PMID- 19665512
OWN - NLM
STAT- MEDLINE
DCOM- 20090923
LR  - 20211020
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 264
IP  - 1-2
DP  - 2009 Oct 1
TI  - A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict 
      contact allergenicity of chemicals.
PG  - 1-9
LID - 10.1016/j.tox.2009.07.021 [doi]
AB  - A predictive allergenicity test system for assessing the contact allergenicity of 
      chemicals is needed by the cosmetic and pharmaceutical industry to monitor 
      product safety in the marketplace. Development of such non-animal alternative 
      assay systems for skin sensitization and hazard identification has been pursued 
      by policy makers and regulatory agencies. We investigated whether phenotypic and 
      functional changes to a subset of dendritic cells (DC), plasmacytoid DC (pDC), 
      could be used to identify contact allergens. To achieve this goal, normal human 
      DC were generated from CD34+ progenitor cells and cryopreserved. Frozen DC were 
      thawed and the pDC fraction (CD123+/CD11c-) was harvested using FACS sorting. The 
      pDC were cultured, expanded, and exposed to chemical allergens (N=26) or 
      non-allergens (N=22). Concentrations of each chemical that resulted in >50% 
      viability was determined using FACS analysis of propidium iodide stained cells 
      using pDC from 2 to 5 donors. Expression of the surface marker, CD86, which has 
      been implicated in dendritic cell maturation, was used as a marker of 
      allergenicity. CD86 expression increased (> or =1.5-fold) for 25 of 26 allergens 
      (sensitivity=96%) but did not increase for 19 of 22 non-allergens 
      (specificity=86%). In a direct comparison to historical data for the regulatory 
      approved, mouse local lymph node assay (LLNA) for 23 allergens and 22 
      non-allergens, the pDC method had sensitivity and specificity of 96% and 86%, 
      respectively, while the sensitivity and specificity of the LLNA assay was 83% and 
      82%, respectively. In conclusion, CD86 expression in pDC appears to be a 
      sensitive and specific indicator to identify contact allergenicity. Such an assay 
      method utilizing normal human cells will be useful for high throughput screening 
      of chemicals for allergenicity.
CI  - 2009 Elsevier Ireland Ltd.
FAU - Ayehunie, Seyoum
AU  - Ayehunie S
AD  - MatTek Corporation, Ashland, MA 01721, United States. sayehunie@mattek.com
FAU - Snell, Maureen
AU  - Snell M
FAU - Child, Matthew
AU  - Child M
FAU - Klausner, Mitchell
AU  - Klausner M
LA  - eng
GR  - R43 CA106137-01/CA/NCI NIH HHS/United States
GR  - R43 CA106137/CA/NCI NIH HHS/United States
GR  - R44 CA106137-02A1/CA/NCI NIH HHS/United States
GR  - R44 CA106137/CA/NCI NIH HHS/United States
GR  - R44 CA106137-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090807
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Allergens)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD11 Antigens)
RN  - 0 (Coloring Agents)
RN  - 0 (Cosmetics)
RN  - 0 (Interleukin-3 Receptor alpha Subunit)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pharmaceutical Vehicles)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Allergens/chemistry/*toxicity
MH  - Animal Testing Alternatives
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Biological Assay
MH  - CD11 Antigens/*immunology
MH  - Cells, Cultured
MH  - Coloring Agents
MH  - Cosmetics/chemistry/*toxicity
MH  - Dendritic Cells/*drug effects
MH  - Dermatitis, Allergic Contact/*immunology
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Fetal Blood/cytology
MH  - Flow Cytometry
MH  - Humans
MH  - Interleukin-3 Receptor alpha Subunit/*immunology
MH  - Lipopolysaccharides/toxicity
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Pharmaceutical Vehicles
MH  - Reproducibility of Results
MH  - Tetrazolium Salts
MH  - Thiazoles
PMC - PMC2747095
MID - NIHMS137468
EDAT- 2009/08/12 09:00
MHDA- 2009/09/24 06:00
PMCR- 2010/10/01
CRDT- 2009/08/12 09:00
PHST- 2009/03/06 00:00 [received]
PHST- 2009/07/01 00:00 [revised]
PHST- 2009/07/02 00:00 [accepted]
PHST- 2009/08/12 09:00 [entrez]
PHST- 2009/08/12 09:00 [pubmed]
PHST- 2009/09/24 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - S0300-483X(09)00415-6 [pii]
AID - 10.1016/j.tox.2009.07.021 [doi]
PST - ppublish
SO  - Toxicology. 2009 Oct 1;264(1-2):1-9. doi: 10.1016/j.tox.2009.07.021. Epub 2009 
      Aug 7.