Abstract
BackgroundNitration 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 FindingsBALB/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/SignificanceThese 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.
Highlights
The prevalence of type I allergies is steadily increasing in Western societies [1]
A recent study has revealed that the allergenic potential of Bet v1 for inducing IgEdependent type 1 allergy is increased by protein nitration [11]
We investigated the location of nitrated tyrosine residues within the nitrated ovalbumin (nOVA) protein and evaluated the nitration degree of the tyrosine residues by HPLC-chip-MS/MS analysis
Summary
The prevalence of type I allergies is steadily increasing in Western societies [1]. A reduced exposure to microbial pathogens in childhood has been discussed to represent one of the major causes, summarized in the so-called hygiene hypothesis [2]. The components of smog, NO2 and O3, have been discussed to chemically alter airborne proteins, resulting in e.g. protein nitration. This effect has been demonstrated for Bet v1, the major birch pollen allergen, with was detected in nitrated form in dust samples from various urban environments [6]. A recent study has revealed that the allergenic potential of Bet v1 for inducing IgEdependent type 1 allergy is increased by protein nitration [11]. 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. In the current study we have analyzed the impact of protein nitration on sensitization via the oral route
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