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Maternal Bisphenol A (BPA) Exposure Induces Allergic Sensitization In Animal Model
Abstracts S181
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
Allergic Asthma and the Developing Immune System: A Pilot Study C. M. Pucheu-Haston1, L. B. Copeland2, M. D. W. Ward2; 1Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC, 2 National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC. RATIONALE: The predisposition towards atopic disease begins early in life, and the risk of developing asthma is heightened following prenatal exposure to some compounds. Nonetheless, the effect of gestational aeroallergen exposure on the developing immune system is unclear. Project objectives are 1) to develop an animal model of gestational aeroallergen exposure, 2) to determine the response of gestationallyexposed offspring to subsequent allergen exposure and 3) to determine the effects of allergen exposure during pregnancy on the development of maternal sensitization. METHODS: Dams: BALB/c mice received Metarhizium anisopliae extract (MACA) or Hank’s Buffered Salt Solution (HBSS) by intratracheal aspiration (IA) at 12, 15 and 19 days after timed-breeding. All mated females received a booster exposure after pup weaning. Offspring: Pups (8 weeks old) from MACA-sensitized dams were exposed 3 times IA to homologous (MACA) or heterologous (house dust mite) allergen or HBSS. Serum and bronchoalveolar lavage fluid (BALF) were obtained from all mice 2 days after their final IA. RESULTS: Dams: MACA administration induced responses characteristic of allergic asthma regardless of pregnancy outcome. However, mice with failed pregnancies demonstrated higher BALF cellularity, protein levels, LDH activity and serum IgE than mice with successful deliveries. Offspring: Pups treated with either allergen displayed responses characteristic of allergic asthma. However, these responses were clearly enhanced in pups receiving heterologous allergen. CONCLUSIONS: Gestational allergen exposure may be associated with decreased maternal response to subsequent homologous allergen challenge, but enhanced offspring response to heterologous allergen. (Supported by UNC/EPA Cooperative Training Agreement CR83323701. This abstract does not reflect EPA policy.) Funding: UNC/EPA Cooperative Training Agreement CR83323701
694
Inhibition of Protein Binding in Hypersensitivity Pneumonitis with Pigeon Serum and Bird Excrement Extracts J. D. K. McNairn, F. Pacheco, J. M. Portnoy, C. Barnes; Children’s Mercy Hospital, Kansas City, MO. RATIONALE: Bird Fancier’s Disease (BFD), is a form of hypersensitivity pneumonitis (HP) caused by a variety of bird species. A goal of this project was to identify differences in protein content between avian serum samples and avian excrement samples as they relate to seroligic binding in BFD. METHODS: Cross-reactivity among bird species has been previously demonstrated. Serum of a patient with serologically and biopsy confirmed BFD was used in Western blot assays with commercially available pigeon (Columbiformes Columbidae) serum, and Sulphur-crested Cocktoo and African Grey Parrot droppings obtained from the actual pets using methods described elsewhere. After confirming protein binding between the patient’s serum and various avian samples (but not Micropolyspora faeni), patient serum was then inhibited with pigeon serum, pigeon excrement, Sulphur-crested cockatoo excrement or M faeni. RESULTS: Serologic binding was evident, with bands of multiple molecular weights. Inhibition with the M faeni showed no change in protein binding. Inhibition with the pigeon excrement showed complete inhibition. Pigeon serum showed near total inhibition aside from a faint high-molecular weight band in avian serum samples; however several high molecular weight bands remained in the excrement lanes. Inhibition with Sulphur-crested cockatoo excrement showed near complete inhibition of all bands within the Cockatoo lane; other avian serum lanes showed decreased binding; there appeared to be little change in the excrement lanes.
CONCLUSIONS: Pigeon excrement contains proteins in addition to those in avian serum, which show evidence of serologic binding in BFD. Additionally, Cockatoo excrement does not inhibt binding by several other avian species. Funding: Children’s Mercy Hospital
695
Maternal Bisphenol A (BPA) Exposure Induces Allergic Sensitization In Animal Model T. Midoro-Horiuti, R. Tiwari, I. Kobayashi, R. M. Goldblum; University of Texas Medical Branch, Galveston, TX. RATIONALE: We recently reported that estradiol and various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro. We hypothesized that these agents would enhance allergic sensitization as well as responsiveness. To test this hypothesis we have exposed fetal mice to the common environmental estrogen BPA via maternal loading and assessed the pups’ response to allergic sensitization. METHODS: Female BALB/c mice received 10 mg/ml BPA in their drinking water from one week prior to impregnation to the end of the study. Infant mice were given one 5 mg of ovalbumin (OVA) with aluminum hydroxide intraperitoneally on day 4 and 3% OVA by nebulization for 10 min on days 13, 14 and 15. On day 17, serum IgE antibodies to OVA were assessed by ELISA and airway inflammation and hyperresponsiveness (AHR) by enumerating eosinophils (Eo) in bronchoalveolar lavage (BAL) fluid and whole body barometric plethysmography. RESULTS: Infants from BPA-exposed mother responded to this ‘‘suboptimal’’ sensitization with higher serum IgE anti-OVA concentrations, compared to infants from unexposed mothers (p < 0.05). Similarly eosinophilic inflammation of their airways (BAL Eos) was significantly greater. Finally, AHR of the OVA-sensitized infants from BPA-treated mothers was enhanced relative to the infants from mothers that were not exposed to BPA (p < 0.05). CONCLUSIONS: Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma. Whether there is a critical period/burden for this exposure remains to be elucidated. Funding: NIAID
MONDAY
693
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
Allergic Asthma and the Developing Immune System: A Pilot Study C. M. Pucheu-Haston1, L. B. Copeland2, M. D. W. Ward2; 1Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC, 2 National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC. RATIONALE: The predisposition towards atopic disease begins early in life, and the risk of developing asthma is heightened following prenatal exposure to some compounds. Nonetheless, the effect of gestational aeroallergen exposure on the developing immune system is unclear. Project objectives are 1) to develop an animal model of gestational aeroallergen exposure, 2) to determine the response of gestationallyexposed offspring to subsequent allergen exposure and 3) to determine the effects of allergen exposure during pregnancy on the development of maternal sensitization. METHODS: Dams: BALB/c mice received Metarhizium anisopliae extract (MACA) or Hank’s Buffered Salt Solution (HBSS) by intratracheal aspiration (IA) at 12, 15 and 19 days after timed-breeding. All mated females received a booster exposure after pup weaning. Offspring: Pups (8 weeks old) from MACA-sensitized dams were exposed 3 times IA to homologous (MACA) or heterologous (house dust mite) allergen or HBSS. Serum and bronchoalveolar lavage fluid (BALF) were obtained from all mice 2 days after their final IA. RESULTS: Dams: MACA administration induced responses characteristic of allergic asthma regardless of pregnancy outcome. However, mice with failed pregnancies demonstrated higher BALF cellularity, protein levels, LDH activity and serum IgE than mice with successful deliveries. Offspring: Pups treated with either allergen displayed responses characteristic of allergic asthma. However, these responses were clearly enhanced in pups receiving heterologous allergen. CONCLUSIONS: Gestational allergen exposure may be associated with decreased maternal response to subsequent homologous allergen challenge, but enhanced offspring response to heterologous allergen. (Supported by UNC/EPA Cooperative Training Agreement CR83323701. This abstract does not reflect EPA policy.) Funding: UNC/EPA Cooperative Training Agreement CR83323701
694
Inhibition of Protein Binding in Hypersensitivity Pneumonitis with Pigeon Serum and Bird Excrement Extracts J. D. K. McNairn, F. Pacheco, J. M. Portnoy, C. Barnes; Children’s Mercy Hospital, Kansas City, MO. RATIONALE: Bird Fancier’s Disease (BFD), is a form of hypersensitivity pneumonitis (HP) caused by a variety of bird species. A goal of this project was to identify differences in protein content between avian serum samples and avian excrement samples as they relate to seroligic binding in BFD. METHODS: Cross-reactivity among bird species has been previously demonstrated. Serum of a patient with serologically and biopsy confirmed BFD was used in Western blot assays with commercially available pigeon (Columbiformes Columbidae) serum, and Sulphur-crested Cocktoo and African Grey Parrot droppings obtained from the actual pets using methods described elsewhere. After confirming protein binding between the patient’s serum and various avian samples (but not Micropolyspora faeni), patient serum was then inhibited with pigeon serum, pigeon excrement, Sulphur-crested cockatoo excrement or M faeni. RESULTS: Serologic binding was evident, with bands of multiple molecular weights. Inhibition with the M faeni showed no change in protein binding. Inhibition with the pigeon excrement showed complete inhibition. Pigeon serum showed near total inhibition aside from a faint high-molecular weight band in avian serum samples; however several high molecular weight bands remained in the excrement lanes. Inhibition with Sulphur-crested cockatoo excrement showed near complete inhibition of all bands within the Cockatoo lane; other avian serum lanes showed decreased binding; there appeared to be little change in the excrement lanes.
CONCLUSIONS: Pigeon excrement contains proteins in addition to those in avian serum, which show evidence of serologic binding in BFD. Additionally, Cockatoo excrement does not inhibt binding by several other avian species. Funding: Children’s Mercy Hospital
695
Maternal Bisphenol A (BPA) Exposure Induces Allergic Sensitization In Animal Model T. Midoro-Horiuti, R. Tiwari, I. Kobayashi, R. M. Goldblum; University of Texas Medical Branch, Galveston, TX. RATIONALE: We recently reported that estradiol and various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro. We hypothesized that these agents would enhance allergic sensitization as well as responsiveness. To test this hypothesis we have exposed fetal mice to the common environmental estrogen BPA via maternal loading and assessed the pups’ response to allergic sensitization. METHODS: Female BALB/c mice received 10 mg/ml BPA in their drinking water from one week prior to impregnation to the end of the study. Infant mice were given one 5 mg of ovalbumin (OVA) with aluminum hydroxide intraperitoneally on day 4 and 3% OVA by nebulization for 10 min on days 13, 14 and 15. On day 17, serum IgE antibodies to OVA were assessed by ELISA and airway inflammation and hyperresponsiveness (AHR) by enumerating eosinophils (Eo) in bronchoalveolar lavage (BAL) fluid and whole body barometric plethysmography. RESULTS: Infants from BPA-exposed mother responded to this ‘‘suboptimal’’ sensitization with higher serum IgE anti-OVA concentrations, compared to infants from unexposed mothers (p < 0.05). Similarly eosinophilic inflammation of their airways (BAL Eos) was significantly greater. Finally, AHR of the OVA-sensitized infants from BPA-treated mothers was enhanced relative to the infants from mothers that were not exposed to BPA (p < 0.05). CONCLUSIONS: Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma. Whether there is a critical period/burden for this exposure remains to be elucidated. Funding: NIAID
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