Enhanced allergic sensitization by residual oil fly ash particles is mediated by soluble metal constituents

Epidemiological studies have demonstrated an association between elevated l evels of particulate matter (PM) air pollutants and exacerbation of asthma symptoms. We have shown in a Brown Norway (BN) rat model of house dust mite (HDM) allergy that preexposure to residual oil By ash (ROFA) particles enh anced the sensitization phase such that the secondary immune response and a ssociated lung injury were increased after allergen challenge. To determine whether the metals present in ROFA mediated this effect, BN rats were intr atracheally instilled with either ROFA (1000 mu g) or acidified saline + Ni SO4 (105.12 mu g), VSO4 (98.2 mu g), FeSO4 (58.49 mu g), or a mixture (Mix) of each metal. HDM-specific IgE was higher in the serum of the ROFA, Ni, V , and Mix groups than in the HDM group after challenge, and antigen-induced bronchoconstriction responses were increased in the Ni group. Lymphocyte p roliferation to antigen was increased in the ROFA, Ni, and V groups compare d to controls. Total protein and eosinophil peroxidase levels were elevated in the Fe group, and eosinophil numbers in the bronchoalveolar lavage flui d (BALF) were increased in the ROFA and Fe groups compared to HDM control. IL-5 and IL-13 mRNA expression was also increased in the lung tissue of all metal and ROFA-treated groups, while BALF IL-10 was elevated in the Fe and Mix groups, and IL-6 and TNF-alpha were elevated in the metal and ROFA-tre ated groups compared to controls. These results suggest that ROFA's metalli c constituents mediate enhancement of sensitization to HDM and that pulmona ry inflammation may play a role in this adjuvant effect. (C) 2000 Academic Press.