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Title: Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen

Abstract

Human peripheral blood-derived dendritic cells (DC) respond to a variety of chemical allergens by up-regulating expression of the co-stimulatory molecule CD86. It has been postulated that this measure might provide the basis for an in vitro alternative approach for the identification of skin sensitizing chemicals. We recently reported that DC, exposed in culture to the highest non-cytotoxic concentrations of various chemical allergens, displayed marginal up-regulation of membrane CD86 expression; the interpretation being that such changes were insufficiently sensitive for the purposes of hazard identification. For the work presented here, immature DC were derived from human monocytes and treated with the chemical allergens 2,4-dinitrobenzenesulfonic acid (DNBS), nickel sulfate (NiSO{sub 4}), p-phenylenediamine (PPD), Bandrowski's base (BB), hydroquinone (HQ) and propyl gallate (PG) for 48 h at concentrations which induced both no to slight to moderate cytotoxicity. For comparison, DC were treated with the irritants sodium dodecyl sulfate (SDS), benzoic acid (BA), and benzalkonium chloride (BZC) at concentrations resulting in comparable levels of cytotoxicity. CD86 expression, as measured by flow cytometry, was consistently up-regulated (ranging from 162 to 386% control) on DC treated with concentrations of chemical allergens that induced approximately 10-15% cytotoxicity. The irritants BA and BZC did not induce up-regulation ofmore » CD86 expression when tested at concentrations that induced similar levels of cytotoxicity. SDS, however, up-regulated CD86 expression to 125-138% of control in 2/4 preparations when tested at concentrations which induced similar toxicity. Our results confirm that chemical allergens up-regulate CD86 expression on blood-derived DC and illustrate further that up-regulation of CD86 surface marker expression is more robust when DC are treated with concentrations of chemical allergen that induce slight to moderate cytotoxicity.« less

Authors:
 [1];  [1];  [1];  [2]
  1. Procter and Gamble Company, Miami Valley Laboratories, PO Box 538707, Cincinnati, OH 45253-8707 (United States)
  2. Procter and Gamble Company, Miami Valley Laboratories, PO Box 538707, Cincinnati, OH 45253-8707 (United States). E-mail: gerberick.gf@pg.com
Publication Date:
OSTI Identifier:
20783379
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 209; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2005.03.019; PII: S0041-008X(05)00163-8; 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; BENZOIC ACID; CESIUM FLUORIDES; CHLORIDES; IN VITRO; MACROPHAGES; MONOCYTES; NICKEL SULFATES; SKIN; SODIUM; TOXICITY

Citation Formats

Hulette, Ben C., Ryan, Cindy A., Gildea, Lucy A., and Gerberick, G. Frank. Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.03.019.
Hulette, Ben C., Ryan, Cindy A., Gildea, Lucy A., & Gerberick, G. Frank. Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen. United States. doi:10.1016/j.taap.2005.03.019.
Hulette, Ben C., Ryan, Cindy A., Gildea, Lucy A., and Gerberick, G. Frank. Thu . "Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen". United States. doi:10.1016/j.taap.2005.03.019.
@article{osti_20783379,
title = {Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen},
author = {Hulette, Ben C. and Ryan, Cindy A. and Gildea, Lucy A. and Gerberick, G. Frank},
abstractNote = {Human peripheral blood-derived dendritic cells (DC) respond to a variety of chemical allergens by up-regulating expression of the co-stimulatory molecule CD86. It has been postulated that this measure might provide the basis for an in vitro alternative approach for the identification of skin sensitizing chemicals. We recently reported that DC, exposed in culture to the highest non-cytotoxic concentrations of various chemical allergens, displayed marginal up-regulation of membrane CD86 expression; the interpretation being that such changes were insufficiently sensitive for the purposes of hazard identification. For the work presented here, immature DC were derived from human monocytes and treated with the chemical allergens 2,4-dinitrobenzenesulfonic acid (DNBS), nickel sulfate (NiSO{sub 4}), p-phenylenediamine (PPD), Bandrowski's base (BB), hydroquinone (HQ) and propyl gallate (PG) for 48 h at concentrations which induced both no to slight to moderate cytotoxicity. For comparison, DC were treated with the irritants sodium dodecyl sulfate (SDS), benzoic acid (BA), and benzalkonium chloride (BZC) at concentrations resulting in comparable levels of cytotoxicity. CD86 expression, as measured by flow cytometry, was consistently up-regulated (ranging from 162 to 386% control) on DC treated with concentrations of chemical allergens that induced approximately 10-15% cytotoxicity. The irritants BA and BZC did not induce up-regulation of CD86 expression when tested at concentrations that induced similar levels of cytotoxicity. SDS, however, up-regulated CD86 expression to 125-138% of control in 2/4 preparations when tested at concentrations which induced similar toxicity. Our results confirm that chemical allergens up-regulate CD86 expression on blood-derived DC and illustrate further that up-regulation of CD86 surface marker expression is more robust when DC are treated with concentrations of chemical allergen that induce slight to moderate cytotoxicity.},
doi = {10.1016/j.taap.2005.03.019},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 209,
place = {United States},
year = {Thu Dec 01 00:00:00 EST 2005},
month = {Thu Dec 01 00:00:00 EST 2005}
}
  • The detection of the sensitizing potential of chemicals is of great importance to industry. A promising in vitro alternative to the currently applied animal assays for sensitization testing makes use of dendritic cells (DCs) that have the capability to process and present antigens to naive T cells and induce their proliferation. Here, we studied changes in gene expression profiles after exposing DCs to the contact allergen nickel sulfate. CD34+-progenitor-derived DCs, initiated from 3 different donors, were exposed to 60 {mu}M nickel sulfate, during 0.5, 1, 3, 6, 12 and 24 h. cDNA microarrays were used to assess the transcriptional activitymore » of about 11,000 genes. Significant changes in the expression of 283 genes were observed; 178 genes were up-regulated and 93 down-regulated. These genes were involved in metabolism, cell structure, immune response, transcription, signal transduction, transport, and apoptosis. No functional information was found for 74 genes. Real-time RT-PCR was used to confirm the microarray results of 12 genes. In addition, 3 DC maturation markers not present on the microarrays (DEC205, DC LAMP and CCR7) were analyzed using real-time RT-PCR and found to be up-regulated at several time points. Our data indicate that a broad range of biological processes is influenced by nickel. Some processes are clearly linked to the immune response and DC maturation, others may indicate a toxic effect of nickel.« less
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