Thebiological effect of an inorganic particle (i.e., silica) canbe associated with a disruption in cell iron homeostasis. Organiccompounds included in particles originating from combustion processescan also complex sources of host cell iron to disrupt metal homeostasis.We tested the postulate that (1) wood smoke particle (WSP) sequestershost cell iron resulting in a disruption of metal homeostasis, (2)this loss of essential metal results in both an oxidative stress andbiological effect in respiratory epithelial cells, and (3) humic-likesubstances (HULIS), a component of WSP, have a capacity to appropriatecell iron and initiate a biological effect. BEAS-2B cells exposedto WSP resulted in diminished concentrations of mitochondrial 57Fe, whereas preincubation with ferric ammonium citrate (FAC)prevented significant mitochondrial iron loss after such exposure.Cellular oxidant generation was increased after WSP exposure, butthis signal was diminished by coincubation with FAC. Similarly, exposureof BEAS-2B cells to 100 μg/mL WSP activated mitogen-activatedprotein (MAP) kinases, elevated NF-E2-related factor 2/antioxidantresponsive element (Nrf2 ARE) expression, and provoked interleukin(IL)-6 and IL-8 release, but all these changes were diminished bycoincubation with FAC. The biological response to WSP was reproducedby exposure to 100 μg/mL humic acid, a polyphenol comparableto HULIS included in the WSP that complexes iron. We conclude that(1) the biological response following exposure to WSP is associatedwith sequestration of cell iron by the particle, (2) increasing availableiron in the cell diminished the biological effects after particleexposure, and (3) HULIS included in WSP can sequester the metal initiatingthe cell response. [ABSTRACT FROM AUTHOR]