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Libby Amphibole-Induced Inflammation is Modulated by Iron In Vitro and In Vivo
Citation:
Shannahan, J., M. SCHLADWEILER, J. K. MCGEE, J. E. RICHARDS, A. J. GHIO, S. H. GAVETT, AND U. P. KODAVANTI. Libby Amphibole-Induced Inflammation is Modulated by Iron In Vitro and In Vivo. Presented at Society of Toxicology (SOT) Annual meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
This abstract examined the role of iron in Libby amphibole asbestos induced pulmonary injury in vitro and vivo. It provides insights into how iron can modulate pulmonary inflammation in cells and in the lung.
Description:
Complexation of host iron (Fe) to asbestos after exposure has been postulated as a mechanism of oxidative stress possibly contributing to in vivo pulmonary injury and variations in disease susceptibility. In a series of experiments, we examined the role of Fe in Libby amphibole (LA) induced toxicity in vitro and in vivo. In a cell free media, LA bound ≈16ug of Fe/mg of fiber and increased reactive oxygen species (ROS) generation, ≈3 fold; which was reduced by deferoxamine (DEF) treatment. To determine the role of Fe in LA-induced ROS generation and inflammation, BEAS2B cells were exposed to LA (50ug), Fe-loaded LA, or LA with DEF. No conditions altered HO-1 or ferritin mRNA expression. LA markedly increased IL-8 expression, which was significantly reduced by Fe loading but increased by DEF. To determine the role of Fe in LA-induced lung injury in vivo, spontaneously hypertensive rats were exposed intratracheally to either saline (300ul), DEF (lmg), FeC13 (21ug), LA (0.5mg), Fe-loaded LA (0.5mg), and LA+DEF (0.5mg). Neither FeC13 nor DEF increased bronchoalveolar lavage fluid (BALF) neutrophils compared to saline at 24h. LA caused BALF neutrophils to increase dramatically. Loading of Fe on LA but not chelation slightly decreased inflammation (LA+DEF>LA> Fe-loaded LA). At 4h post-exposure LA-induced lung mRNA expression of MIP-2 was significantly reduced in rats exposed to Fe-loaded LA but increased by DEF (LA+DEF > LA> Fe-loaded LA). Ferritin mRNA expression was elevated in rats exposed to Fe-loaded LA compared to LA control. HO-1 expression was unchanged due to LA exposure. In conclusion, the acute inflammatory response to LA exposure might be modified by the fiber's ability to complex Fe rather than redox cycling of fiber associated Fe and thus, Fe overload conditions may influence susceptibility to LA-induced pulmonary disease (This abstract does not represent US EPA policy).