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. 2010 Feb;22(2):169-78.
doi: 10.3109/08958370903161232.

Effects of Metal Compounds With Distinct Physicochemical Properties on Iron Homeostasis and Antibacterial Activity in the Lungs: Chromium and Vanadium

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Effects of Metal Compounds With Distinct Physicochemical Properties on Iron Homeostasis and Antibacterial Activity in the Lungs: Chromium and Vanadium

Mitchell D Cohen et al. Inhal Toxicol. .
Free PMC article

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 (VV; 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 microg metal/m3. Differences in effects on local bacterial resistance between the two VV, and between each CrVI, 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.

Figures

Figure 1
Figure 1
Lung V and Cr burdens at Day 0 (i.e., pre-infection) and Day 3 of infection with Listeria. Each bar represents the average burden (ng V or ng Cr; ± SE) in the lungs of n = 5 (Day 0; solid bar) or n = 8–10 (Day 3; hatched bar) rats/exposure (5 hr/d, for 5 consecutive days) to insoluble V2O5, soluble NaVO3, insoluble CaCrO4, or soluble Na2CrO4. *Value significantly (p < 0.05) different from that in rats analyzed on Day 0.
Figure 2
Figure 2
Pre-infection levels of lavagable Fe in lungs of rats that had been exposed for 5 hr/d for 5 days to soluble or insoluble forms of V or Cr. Each value reported is the mean (± SE) obtained from 5–10 rats/subset. *Level significantly differs from air control value (p-value indicated above each bar); level significantly differs from solubility-matched Cr counterpart at p < 0.05.
Figure 3
Figure 3
Pre-infection levels of lavagable transferrin (solid bar/specific agent set) and ferritin (hatched bar/specific agent set) in lungs of rats that had been exposed for 5 hr/d for 5 days to soluble or insoluble forms of V or Cr. Each value reported is the mean (± SE) obtained from 5–10 rats/subset. At p < 0.05, *level significantly differs from air control value; level significantly differs from solubility-matched Cr counterpart; #level significantly differs from soluble counterpart.
Figure 4
Figure 4
Pre-infection levels of MIP-2 (solid bar/specific agent set) and TNF-α (hatched bar/specific agent set) in lungs of rats that had been exposed for 5 hr/d for 5 days to soluble or insoluble forms of V or Cr. Each value reported is the mean (± SE) obtained from 5–10 rats/subset. At p < 0.05, *level significantly differs from air control levels; level significantly differs from soluble counterpart; #level significantly differs from solubility-matched Cr counterpart
Figure 5
Figure 5
Relative change (at 72 hr) from air control rat bacterial levels in lungs of rats that had been exposed 5 hr/d for 5 days to soluble or insoluble forms of V or Cr prior to infection. Each bar represents mean (± SE) of 10 rats/subset. At p < 0.05: *percent (%) change from air control levels was significant; % change significantly differs from opposing solubility counterpart (within metal set); #% change significantly differs from solubility-matched V counterpart.
Figure 6
Figure 6
Relative difference in Listeria burden in lungs of rats at Day 3 post-infection as a function of Day 0 lung metal burdens. Each bar represents mean (± SE) (from n = 10 Day 3 rats/agent) average percentage difference in Listeria levels compared to respective values in air controls, in the context of ng V (or Cr) in lungs at Day 0. Value significantly (p < 0.05) different from that in rats in V counterparts matched for relative solubilities; *value significantly different from that of opposing solubility counterpart (within metal set).

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