Inhalation of residual oil fly ash (ROFA) impairs lung defense in susceptible populations. Bioavailability of soluble transition metals appears to play a key role in compromised lung defense caused by ROFA exposure. We evaluated the effect of soluble metals on lung defense in animals pre-exposed to ROFA followed by pulmonary challenge with a bacterial pathogen. ROFA was collected from Boston Edison, Co., Everett, MA, suspended in saline, incubated for 24 hr at 37 degrees C, and separated into soluble (ROFA-Sol) and insoluble (ROFA-Insol) fractions. A portion of ROFA-Sol was treated with the metal-binding resin, Chelex, for 24 hr at 37 degrees C. Sprague-Dawley rats were intratracheally dosed at day 0 with 1.0 mg/100 g body wt of ROFA-Insol, ROFA-Sol, saline, saline + Chelex, or ROFA-Sol + Chelex. At day 3, 5x10 to the 5 power Listeria monocytogenes were intratracheally instilled into rats from each treatment group. At days 6, 8 and 10, left lungs were removed, homogenized, cultured, and colony forming units (CFUs) were counted to assess bacterial clearance. Treatment with ROFA-Sol before infection led to a marked increase in lung injury at all time points after inoculation, and a 50% increase in mortality in comparison to saline control rats. Treatment with ROFA-Insol, saline + Chelex, and ROFA-Sol + Chelex caused no significant increases in lung damage and mortality when compared to control. On day 6, a 34-fold increase in the number of bacterial CFUs was observed for the ROFA-Sol group when compared with saline control. By day 10, the ROFA-Sol group had 3693 times more lung CFUs than saline control, indicating its inability to effectively respond to the infection. None of the other groups had significant impairments in bacterial clearance. In summary, exposure to ROFA-Sol suppressed the lung response to infection. Upon removal of soluble metals from ROFA, there was no alteration in lung defense mechanisms. Soluble metals present in ROFA may play a key role in increased susceptibility to pulmonary infection in exposed populations.
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee