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Title: The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

Abstract

Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells maymore » represent a valuable in vitro model for the screening of potential sensitizers.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [1];  [3]
  1. AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France)
  2. Laboratoire de Toxicologie, Faculte de Pharmacie (UM1), 15 av Charles Flahault, BP 14491, 34093 Montpellier Cedex 5 (France)
  3. AFSSAPS, Unite BCM, 635 Rue de la Garenne, 34740 Vendargues (France). E-mail: jean-claude.ourlin@afssaps.sante.fr
Publication Date:
OSTI Identifier:
20783449
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 212; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2005.06.018; PII: S0041-008X(05)00383-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL CELLS; CELL CULTURES; IN VITRO; LYMPH NODES; PERFORMANCE; POLYMERASE CHAIN REACTION; SCREENING; SENSITIZERS; SKIN

Citation Formats

Azam, Philippe, Peiffer, Jean-Luc, Chamousset, Delphine, Tissier, Marie-Helene, Bonnet, Pierre-Antoine, Vian, Laurence, Fabre, Isabelle, and Ourlin, Jean-Claude. The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.06.018.
Azam, Philippe, Peiffer, Jean-Luc, Chamousset, Delphine, Tissier, Marie-Helene, Bonnet, Pierre-Antoine, Vian, Laurence, Fabre, Isabelle, & Ourlin, Jean-Claude. The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers. United States. doi:10.1016/j.taap.2005.06.018.
Azam, Philippe, Peiffer, Jean-Luc, Chamousset, Delphine, Tissier, Marie-Helene, Bonnet, Pierre-Antoine, Vian, Laurence, Fabre, Isabelle, and Ourlin, Jean-Claude. Sat . "The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers". United States. doi:10.1016/j.taap.2005.06.018.
@article{osti_20783449,
title = {The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers},
author = {Azam, Philippe and Peiffer, Jean-Luc and Chamousset, Delphine and Tissier, Marie-Helene and Bonnet, Pierre-Antoine and Vian, Laurence and Fabre, Isabelle and Ourlin, Jean-Claude},
abstractNote = {Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers.},
doi = {10.1016/j.taap.2005.06.018},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 212,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 2006},
month = {Sat Apr 01 00:00:00 EST 2006}
}