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Titanium salts tested in reconstructed human skin with integrated MUTZ ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential
Author(s) -
Rodrigues Neves Charlotte T.,
Spiekstra Sander W.,
Graaf Niels P. J.,
Rustemeyer Thomas,
Feilzer Albert J.,
Kleverlaan Cees J.,
Gibbs Susan
Publication year - 2020
Publication title -
contact dermatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.524
H-Index - 96
eISSN - 1600-0536
pISSN - 0105-1873
DOI - 10.1111/cod.13666
Subject(s) - dermis , chemistry , human skin , epidermis (zoology) , titanium , irritant contact dermatitis , langerhans cell , chemokine , cd86 , microbiology and biotechnology , allergic contact dermatitis , immunology , biochemistry , allergy , pathology , biology , anatomy , medicine , immune system , phenotype , genetics , organic chemistry , gene , receptor
Background The nature of clinically related adverse reactions to titanium is still unknown. Objective To determine whether titanium salts have irritant or sensitizing potential in a reconstructed human skin (RHS) model with integrated Langerhans cells (LCs). Methods RHS‐LCs (ie, reconstructed epidermis) containing primary differentiated keratinocytes and CFSE + CD1a + ‐LCs generated from the MUTZ‐3 cell line on a primary fibroblast‐populated collagen hydrogel (dermis) were topically exposed to titanium(IV) bis(ammonium lactato)dihydroxide (TiALH). LC migration and plasticity were determined. Results TiALH resulted in CFSE + CD1a + ‐LC migration out of the epidermis. Neutralizing antibodies to CCL5 and CXCL12 showed that LC migration was CCL5 and not CXCL12 mediated. LCs accumulating within the dermis after TiALH exposure were CFSE + Lang + CD68 + which is characteristic of a phenotypic switch of MUTZ‐LC to a macrophage‐like cell. Furthermore, TiALH did not result in increased interleukin (IL)‐1β or CCR7 messenger RNA (mRNA) in the dermis, but did result in increased IL‐10 mRNA. In addition, monocultures of MUTZ‐LCs failed to increase LC maturation biomarkers CD83, CD86, and CXCL‐8 when exposed to noncytotoxic concentrations of four different titanium salts. Conclusion These results classify titanium salts as irritants rather than sensitizers and indicate that titanium implant‐related complaints could be due to localized irritant‐mediated inflammation arising from leachable agents rather than a titanium metal allergy.