title: Nitration of the egg-allergen ovalbumin enhances protein allergenicity but reduces the risk for oral sensitization in a murine model of food allergy.
abstract: 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.
  
  
  RESULTS
  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 (Y(107)) being very efficiently nitrated is part of an ovalbumin epitope recognized exclusively after oral sensitization.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. eva.untersmayr@meduniwien.ac.at
authors.forename: Eva
authors.initials: E
authors.lastname: Untersmayr
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Diesner
authors.forename: Gertie Janneke
authors.initials: GJ
authors.lastname: Oostingh
authors.forename: Kathrin
authors.initials: K
authors.lastname: Selzle
authors.forename: Tobias
authors.initials: T
authors.lastname: Pfaller
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schultz
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Durga
authors.initials: D
authors.lastname: Krishnamurthy
authors.forename: Philipp
authors.initials: P
authors.lastname: Starkl
authors.forename: Regina
authors.initials: R
authors.lastname: Knittelfelder
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Förster-Waldl
authors.forename: Arnold
authors.initials: A
authors.lastname: Pollak
authors.forename: Otto
authors.initials: O
authors.lastname: Scheiner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pöschl
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
authors.forename: Albert
authors.initials: A
authors.lastname: Duschl
mesh_terms: D000397:Air Pollution; D000485:Allergens; D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005512:Food Hypersensitivity; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry*; D012905:Smog; D053719:Tandem Mass Spectrometry / Q000379:methods; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000485:Allergens; D000939:Epitopes; D007074:Immunoglobulin G; D012905:Smog; D007073:Immunoglobulin E; D014443:Tyrosine; D010047:Ovalbumin; D009584:Nitrogen