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OXIDANT GENERATION PROMOTES IRON SEQUESTRATION IN BEAS-2B CELLS EXPOSED TO ASBESTOS
Citation:
WANG, Z., Y. WU, J. STONEHUERNER, L. A. DAILEY, J. E. RICHARDS, I. JASPERS, C. A. PIANTADOSI, AND A. J. GHIO. OXIDANT GENERATION PROMOTES IRON SEQUESTRATION IN BEAS-2B CELLS EXPOSED TO ASBESTOS. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. American Thoracic Society, New York, NY, 34(3):286-292, (2006).
Impact/Purpose:
We tested the hypothesis that the cellular response to asbestos includes the transport and sequestration of iron
Description:
Lung injury following 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) upregulation 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 (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 superoxide 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 IL-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.