Abstract
We revealed in previous studies that nitration of food proteins reduces the risk of de novo sensitization in a murine food allergy model. In contrast, in situations with preformed specific IgE antibodies, in vitro experiments suggested an increased capacity of effector cell activation by nitrated food proteins.
Objective
The aim of this study was to investigate the influence of protein nitration on the effector phase of food allergy.
Design
BALB/c mice were immunized intraperitoneally (i.p.) with the milk allergen β-lactoglobulin (BLG) or the egg allergen ovomucoid (OVM), followed by intragastric (i.g.) gavages to induce a strong local inflammatory response and allergen-specific antibodies. Subsequently, naïve and allergic mice were intravenously (i.v.) challenged with untreated, sham-nitrated or nitrated BLG or OVM. Anaphylaxis was monitored by measuring core body temperature and determination of mouse mast cell protease-1 (mMCP-1) levels in blood.
Results
A significant drop of body temperature accompanied with significantly elevated concentrations of the anaphylaxis marker mMCP-1 were only observed in BLG allergic animals challenged with nitrated BLG and not in OVM allergic mice challenged with nitrated OVM. SDS-PAGE and circular dichroism analysis of the differentially modified allergens revealed an effect of nitration on the secondary protein structure exclusively for BLG together with enhanced protein aggregation.
Conclusion
Our data suggest that nitration affects differently the food allergens BLG and OVM. In the case of BLG, structural changes favored dimerization possibly explaining the increased anaphylactic reactivity in BLG allergic animals. © 2015 Diesner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
| Original language | English |
|---|---|
| Pages (from-to) | e0126279 |
| Journal | PLoS ONE |
| Volume | 10 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2015 |
Keywords
- antibody
- beta lactoglobulin
- chymase
- ovomucoid
- allergen
- Ccl2 protein, mouse
- lactoglobulin
- monocyte chemotactic protein 1
- nitrogen
- anaphylaxis
- animal cell
- animal experiment
- antibody response
- Article
- circular dichroism
- controlled study
- core temperature
- cytokine production
- female
- food allergy
- immunization
- in vivo study
- mouse
- nitration
- nonhuman
- oligomerization
- polyacrylamide gel electrophoresis
- protein aggregation
- protein secondary structure
- animal
- blood
- body temperature
- chemistry
- disease model
- drug effects
- egg allergy
- immunology
- intraperitoneal drug administration
- milk allergy
- molecular model
- procedures
- Allergens
- Anaphylaxis
- Animals
- Body Temperature
- Chemokine CCL2
- Circular Dichroism
- Disease Models, Animal
- Egg Hypersensitivity
- Immunization
- Injections, Intraperitoneal
- Lactoglobulins
- Mice
- Milk Hypersensitivity
- Models, Molecular
- Nitrogen
- Ovomucin
- Protein Structure, Secondary
Classification according to Österreichische Systematik der Wissenschaftszweige (ÖFOS 2012)
- 303012 Health sciences
Applied Research Level (ARL)
- Not applicable
Research focus/foci
- Applied Health Innovation
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In: PLoS ONE, Vol. 10, No. 5, 2015, p. e0126279.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Nitration of β-Lactoglobulin but Not of Ovomucoid Enhances Anaphylactic Responses in Food Allergic Mice
AU - Diesner, S.C.
AU - Schultz, C.
AU - Ackaert, C.
AU - Oostingh, G.J.
AU - Ondracek, A.
AU - Stremnitzer, C.
AU - Singer, J.
AU - Heiden, D.
AU - Roth-Walter, F.
AU - Fazekas, J.
AU - Assmann, V.E.
AU - Jensen-Jarolim, E.
AU - Stutz, H.
AU - Duschl, A.
AU - Untersmayr, E.
N1 - Cited By :12 Export Date: 14 December 2023 CODEN: POLNC Chemicals/CAS: beta lactoglobulin, 9045-23-2; chymase, 75496-62-7, 97501-92-3; nitrogen, 7727-37-9; Allergens; Ccl2 protein, mouse; Chemokine CCL2; Lactoglobulins; Nitrogen; Ovomucin Funding details: Austrian Science Fund, FWF, CCHD W1205-B09, SFB F4606-B19 Funding details: Kommission zur Förderung der wissenschaftlichen Forschung, KWF Funding text 1: This work was supported by P21577-B11 (to EU), P22236-B13 (to GJO) and KLI284 (to EU) of the Austrian Science Fund FWF (Fonds zur Foerderung der wissenschaftlichen Forschung; www. fwf.ac.at) and the Award of the Viennese Economic Chamber 2014 (to EU, https://www.wko.at/Content. Node/Interessenvertretung/Aus-und-Weiterbildung/w/ Wirtschaftskammerpreis_2014.html). JS, CaS, and JF were supported by FWF grants CCHD W1205-B09 and EJJ additionally by SFB F4606-B19 (Fonds zur Foerderung der wissenschaftlichen Forschung; www.fwf.ac.at). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Anna Willensdorfer and Silke Schrom for excellent technical support as well as Dr. Thomas Eiwegger for critical scientific discussion. All authors have seen and approved the final version of the manuscript. References: Nwaru, B.I., Hickstein, L., Panesar, S.S., Muraro, A., Werfel, T., The epidemiology of food allergy in Europe: A systematic review and meta-analysis (2014) Allergy, 69, pp. 62-75. , PMID: 24205824; Nwaru, B.I., Hickstein, L., Panesar, S.S., Roberts, G., Muraro, A., Prevalence of common food allergies in Europe: A systematic review and meta-analysis (2014) Allergy, 69, pp. 992-1007. , PMID: 24816523; Sicherer, S.H., Sampson, H.A., Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment (2014) The Journal of Allergy and Clinical Immunology, 133, pp. 291-307. , quiz 308. 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PY - 2015
Y1 - 2015
N2 - Background We revealed in previous studies that nitration of food proteins reduces the risk of de novo sensitization in a murine food allergy model. In contrast, in situations with preformed specific IgE antibodies, in vitro experiments suggested an increased capacity of effector cell activation by nitrated food proteins. Objective The aim of this study was to investigate the influence of protein nitration on the effector phase of food allergy. Design BALB/c mice were immunized intraperitoneally (i.p.) with the milk allergen β-lactoglobulin (BLG) or the egg allergen ovomucoid (OVM), followed by intragastric (i.g.) gavages to induce a strong local inflammatory response and allergen-specific antibodies. Subsequently, naïve and allergic mice were intravenously (i.v.) challenged with untreated, sham-nitrated or nitrated BLG or OVM. Anaphylaxis was monitored by measuring core body temperature and determination of mouse mast cell protease-1 (mMCP-1) levels in blood. Results A significant drop of body temperature accompanied with significantly elevated concentrations of the anaphylaxis marker mMCP-1 were only observed in BLG allergic animals challenged with nitrated BLG and not in OVM allergic mice challenged with nitrated OVM. SDS-PAGE and circular dichroism analysis of the differentially modified allergens revealed an effect of nitration on the secondary protein structure exclusively for BLG together with enhanced protein aggregation. Conclusion Our data suggest that nitration affects differently the food allergens BLG and OVM. In the case of BLG, structural changes favored dimerization possibly explaining the increased anaphylactic reactivity in BLG allergic animals. © 2015 Diesner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
AB - Background We revealed in previous studies that nitration of food proteins reduces the risk of de novo sensitization in a murine food allergy model. In contrast, in situations with preformed specific IgE antibodies, in vitro experiments suggested an increased capacity of effector cell activation by nitrated food proteins. Objective The aim of this study was to investigate the influence of protein nitration on the effector phase of food allergy. Design BALB/c mice were immunized intraperitoneally (i.p.) with the milk allergen β-lactoglobulin (BLG) or the egg allergen ovomucoid (OVM), followed by intragastric (i.g.) gavages to induce a strong local inflammatory response and allergen-specific antibodies. Subsequently, naïve and allergic mice were intravenously (i.v.) challenged with untreated, sham-nitrated or nitrated BLG or OVM. Anaphylaxis was monitored by measuring core body temperature and determination of mouse mast cell protease-1 (mMCP-1) levels in blood. Results A significant drop of body temperature accompanied with significantly elevated concentrations of the anaphylaxis marker mMCP-1 were only observed in BLG allergic animals challenged with nitrated BLG and not in OVM allergic mice challenged with nitrated OVM. SDS-PAGE and circular dichroism analysis of the differentially modified allergens revealed an effect of nitration on the secondary protein structure exclusively for BLG together with enhanced protein aggregation. Conclusion Our data suggest that nitration affects differently the food allergens BLG and OVM. In the case of BLG, structural changes favored dimerization possibly explaining the increased anaphylactic reactivity in BLG allergic animals. © 2015 Diesner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
KW - antibody
KW - beta lactoglobulin
KW - chymase
KW - ovomucoid
KW - allergen
KW - Ccl2 protein, mouse
KW - lactoglobulin
KW - monocyte chemotactic protein 1
KW - nitrogen
KW - anaphylaxis
KW - animal cell
KW - animal experiment
KW - antibody response
KW - Article
KW - circular dichroism
KW - controlled study
KW - core temperature
KW - cytokine production
KW - female
KW - food allergy
KW - immunization
KW - in vivo study
KW - mouse
KW - nitration
KW - nonhuman
KW - oligomerization
KW - polyacrylamide gel electrophoresis
KW - protein aggregation
KW - protein secondary structure
KW - animal
KW - blood
KW - body temperature
KW - chemistry
KW - disease model
KW - drug effects
KW - egg allergy
KW - immunology
KW - intraperitoneal drug administration
KW - milk allergy
KW - molecular model
KW - procedures
KW - Allergens
KW - Anaphylaxis
KW - Animals
KW - Body Temperature
KW - Chemokine CCL2
KW - Circular Dichroism
KW - Disease Models, Animal
KW - Egg Hypersensitivity
KW - Immunization
KW - Injections, Intraperitoneal
KW - Lactoglobulins
KW - Mice
KW - Milk Hypersensitivity
KW - Models, Molecular
KW - Nitrogen
KW - Ovomucin
KW - Protein Structure, Secondary
U2 - 10.1371/journal.pone.0126279
DO - 10.1371/journal.pone.0126279
M3 - Article
SN - 1932-6203
VL - 10
SP - e0126279
JO - PLoS ONE
JF - PLoS ONE
IS - 5
ER -