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The Role of Iron in Libby Amphibole-Induced Lung Injury and Inflammation
Citation:
Shannahan, J., A. J. GHIO, M. SCHLADWEILER, J. K. MCGEE, J. E. RICHARDS, S. H. GAVETT, AND U. P. KODAVANTI. The Role of Iron in Libby Amphibole-Induced Lung Injury and Inflammation. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 23(6):313-323, (2011).
Impact/Purpose:
This study is a part of Libby Toxicology project at NHEERL (ORD's Libby Action-plan) to examine the mechanisms by which Libby amphibole asbestos induces lung injury and how that might be related to disease development.
Description:
Complexation of host iron (Fe) on the surface of inhaled asbestos fibers has been postulated to cause oxidative stress contributing to in vivo pulmonary injury and inflammation. We examined the role of Fe in Libby amphibole (LA; mean length 4.99um ± 4.53 and width 0.28um ± 0.19) asbestos-induced inflammogenic effects in vitro and in vivo. LA contained acid-leachable Fe and silicon. In a cell-free media containing FeCI3), LA bound ≈17ug of Fe/mg of fiber and increased reactive oxygen species (ROS) generation ≈3.5 fold; which was reduced by deferoxamine (DEF) treatment. In BEAS-2B cells exposure to LA, LA loaded with Fe (FeLA), or LA with DEF did not increase 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), FeCI3) (21ug), LA (0.5mg), FeLA (0.5mg), or LA+DEF (0.5mg). LA caused BALF neutrophils to increase dramatically at 24hr after exposure. Loading of Fe on LA but not chelation slightly decreased neutrophilic influx (LA+DEF>LA> FeLA). At 4hr post-exposure, LA-induced lung expression of MIP-2 was significantly reduced in rats exposed to FeLA but increased by LA+DEF (LA+DEF > LA > FeLA). Ferritin mRNA was elevated in rats exposed to FeLA compared to LA. In conclusion, the acute inflammatory response to respirable fibers and particles might be inhibited in the presence of surface-complexed or cellular bioavailable Fe. Thus, the cell and tissue Fe-overload conditions may influence -the pulmonary injury and inflammation caused by fibers.
