Functional groups on the surface of fibrous
silicates can complex
iron. We tested the postulate that (1)
asbestos complexes and sequesters host cell
iron resulting in a disruption of
metal homeostasis and (2) this loss of essential
metal results in an oxidative stress and
biological effect in respiratory epithelial cells. Exposure of BEAS-2B cells to 50 μg/mL
chrysotile resulted in diminished concentrations of mitochondrial
iron. Preincubation of these cells with 200 μM
ferric ammonium citrate (FAC) prevented significant mitochondrial
iron loss following the same exposure. The host response to
chrysotile included increased expression of the importer
divalent metal transporter-1 (DMT1) supporting a functional
iron deficiency. Incubation of BEAS-2B cells with both 200 μM FAC and 50 μg/mL
chrysotile was associated with a greater cell accumulation of
iron relative to either
iron or
chrysotile alone reflecting increased import to correct
metal deficiency immediately following fiber exposure. Cellular
oxidant generation was elevated after
chrysotile exposure and this signal was diminished by co-incubation with 200 μM FAC. Similarly, exposure of BEAS-2B cells to 50 μg/mL
chrysotile was associated with release of the proinflammatory mediators
interleukin (IL)-6 and
IL-8, and these changes were diminished by co-incubation with 200 μM FAC. We conclude that (1) the
biological response following exposure to
chrysotile is associated with complexation and sequestration of cell
iron and (2) increasing available
iron in the cell diminished the effects of
asbestos exposure.