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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
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 epi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689826/ https://www.ncbi.nlm.nih.gov/pubmed/32677096 http://dx.doi.org/10.1111/cod.13666 |
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author | Rodrigues Neves, Charlotte T. Spiekstra, Sander W. de Graaf, Niels P. J. Rustemeyer, Thomas Feilzer, Albert J. Kleverlaan, Cees J. Gibbs, Susan |
author_facet | Rodrigues Neves, Charlotte T. Spiekstra, Sander W. de Graaf, Niels P. J. Rustemeyer, Thomas Feilzer, Albert J. Kleverlaan, Cees J. Gibbs, Susan |
author_sort | Rodrigues Neves, Charlotte T. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7689826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-76898262020-12-05 Titanium salts tested in reconstructed human skin with integrated MUTZ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential Rodrigues Neves, Charlotte T. Spiekstra, Sander W. de Graaf, Niels P. J. Rustemeyer, Thomas Feilzer, Albert J. Kleverlaan, Cees J. Gibbs, Susan Contact Dermatitis Original Articles 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. Blackwell Publishing Ltd 2020-08-06 2020-11 /pmc/articles/PMC7689826/ /pubmed/32677096 http://dx.doi.org/10.1111/cod.13666 Text en © 2020 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Rodrigues Neves, Charlotte T. Spiekstra, Sander W. de Graaf, Niels P. J. Rustemeyer, Thomas Feilzer, Albert J. Kleverlaan, Cees J. Gibbs, Susan Titanium salts tested in reconstructed human skin with integrated MUTZ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential |
title | Titanium salts tested in reconstructed human skin with integrated MUTZ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential |
title_full | Titanium salts tested in reconstructed human skin with integrated MUTZ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential |
title_fullStr | Titanium salts tested in reconstructed human skin with integrated MUTZ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential |
title_full_unstemmed | Titanium salts tested in reconstructed human skin with integrated MUTZ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential |
title_short | Titanium salts tested in reconstructed human skin with integrated MUTZ‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential |
title_sort | titanium salts tested in reconstructed human skin with integrated mutz‐3‐derived langerhans cells show an irritant rather than a sensitizing potential |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689826/ https://www.ncbi.nlm.nih.gov/pubmed/32677096 http://dx.doi.org/10.1111/cod.13666 |
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