Accumulation of iron in the rat lung after tracheal instillation of dieselparticles

Oxidant generation catalyzed by metals has been postulated to account for a lung injury following exposure to air pollution particles. In particles th at are predominantly carbonaceous, it is difficult to implicate such an oxi dative stress as the responsible mechanism, since concentrations of metals can be extremely low. Comparable to these air pollution particles, mineral oxide particles can include only minute amounts of metal, but lung injury f ollowing their exposure can be associated with an accumulation of endogenou s iron from the host and an oxidative stress. We tested the hypothesis that diesel exhaust particulate (DEP) effects an accumulation of biologically a ctive iron in the rat lung, with both oxidative stress and a lung injury re sulting. Characterization of the DEP confirmed a high concentration of carb on, whereas metals were low in quantity. The concentration of total lavage iron in animals instilled with saline was low, but this concentration incre ased with exposure to DEP. Non-heme iron in lung tissue was similarly eleva ted after instillation of the diesel product. Particle instillation was ass ociated with a decrease in lavage ascorbate concentration supporting an oxi dative stress. Relative to saline exposure, DEP resulted in elevated lavage concentrations of the inflammatory mediators macrophage inflammatory prote in-2 and tumor necrosis factor. Finally, an injury after particle instillat ion was evident with increased neutrophils and an elevation of lavage prote in and lactic dehydrogenase. We conclude that DEP exposure effected an accu mulation of iron in the rat lung. This accrual of iron was associated with an oxidative stress, release of oxidant-sensitive mediators, and a neutroph ilic lung injury.