Titanium salts tested in reconstructed human skin with integrated MUTZ-3-derived Langerhans cells show an irritant rather than a sensitizing potential.

Contact Dermatitis
Charlotte T Rodrigues NevesSusan Gibbs

Abstract

The nature of clinically related adverse reactions to titanium is still unknown. To determine whether titanium salts have irritant or sensitizing potential in a reconstructed human skin (RHS) model with integrated Langerhans cells (LCs). 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. 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. These results...Continue Reading

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Citations

Oct 30, 2021·Contact Dermatitis·Michele BuonomoSara Hylwa

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Methods Mentioned

BETA
Assay
biopsies
flow cytometry
FACS
PCR
flow
ELISA

Software Mentioned

GraphPad Prism
GraphPad
Elements
CellQuest Pro
CellQuest Pro FACS
NIS

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