title: Disruption of iron homeostasis as a mechanism of biologic effect by ambient air pollution particles.
abstract: Several features of the clinical presentation and changes in physiology and pathology following exposure to many diverse ambient air pollution particles are comparable, suggesting a common mechanism for their biological effect. We propose that a mechanism of biological effect common to many ambient air pollution particles is a disruption of iron homeostasis in cells and tissues. Among traits shared by every particle-related lung injury is the introduction of a solid-liquid interface into the respiratory tract. All surfaces of particulate matter have some concentration of oxygen-containing functional groups. As a result of its electropositivity, Fe(3+) has a high affinity for oxygen-donor ligands and will react with these groups at the particle surface. Retained particles accumulate metal from available sources in a cell and tissue, and this complexed iron mediates oxidant generation. In addition to complexation onto the solid-liquid interface provided by the surface of particulate matter (PM), there are several alternative pathways by which metal homeostasis in the lower respiratory tract can be disrupted following exposure to ambient air pollution particles to affect an oxidative stress. Evidence suggests that disruption in iron homeostasis following exposures to ambient air pollution particles is an initial event in their biological effect. An association between metal equilibrium in the lower respiratory tract and biological effect in the lung could explain the observed differential toxicity of ultrafine, fine, and coarse particles and disparities in host susceptibility.
authors.affiliation: Clinical Research Branch, Human Studies Division, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27599, USA. ghio.andy@epa.gov
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Cohen
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000502:physiology*; D010316:Particle Size
chemical_list: D000393:Air Pollutants; D007501:Iron