title: Chronic exposure to perfluorinated compounds: Impact on airway hyperresponsiveness and inflammation.
abstract: Emerging epidemiological evidence reveals a link between lung disease and exposure to indoor pollutants such as perfluorinated compounds (PFCs). PFC exposure during critical developmental stages may increase asthma susceptibility. Thus, in a murine model, we tested the hypothesis that early life and continued exposure to two ubiquitous household PFCs, perfluorooctanoic acid (PFOA) and perflurooctanesulfonic acid (PFOS), can induce lung dysfunction that exacerbates allergen-induced airway hyperresponsiveness (AHR) and inflammation. Balb/c mice were exposed to PFOA or PFOS (4 mg/kg chow) from gestation day 2 to 12 wk of age by feeding pregnant and nursing dams, and weaned pups. Some pups were also sensitized and challenged with ovalbumin (OVA). We assessed lung function and inflammatory cell and cytokine expression in the lung and examined bronchial goblet cell number. PFOA, but not PFOS, without the OVA sensitization/challenge induced AHR concomitant with a 25-fold increase of lung macrophages. PFOA exposure did not affect OVA-induced lung inflammatory cell number. In contrast, PFOS exposure inhibited OVA-induced lung inflammation, decreasing total cell number in lung lavage by 68.7%. Interferon-γ mRNA in the lung was elevated in all PFC-exposed groups. Despite these effects, neither PFOA nor PFOS affected OVA-induced AHR. Our data do not reveal PFOA or PFOS exposure as a risk factor for more severe allergic asthma-like symptoms, but PFOA alone can induce airway inflammation and alter airway function.
authors.affiliation: Department of Physiology and Pathophysiology, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Min H
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Physiology and Pathophysiology, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Aruni
authors.initials: A
authors.lastname: Jha
authors.affiliation: Department of Physiology and Pathophysiology, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Oluwaseun O
authors.initials: OO
authors.lastname: Ojo
authors.affiliation: Department of Physiology and Pathophysiology, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mahood
authors.affiliation: Department of Physiology and Pathophysiology, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Sujata
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Physiology and Pathophysiology, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Karen A
authors.initials: KA
authors.lastname: Detillieux
authors.affiliation: Department of Chemistry, The University of Manitoba, Winnipeg, Canada; Department of Environmental Studies and Sciences, The University of Winnipeg, Richardson College for the Environment, Winnipeg, Canada; and Department of Chemistry, The University of Winnipeg, Richardson College for the Environment, Winnipeg, Canada.
authors.forename: Neda
authors.initials: N
authors.lastname: Nikoobakht
authors.affiliation: Department of Chemistry, The University of Manitoba, Winnipeg, Canada; Department of Environmental Studies and Sciences, The University of Winnipeg, Richardson College for the Environment, Winnipeg, Canada; and Department of Chemistry, The University of Winnipeg, Richardson College for the Environment, Winnipeg, Canada.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Wong
authors.affiliation: Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Mark
authors.initials: M
authors.lastname: Loewen
authors.affiliation: Department of Pediatrics and Child Health, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada;
authors.forename: Allan B
authors.initials: AB
authors.lastname: Becker
authors.affiliation: Department of Physiology and Pathophysiology, The University of Manitoba, Winnipeg, Canada; Department of Internal Medicine, The University of Manitoba, Winnipeg, Canada; Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Canada; andrew.halayko@med.umanitoba.ca.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D002210:Caprylates / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D020397:Goblet Cells / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy
chemical_list: D000393:Air Pollutants; D017738:Alkanesulfonic Acids; D002210:Caprylates; D005466:Fluorocarbons; D007371:Interferon-gamma; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid
keywords: asthma; environmental pollutant; interferon-γ; perfluorooctanoic acid; perflurooctanesulfonic acid