAL at all time points. The number of T cells in the BAL of the Ni and the mixed metal groups was decreased on day 6 and the number of natural killer cells was decreased in the Ni group at all time points as compared to controls. The ratio of CD4+ to CD8+ T cells in the BAL and in the lymph nodes was higher in the Ni and mixed metal groups on day 6. In summary, rats treated with soluble Ni, alone or in a mixture with soluble Fe, Zn, and Al, showed increased lung injury, decreased bacterial clearance, and altered lymphocyte profiles at early time points post-infection. Thus, soluble Ni may play an important role in the increase in susceptibility to infection after ROFA exposure.
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana