Oxidant generation promotes iron sequestration in BEAS-2B cells exposed to asbestos.

Published

Journal Article

Lung injury after asbestos exposure is associated with an oxidative stress that is catalyzed by iron in the fiber matrix, complexed to the surface, or both. We tested the hypothesis that the cellular response to asbestos includes the transport and sequestration of this iron through (1) generation of superoxide for ferrireduction, (2) up-regulation of divalent metal transporter-1 (DMT1) for intracellular transport of Fe2+, and (3) increased production of cellular ferritin where the metal is stored in a catalytically less reactive state. BEAS-2B cells with normal and elevated Cu,Zn superoxide dismutase (SOD) expression were employed for in vitro investigations. After exposure of these cells to asbestos, we demonstrated by fluorescence methodology a significantly increased generation of SOD with ferrireductive capacity. Fiber exposure also increased DMT1 protein and mRNA expression in the BEAS-2B cells. Incubation with asbestos elevated cellular iron and ferritin concentrations, and these responses were diminished in cells with an enhanced expression of SOD. Finally, fiber exposure increased supernatant concentrations of interleukin 8, but this inflammatory mediator was actually increased in cells with elevated SOD expression. We conclude that the response of respiratory epithelial cells to asbestos includes oxidant-mediated mechanisms to sequester catalytically active iron associated with the fiber.

Full Text

Duke Authors

Cited Authors

  • Wang, X; Wu, Y; Stonehuerner, JG; Dailey, LA; Richards, JD; Jaspers, I; Piantadosi, CA; Ghio, AJ

Published Date

  • March 2006

Published In

Volume / Issue

  • 34 / 3

Start / End Page

  • 286 - 292

PubMed ID

  • 16272461

Pubmed Central ID

  • 16272461

Electronic International Standard Serial Number (EISSN)

  • 1535-4989

International Standard Serial Number (ISSN)

  • 1044-1549

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2004-0275oc

Language

  • eng