Nitration of the egg-allergen ovalbumin enhances protein allergenicity but reduces the risk for oral sensitization in a murine model of food allergy
| Autor: | Ulrich Pöschl, Gertie Janneke Oostingh, Erika Jensen-Jarolim, Regina Knittelfelder, Susanne C. Diesner, Otto Scheiner, Elisabeth Förster-Waldl, Cornelia Schultz, Philipp Starkl, Yingyi Zhang, Albert Duschl, Kathrin Selzle, Durga Krishnamurthy, Tobias Pfaller, Eva Untersmayr, Arnold Pollak |
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| Rok vydání: | 2010 |
| Předmět: |
Allergy
lcsh:Medicine Immunoglobulin E medicine.disease_cause Epitope Epitopes Mice Allergen Tandem Mass Spectrometry Biochemistry/Protein Chemistry Allergies Enzyme-linked immunoassays lcsh:Science Sensitization Chromatography High Pressure Liquid Mice Inbred BALB C Multidisciplinary Smog biology Chemistry Immunogenicity medicine.anatomical_structure Female Immunology/Allergy and Hypersensitivity Food Hypersensitivity Research Article Nitration Nitrogen Ovalbumin Molecular Sequence Data Antibodies Food allergy Air Pollution Immune suppression medicine Animals Amino Acid Sequence Inflammation lcsh:R Allergens medicine.disease Disease Models Animal Food allergies Immunoglobulin G Immunology Immunology/Immune Response biology.protein Tyrosine lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 12, p e14210 (2010) |
| ISSN: | 1932-6203 |
| Popis: | Background: Nitration of proteins on tyrosine residues, which can occur due to polluted air under “summer smog” conditions, has been shown to increase the allergic potential of allergens. Since nitration of tyrosine residues is also observed during inflammatory responses, this modification could directly influence protein immunogenicity and might therefore contribute to food allergy induction. In the current study we have analyzed the impact of protein nitration on sensitization via the oral route. Methodology/Principal Findings: BALB/c mice were immunized intragastrically by feeding untreated ovalbumin (OVA), sham-nitrated ovalbumin (snOVA) or nitrated ovalbumin (nOVA) with or without concomitant acid-suppression. To analyze the impact of the sensitization route, the allergens were also injected intraperitoneally. Animals being fed OVA or snOVA under acid-suppressive medication developed significantly elevated levels of IgE, and increased titers of specific IgG1 and IgG2a antibodies. Interestingly, oral immunizations of nOVA under anti-acid treatment did not result in IgG and IgE formation. In contrast, intraperitoneal immunization induced high levels of OVA specific IgE, which were significantly increased in the group that received nOVA by injection. Furthermore, nOVA triggered significantly enhanced mediator release from RBL cells passively sensitized with sera from allergic mice. Gastric digestion experiments demonstrated protein nitration to interfere with protein stability as nOVA was easily degraded, whereas OVA and snOVA remained stable up to 120 min. Additionally, HPLC-chip-MS/MS analysis showed that one tyrosine residue (Y107) being very efficiently nitrated is part of an ovalbumin epitope recognized exclusively after oral sensitization. Conclusions/Significance: These data indicated that despite the enhanced triggering capacity in existing allergy, nitration of OVA may be associated with a reduced de novo sensitizing capability via the oral route due to enhanced protein digestibility and/or changes in antibody epitopes. 21577-B11 APW01205FW (VLID)2200635 |
| Databáze: | OpenAIRE |
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