title: Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity.
abstract: 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.
authors.affiliation: NYU-EPA Particulate Matter Health Research Center, Nelson Institute, New York University School of Medicine Tuxedo, New York 10987, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Doherty
authors.forename: C
authors.initials: C
authors.lastname: Prophete
authors.forename: P
authors.initials: P
authors.lastname: Maciejczyk
authors.forename: K
authors.initials: K
authors.lastname: Salnikow
authors.forename: T
authors.initials: T
authors.lastname: Gould
authors.forename: T
authors.initials: T
authors.lastname: Larson
authors.forename: J
authors.initials: J
authors.lastname: Koenig
authors.forename: P
authors.initials: P
authors.lastname: Jaques
authors.forename: C
authors.initials: C
authors.lastname: Sioutas
authors.forename: J T
authors.initials: JT
authors.lastname: Zelikoff
authors.forename: M
authors.initials: M
authors.lastname: Lippmann
authors.forename: M D
authors.initials: MD
authors.lastname: Cohen
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D035925:Iron-Regulatory Proteins / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D052638:Particulate Matter / Q000032:analysis / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats
chemical_list: D000393:Air Pollutants; D035925:Iron-Regulatory Proteins; D052638:Particulate Matter; D007501:Iron