A role for associated transition metals in the immunotoxicity of inhaled ambient particulate matter

Epidemiologic studies demonstrate that infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals following exposure to ambient particulate matter (PM). This laboratory has previously demonstrated that a single inhalation exposure of Streptococcus pneumoniae-infected rats to concentrated ambient PM2.5 (particulate matter with aerodynamic diameter less than or equal to 2.5 mum) from New York City (NYC) air exacerbates the infection process and alters pulmonary and systemic immunity. Although these results provide some basis for explaining the epidemiologic findings, the identity of specific PM constituents that might have been responsible for the worsening pneumonia in exposed hosts remains unclear. Thus, studies were performed to correlate the physicochemical attributes of ambient PM2.5 with its in vivo immunotoxicity to identify and characterize the role of constitutive transition metals in exacerbating an ongoing streptococcal infection. Uninfected or previously infected rats were exposed in the laboratory to soluble divalent Fe, Mn, or Ni chloride salts. After exposure, uninfected rats were sacrificed and their lungs were lavaged. Lungs from infected hosts were used to evaluate changes in bacterial clearance and effects of exposure on the extent/severity of infection. Results demonstrated that inhalation of Fe altered innate and adaptive immunity in uninfected hosts, and both Fe and Ni reduced pulmonary bacterial clearance in previously infected rats. The effects on clearance produced in infected Fe-exposed rats were similar to those seen in infected rats exposed to ambient NYC PM. Taken together, these studies demonstrate that inhaled ambient PM can worsen the outcome of an ongoing pulmonary infection and that associated Fe may play some role in the immunotoxicity.