Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity

The extent of adverse health effects, including induction/ exacerbation of infectious lung disease, arising from entrainment of equivalent amounts ( or exposure to a fixed increment) of fine particulate matter ( PM2.5) can vary from region to region or city to city in a region. To begin to explain how differing effects on host resistance might arise after exposure to PM2.5 from various sites, we hypothesized that select metals ( e. g., V, Al, and Mn) in each PM2.5 caused changes in alveolar macrophage ( AM) Fe status that, ultimately, would lead to altered antibacterial function. To test this, iron-response protein ( IRP) binding activity in a rat AM cell line was assessed after exposure to Fe alone and in conjunction with V, Mn, and/ or Al at ratios of V: Fe, Al: Fe, or Mn: Fe encountered in PM2.5 samples from New York City, Los Angeles, and Seattle. Results indicated that V and Al each significantly altered IRP activity, though effects were not consistently ratio- ( i. e., dose-) dependent; Mn had little impact on activity. We conclude that the reductions in Fe status detected here via the IRP assay arose, in part, from effects on transferrin- mediated Fe3+ delivery to the AM. Ongoing studies using this assay are allowing us to better determine: ( 1) whether mass ( and/ or molar) relationships between Fe and V, Al, and/ or Mn in any PM2.5 sample consistently govern the extent of change in AM Fe status; ( 2) how much any specified PM2.5 constituent ( metal or nonmetal) contributes to the overall disruption of Fe status found induced by an intact parent sample; and ( 3) whether induced changes in binding activity are relatable to other changes expected to occur in the AM, that is, in IRP- dependent mRNA/ levels of ferritin/ transferrin receptor and Fe- dependent functions. These studies demonstrate that pollutant- induced effects on lung cell Fe status can be assessed in a reproducible manner using an assay that can be readily performed by investigators who might otherwise have no access to other very costly analytical equipment, such as graphite atomic absorption or x- ray fluorescence spectro( photo) meters.