The role of iron in Libby amphibole-induced acute lung injury and inflammation

Shannahan, JH; Ghio, AJ; Schladweiler, MC; Mcgee, JK; Richards, JH; Gavett, SH; Kodavanti, UP

HERO ID

759001

Reference Type

Journal Article

Year

2011

Language

English

PMID

21605006

HERO ID 759001
In Press No
Year 2011
Title The role of iron in Libby amphibole-induced acute lung injury and inflammation
Authors Shannahan, JH; Ghio, AJ; Schladweiler, MC; Mcgee, JK; Richards, JH; Gavett, SH; Kodavanti, UP
Journal Inhalation Toxicology
Volume 23
Issue 6
Page Numbers 313-323
Abstract 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 4.99 µm ± 4.53 and width 0.28 µm ± 0.19) asbestos-induced inflammogenic effects in vitro and in vivo. LA contained acid-leachable Fe and silicon. In a cell-free media containing FeCl(3), LA bound #17 µg of Fe/mg of fiber and increased reactive oxygen species 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 increased IL-8 expression, which was 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 (300 µL), DEF (1 mg), FeCl(3) (21 µg), LA (0.5 mg), FeLA (0.5 mg), or LA + DEF (0.5 mg). LA caused BALF neutrophils to increase 24 h post-exposure. Loading of Fe on LA but not chelation slightly decreased neutrophilic influx (LA + DEF > LA > FeLA). At 4 h post-exposure, LA-induced lung expression of MIP-2 was 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 may be inhibited in the presence of surface-complexed or cellular bioavailable Fe. Cell and tissue Fe-overload conditions may influence the pulmonary injury and inflammation caused by fibers.
Doi 10.3109/08958378.2011.569587
Pmid 21605006
Wosid WOS:000290935500001
Url /www.informahealthcare.com
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword Libby amphibole; iron homeostasis; inflammation
Is Qa No