title: Wood Smoke Particle Sequesters Cell Iron to Impact a Biological Effect.
abstract: The biological effect of an inorganic particle (i.e., silica) can be associated with a disruption in cell iron homeostasis. Organic compounds included in particles originating from combustion processes can also complex sources of host cell iron to disrupt metal homeostasis. We tested the postulate that (1) wood smoke particle (WSP) sequesters host cell iron resulting in a disruption of metal homeostasis, (2) this loss of essential metal results in both an oxidative stress and biological effect in respiratory epithelial cells, and (3) humic-like substances (HULIS), a component of WSP, have a capacity to appropriate cell iron and initiate a biological effect. BEAS-2B cells exposed to WSP resulted in diminished concentrations of mitochondrial (57)Fe, whereas preincubation with ferric ammonium citrate (FAC) prevented significant mitochondrial iron loss after such exposure. Cellular oxidant generation was increased after WSP exposure, but this signal was diminished by coincubation with FAC. Similarly, exposure of BEAS-2B cells to 100 μg/mL WSP activated mitogen-activated protein (MAP) kinases, elevated NF-E2-related factor 2/antioxidant responsive element (Nrf2 ARE) expression, and provoked interleukin (IL)-6 and IL-8 release, but all these changes were diminished by coincubation with FAC. The biological response to WSP was reproduced by exposure to 100 μg/mL humic acid, a polyphenol comparable to HULIS included in the WSP that complexes iron. We conclude that (1) the biological response following exposure to WSP is associated with sequestration of cell iron by the particle, (2) increasing available iron in the cell diminished the biological effects after particle exposure, and (3) HULIS included in WSP can sequester the metal initiating the cell response.
authors.affiliation: US Environmental Protection Agency , Chapel Hill, North Carolina 27599, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.affiliation: US Environmental Protection Agency , Chapel Hill, North Carolina 27599, United States.
authors.forename: Joleen M
authors.initials: JM
authors.lastname: Soukup
authors.affiliation: US Environmental Protection Agency , Chapel Hill, North Carolina 27599, United States.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Dailey
authors.affiliation: US Environmental Protection Agency , Chapel Hill, North Carolina 27599, United States.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Tong
authors.affiliation: Physician Assistant Program, Methodist University , Fayetteville, North Carolina 28311, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kesic
authors.affiliation: The Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.
authors.forename: G R Scott
authors.initials: GR
authors.lastname: Budinger
authors.affiliation: Section of Pulmonary and Critical Care and Lung Injury Center , Department of Medicine, Chicago, Illinois 60637, United States.
authors.forename: Gökhan M
authors.initials: GM
authors.lastname: Mutlu
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D006812:Humic Substances; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014157:Transcription Factors / Q000235:genetics; D014934:Wood
chemical_list: C110547:DMRT1 protein; D006812:Humic Substances; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D012906:Smoke; D014157:Transcription Factors; D007501:Iron; D020928:Mitogen-Activated Protein Kinases