title: Tissue Phthalate Levels Correlate With Changes in Immune Gene Expression in a Population of Juvenile Wild Salmon.
abstract: Phthalates have detrimental effects on health and have been shown to dysregulate the immune system of mammals, birds, and fish. We recently reported that di(2-ethylhexyl) phthalate exposure reduces the abundance and inhibits the proliferation of rainbow trout (Oncorhynchus mykiss) IgM(+) B lymphocytes and expression of secreted immunoglobulin heavy-chain mu transcripts in an in vitro culture system. We proposed that phthalates act as immunomodulators by modifying the normal B cell-activation pathways by accelerating B cell differentiation while suppressing plasmablast expansion, thus resulting in fewer IgM-secreting plasma cells. This hypothesis was tested here in an in vivo field study of juvenile Dolly Varden (Salvelinus malma) from a plastic-polluted lake in the Gulf of Alaska. Fish tissues were analyzed for both phthalate levels using liquid chromatography-coupled tandem mass spectrometry and for changes in immune gene expression using reverse transcriptase-real time polymerase chain reaction. Results showed that fish with higher tissue levels of di(2-ethylhexyl) phthalate, di(n-butyl) phthalate, and/or dimethyl phthalate expressed significantly fewer secreted and membrane-bound immunoglobulin heavy-chain mu and Blimp1 transcripts in their hematopoietic tissue. This suggests that in vivo uptake of phthalates in fish changes the expression of B cell-specific genes. Chronic exposure to phthalates likely dysregulates normal B-lymphoid development and antibody responses in salmonids and may increase susceptibility to infection. Given the conserved nature of B-lineage cells in vertebrate animals, other marine species may be similarly affected by chronic phthalate exposure.
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA, 23185, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Martins
authors.affiliation: Environment and Natural Resources Institute, The University of Alaska Anchorage, Anchorage, AK, 99508, USA.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hagedorn
authors.affiliation: Department of Chemistry, The University of Alaska Anchorage, Anchorage, AK, 99508, USA.
authors.forename: Shareen
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department of Chemistry, The University of Alaska Anchorage, Anchorage, AK, 99508, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kennish
authors.affiliation: Environment and Natural Resources Institute, The University of Alaska Anchorage, Anchorage, AK, 99508, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Applegate
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA, 23185, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Leu
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA, 23185, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Epp
authors.affiliation: Gulf of Alaska Keeper, Anchorage, AK, 99516, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Pallister
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA, 23185, USA. pxzwol@wm.edu.
authors.forename: Patty
authors.initials: P
authors.lastname: Zwollo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D029941:Fish Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D010795:Phthalic Acids / Q000378:metabolism* / Q000633:toxicity; D012474:Salmon / Q000502:physiology*; D014874:Water Pollutants, Chemical / Q000378:metabolism* / Q000633:toxicity
chemical_list: D029941:Fish Proteins; D010795:Phthalic Acids; D014874:Water Pollutants, Chemical; C032279:phthalic acid