Effects of metal compounds with distinct physicochemical properties on iron homeostasis and antibacterial activity in the lungs

Chromium and vanadium

Mitchell D. Cohen, Maureen Sisco, Colette M. Prophete, Kotaro Yoshida, Lung Chi Chen, Judith T. Zelikoff, Jason Smee, Alvin A. Holder, Jacqueline Stonehuerner, Debbie C. Crans, Andrew J. Ghio

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In situ reactions of metal ions or their compounds are important mechanisms by which particles alter lung immune responses. The authors hypothesized that major determinants of the immunomodulatory effect of any metal include its redox behavior/properties, oxidation state, and/or solubility, and that the toxicities arising from differences in physicochemical parameters are manifest, in part, via differential shifts in lung iron (Fe) homeostasis. To test the hypotheses, immunomodulatory potentials for both pentavalent vanadium (V V; as soluble metavanadate or insoluble vanadium pentoxide) and hexavalent chromium (CrVI; as soluble sodium chromate or insoluble calcium chromate) were quantified in rats after inhalation (5h/day for 5 days) of each at 100 μg metal/m3. Differences in effects on local bacterial resistance between the two VV, and between each Cr VI, agents suggested that solubility might be a determinant of in situ immunotoxicity. For the soluble forms, VV had a greater impact on resistance than CrVI, indicating that redox behavior/properties was likely also a determinant. The soluble VV agent was the strongest immunomodulant. Regarding Fe homeostasis, both VV agents had dramatic effects on airway Fe levels. Both also impacted local immune/airway epithelial cell Fe levels in that there were significant increases in production of select cytokines/chemokines whose genes are subject to regulation by HIF-1 (whose intracellular longevity is related to cell Fe status). Our findings contribute to a better understanding of the role that metal compound properties play in respiratory disease pathogenesis and provide a rationale for differing pulmonary immunotoxicities of commonly encountered ambient metal pollutants.

Original languageEnglish (US)
Pages (from-to)169-178
Number of pages10
JournalInhalation Toxicology
Volume22
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

Fingerprint

Vanadium
Chromium
Homeostasis
Iron
Metals
Lung
Solubility
Oxidation-Reduction
Pulmonary diseases
Vanadates
Chemokines
Metal ions
Toxicity
Rats
Genes
Inhalation
Cytokines
Oxidation
Epithelial Cells
Ions

Keywords

  • Chromium
  • Ferritin
  • Immunomodulation
  • Iron
  • Listeria
  • Pulmonary
  • Transferrin
  • Vanadium

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Effects of metal compounds with distinct physicochemical properties on iron homeostasis and antibacterial activity in the lungs : Chromium and vanadium. / Cohen, Mitchell D.; Sisco, Maureen; Prophete, Colette M.; Yoshida, Kotaro; Chen, Lung Chi; Zelikoff, Judith T.; Smee, Jason; Holder, Alvin A.; Stonehuerner, Jacqueline; Crans, Debbie C.; Ghio, Andrew J.

In: Inhalation Toxicology, Vol. 22, No. 2, 02.2010, p. 169-178.

Research output: Contribution to journalArticle

Cohen, MD, Sisco, M, Prophete, CM, Yoshida, K, Chen, LC, Zelikoff, JT, Smee, J, Holder, AA, Stonehuerner, J, Crans, DC & Ghio, AJ 2010, 'Effects of metal compounds with distinct physicochemical properties on iron homeostasis and antibacterial activity in the lungs: Chromium and vanadium', Inhalation Toxicology, vol. 22, no. 2, pp. 169-178. https://doi.org/10.3109/08958370903161232
Cohen, Mitchell D. ; Sisco, Maureen ; Prophete, Colette M. ; Yoshida, Kotaro ; Chen, Lung Chi ; Zelikoff, Judith T. ; Smee, Jason ; Holder, Alvin A. ; Stonehuerner, Jacqueline ; Crans, Debbie C. ; Ghio, Andrew J. / Effects of metal compounds with distinct physicochemical properties on iron homeostasis and antibacterial activity in the lungs : Chromium and vanadium. In: Inhalation Toxicology. 2010 ; Vol. 22, No. 2. pp. 169-178.
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