Description succincte
(Allemand)
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Es soll ein Maus-Modell etabliert werden, welches erlaubt, die Mechanismen der Kontaktsensibilisierung gegenüber kleinen Molekülen (Haptenen) zu untersuchen. Als Modell-Hapten wird FITC verwendet. Die Kenntnis dieser Mechanismen ist eine Grundvoraussetzung um ein in vitro Model zu entwickeln, in welchem das kontaktsensibilisierende Potential von Chemikalien überprüft werden kann
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Objectifs du projet
(Allemand)
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Es soll ein Maus-Modell etabliert werden, welches erlaubt, die Mechanismen der Kontaktsensibilisierung gegenüber kleinen Molekülen (Haptenen) zu untersuchen. Als Modell-Hapten wird FITC verwendet. Die Kenntnis dieser Mechanismen ist eine Grundvoraussetzung um ein in vitro Model zu entwickeln, in welchem das kontaktsensibilisierende Potential von Chemikalien überprüft werden kann
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Résumé des résultats (Abstract)
(Allemand)
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In conclusion, we can clearly confirm that substances which enhance penetration through the upper epidermal layers, such as detergents, enhance the risk for sensitization. However, it must be distinguished between positively and negatively charged detergents. Only the negatively charged detergents appear to enhance sensitization. The fact that such enhanced penetration through the epidermis leads to enhanced sensitization is not necessarily surprising and correlates with the clinical observation that contact dermatitis is usually an occupational disease in professions such as hair dressers, mechanics, and construction workers. In these professions, the skin is either in frequent in contact with detergents, or due to their “dirty work” these professionals have to frequently use detergents to wash their hands. The fact that simultaneous administration of certain chemical compounds known as strong irritants and strong contact sensitizers, such as DCP, enhances the risk for sensitization against other, less irritant and weaker contact sensitizers, as exemplified by FITC in our mouse model, has not been reported so far. From the basic immunological point of view, DCP acts as an “adjuvant” for epicutaneous sensitization. The mechanism of this adjuvant must be irritation of keratinocytes and consecutive activation of Langerhans cells to leave the epidermis. This would also explain, why nearly 100% of patients having skin contact with DCP develop contact hypersensitivity to this substance. The idea of this project was to improve tests used to predict the potential for contact sensitization to new small chemical compounds. In general, the classical way to test for the immunogenicity of allergenic potential of a substance is by injection of the substance to an animal. In all such tests adjuvants, typically alum, or others, is used. It is well known that injection of a compound alone, rarely induces an immune response. Testing of small chemical compounds to predict their potential for contact sensitization should not be different. These compounds should be applied using an adjuvant, such as SDS, DCP, for epicutaneous sensitization.
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