University of Oulu

Effect of heat denaturation of bovine milk beta-lactoglobulin on its epithelial transport and allergenicity

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Author: Rytkönen, Jani1,2,3,4
Organizations: 1University of Oulu, Faculty of Medicine, Department of Pathology
2University of Oulu, Faculty of Medicine, Department of Paediatrics
3University of Oulu, Kajaani University Consortium, Laboratory of Biotechnology
4Oulu University Hospital
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
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Language: English
Published: 2006
Publish Date: 2006-06-06
Thesis type: Doctoral Dissertation
Defence Note: Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of Valio in Sotkamo (Salmelantie 6) on June 16th, 2006, at 12 noon
Reviewer: Professor Thomas Haertlé
Docent Heli Majamaa


Beta-lactoglobulin (β-lg) is the main whey protein in bovine milk. It belongs to the lipocalin protein family, and it is one of the main milk allergens. Resistance to hydrolysis is a particular feature of β-lg making it possible that β-lg reaches the small intestine in its native form. Heat treatments during milk processing may change the native structure of bovine β-lg and change its intestinal transport properties. Heat induced conformational alterations may also expose new antigenic sites. However, there have been no previous studies on the effects of heat treatment on the transport of β-lg or on its sensitizing properties.

Cow’s milk allergy is one of the most important food allergies affecting about 2.4% of infants. Milk proteins, including β-lg, in breast milk substitute formulas are often the earliest foreign antigens in the diet of newborns. According to the hygiene hypothesis, natural infections and vaccinations may modify the immunological balance and decrease the risk of allergy.

Isoelectric precipitations followed by anion exchange and gel filtration were used to purify bovine milk β-lg in its native form. Transport of native and heat-denatured β-lg was compared in two in vitro cell models, Caco-2 and M-cells. Sensitization properties of native and heat-denatured β-lg were studied with an animal model using Hooded-Lister rats. Effects of BCG vaccination in combination with the native β-lg were also studied. Effects of different sensitizations were assessed by antibody levels in serum and inflammation locally in the gastrointestinal tract.

Heat denaturation of β-lg made its transport slower in both enterocytes and M-cells. M-cells were more effective transporters of both native and heat-denatured β-lg than caco-2 cells. Animals generated higher levels of IgE when sensitized with native β-lg, but heat-denatured β-lg induced a more intense inflammatory cell reaction in the gastrointestinal tract. Vaccination with BCG decreased serum IgE concentration and modified the predominant site of the inflammatory cell response in intestine.

The results indicate that, heat denaturation of β-lg and BCG vaccination, change both the systemic and the mucosal response to bovine milk β-lg. The reasons for this remain speculative. The effect of BCG vaccination is consistent with the hygiene hypothesis. The observed alteration of transport properties could be one mechanism by which heat denaturation modifies the allergenic properties of this protein, but additional studies are necessary to assess whether other mechanisms, such as exposure of new antigenic determinants are also relevant.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-8120-9
ISBN Print: 951-42-8119-5
Issue: 883
Copyright information: © University of Oulu, 2006. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.