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Modification and expulsion of keratins by human epidermal keratinocytes upon hapten exposure in vitro.

Journal article
Authors Brigitte Bauer
Sofia Andersson
Anna-Lena Stenfeldt
Carl Simonsson
Jörgen Bergström
Marica B Ericson
Charlotte A Jonsson
Kerstin S Broo
Published in Chemical research in toxicology
Volume 24
Issue 5
Pages 737-43
ISSN 1520-5010
Publication year 2011
Published at Department of Chemistry
Core Facilities, Proteomics
Department of Physics (GU)
Pages 737-43
Language en
Links dx.doi.org/10.1021/tx200030y
Subject categories Other Chemistry Topics, Chemistry

Abstract

Allergic contact dermatitis is the most prevalent form of human immunotoxicity. It is caused by reactive low molecular weight chemicals, that is, haptens, coming in contact with the skin where hapten-peptide complexes are formed, activating the immune system. By using sensitizing fluorescent thiol-reactive haptens, that is, bromobimanes, we show how keratinocytes respond to hapten exposure in vitro and reveal, for the first time in a living system, an exact site of haptenation. Rapid internalization and reaction of haptens with keratin filaments were visualized. Subsequently, keratinocytes respond in vitro to hapten exposure by release of membrane blebs, which contain haptenated keratins 5 and 14. Particularly, cysteine 54 of K5 was found to be a specific target. A mechanism is proposed where neoepitopes, otherwise hidden from the immune system, are released after hapten exposure via keratinocyte blebbing. The observed expulsion of modified keratins by keratinocytes in vitro might play a role during hapten sensitization in vivo and should be subject to further investigations.

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