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

S. P. Doherty, Colette M. Prophete, P. Maciejczyk, K. Salnikow, T. Gould, T. Larson, J. Koenig, P. Jaques, C. Sioutas, J. T. Zelikoff, M. Lippmann, M. D. Cohen

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalInhalation Toxicology
Volume19
Issue number6-7
DOIs
StatePublished - Apr 2007
Externally publishedYes

Fingerprint

Iron-Regulatory Proteins
Alveolar Macrophages
Protein Binding
Iron
Assays
Metals
Nonmetals
Alveolar Epithelial Cells
Pulmonary diseases
Transferrin Receptors
Particulate Matter
Graphite
Los Angeles
Transferrin
Ferritins
Lung Diseases
Communicable Diseases
Rats
Fluorescence
Cells

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity. / Doherty, S. P.; Prophete, Colette M.; Maciejczyk, P.; Salnikow, K.; Gould, T.; Larson, T.; Koenig, J.; Jaques, P.; Sioutas, C.; Zelikoff, J. T.; Lippmann, M.; Cohen, M. D.

In: Inhalation Toxicology, Vol. 19, No. 6-7, 04.2007, p. 553-562.

Research output: Contribution to journalArticle

Doherty, SP, Prophete, CM, Maciejczyk, P, Salnikow, K, Gould, T, Larson, T, Koenig, J, Jaques, P, Sioutas, C, Zelikoff, JT, Lippmann, M & Cohen, MD 2007, 'Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity', Inhalation Toxicology, vol. 19, no. 6-7, pp. 553-562. https://doi.org/10.1080/08958370701280481
Doherty, S. P. ; Prophete, Colette M. ; Maciejczyk, P. ; Salnikow, K. ; Gould, T. ; Larson, T. ; Koenig, J. ; Jaques, P. ; Sioutas, C. ; Zelikoff, J. T. ; Lippmann, M. ; Cohen, M. D. / Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity. In: Inhalation Toxicology. 2007 ; Vol. 19, No. 6-7. pp. 553-562.
@article{65fe25ffc2cb49848c3524565049eb36,
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.",
author = "Doherty, {S. P.} and Prophete, {Colette M.} and P. Maciejczyk and K. Salnikow and T. Gould and T. Larson and J. Koenig and P. Jaques and C. Sioutas and Zelikoff, {J. T.} and M. Lippmann and Cohen, {M. D.}",
year = "2007",
month = "4",
doi = "10.1080/08958370701280481",
language = "English (US)",
volume = "19",
pages = "553--562",
journal = "Inhalation Toxicology",
issn = "0895-8378",
publisher = "Informa Healthcare",
number = "6-7",

}

TY - JOUR

T1 - Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity

AU - Doherty, S. P.

AU - Prophete, Colette M.

AU - Maciejczyk, P.

AU - Salnikow, K.

AU - Gould, T.

AU - Larson, T.

AU - Koenig, J.

AU - Jaques, P.

AU - Sioutas, C.

AU - Zelikoff, J. T.

AU - Lippmann, M.

AU - Cohen, M. D.

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34248574733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248574733&partnerID=8YFLogxK

U2 - 10.1080/08958370701280481

DO - 10.1080/08958370701280481

M3 - Article

C2 - 17497533

AN - SCOPUS:34248574733

VL - 19

SP - 553

EP - 562

JO - Inhalation Toxicology

JF - Inhalation Toxicology

SN - 0895-8378

IS - 6-7

ER -