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

Abstract

In situ reactions of metal ions or their compounds are important mechanisms by which particles alter lung immune responses. We 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 penta-valent 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 (5 hr/d for 5 d) of each at 100 μg 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 there were significant increases in production of select cytokines/chemokines). 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.

Exposure to bis(maltolato)oxovanadium(IV) increases levels of hepcidin mRNA and impairs the homeostasis of iron but not that of manganese

“…Specifically, V V has a significant local effect, causing significant increases in cytokines, which may help explain the toxic effects of these metals when they are inhaled (Ghio and Cohen, 2005;Prophete et al, 2006;Cohen et al, 2010). It has been reported that the exposure of human bronchial epithelial cells to residual oil fly ash containing V, Ni and Fe produces significant increases in IL-8, IL-6 and TNF-a (Carter et al, 1997) and that the phosphorylation of MAPK proteins may mediate the metal-induced expression of inflammatory proteins in these cells .…”

“…The appearance of oxidative stress is associated with an inflammatory response. Vanadium exposure has been related with cytokine production (Dye et al, 1999), inflammatory changes in the upper and lower respiratory tracts (Pierce et al, 1996;Cohen et al, 2010) and lung tumours (Assem and Levy, 2012). However, other authors have suggested that V may mediate the inhibition of different forms of cancer (Das et al, 2012).…”

Vanadium pentoxide increased PTEN and decreased SHP1 expression in NK-92MI cells, affecting PI3K-AKT-mTOR and Ras-MAPK pathways

“…Water-insoluble particles like V 2 O 5 are ingested by resident alveolar macrophages. Once in a macrophage phagosome, the particles undergo slow dissolution which generate free ions that can potentially exit the cells, then enter/cross through epithelial cells and ultimately into erythrocytes, and so become a part of the generic circulation (Cohen et al 2010). It is these latter now-solubilized forms of vanadium to which NK cells are most likely exposed in situ (Roberts et al 2004).…”

Immunotoxicology of arc welding fume: Worker and experimental animal studies

“…Moreover, Ghio and Cohen (2005) have theorized that the immunomodulatory effect of particulate matter, such as welding fume, may involve a disruption of Fe homeostasis in cells and tissues. It is possible that other metals may compete with Fe so that lung phagocytes become Fe-insufficient and unable to function properly, while simultaneously allowing for greater free Fe to remain available for pathogens (Cohen et al, 2010). A subsequent study by Palmer et al (2006) revealed that, surprisingly, despite high Fe loads and a low unsaturated Fe-binding capacity in sputum, no overt inflammatory response was found in blood or sputum of welders with a median employment of 10 years.…”