Modification and expulsion of keratins by human epidermal keratinocytes upon hapten exposure in vitro.
Artikel i vetenskaplig tidskrift, 2011

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.

Författare

Brigitte Bauer

Göteborgs universitet

Sofia Andersson

Göteborgs universitet

Anna-Lena Stenfeldt

Göteborgs universitet

Carl Simonsson

Göteborgs universitet

Jörgen Bergström

Göteborgs universitet

Marica B Ericson

Göteborgs universitet

Charlotte A Jonsson

Göteborgs universitet

Kerstin S Broo

Chemical Research in Toxicology

0893-228X (ISSN) 1520-5010 (eISSN)

Vol. 24 737-43

Ämneskategorier

Annan medicinsk grundvetenskap

Annan kemi

DOI

10.1021/tx200030y

PubMed

21486064