| Ambient particulate matter (PM) causes increased cardiopulmonary morbidity and mortality, but the physicochemical determinants responsible for its biological effects are not understood. Iron is the predominant transition metal found in PM and may play a key role in the formation of extremely reactive oxygen species (ROS) resulting in adverse health effects. It is commonly recognized that soot is the essential component of PM which can serve as the carrier for co-pollutants such as gases and transition metals. This study was aimed to: (1) determine the pulmonary response to inhaled iron particles alone, (2) identify the interaction between iron and soot particles, and (3) examine respiratory responses in neonatal rats to better understand health effects of PM in susceptible subpopulations. A well-controlled and reproducible flame system was used to simulate a typical combustion process and to generate ultrafine iron, soot and the mixture of iron and soot particles. Sprague Dawley rats were exposed by inhalation to iron alone, soot alone, a combination of iron and soot particles, or filtered air 6 hr/day for 3 days. Measurements of intracellular iron bioavailability, oxidative stress, cytotoxicity, inflammatory response, NF-kappaB activation and histological features were performed to define mechanisms and consequences of acute respiratory toxicity following exposure to particles. Results from the present study led to the conclusion that inhalation of iron particles alone caused mild respiratory responses including ferritin induction, oxidative stress and inflammatory response in a dose-dependent manner. No detectable alterations were observed following exposure to soot particles alone. However, exposure to a combination of iron and soot particles resulted in a synergistic interaction demonstrated as significant increases in ferritin expression, oxidative stress, proinflammatory responses, CYP450s induction, and NF-kappaB activation. Furthermore, remarkable oxidative injury was observed in the lungs of neonatal rats following exposure to iron and soot particles. |
