PMID- 22245253
OWN - NLM
STAT- MEDLINE
DCOM- 20120416
LR  - 20131121
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 209
IP  - 3
DP  - 2012 Mar 25
TI  - B cell increases and ex vivo IL-2 production as secondary endpoints for the 
      detection of sensitizers in non-radioisotopic local lymph node assay using flow 
      cytometry.
PG  - 255-63
LID - 10.1016/j.toxlet.2011.12.012 [doi]
AB  - Non-radioisotopic local lymph node assay (LLNA) using 5-bromo-2'-deoxyuridine 
      (BrdU) with flow cytometry (FCM) is gaining attention since it is free from the 
      regulatory issues in traditional LLNA (tLLNA) accompanying in vivo uses of 
      radioisotope, (3)H-thymidine. However, there is also concern over compromised 
      performance of non-radioisotopic LLNA, raising needs for additional endpoints to 
      improve the accuracy. With the full 22 reference substances enlisted in OECD Test 
      Guideline No. 429, we evaluated the performance of LLNA:BrdU-FCM along with the 
      concomitant measurements of B/T cell ratio and ex vivo cytokine production from 
      isolated lymph node cells (LNCs) to examine the utility of these markers as 
      secondary endpoints. Mice (Balb/c, female) were topically treated with substances 
      on both ears for 3 days and then, BrdU was intraperitoneally injected on day 5. 
      After a day, lymph nodes were isolated and undergone FCM to determine BrdU 
      incorporation and B/T cell sub-typing with B220+ and CD3e+. Ex vivo cytokine 
      production by LNCs was measured such as IL-2, IL-4, IL-6, IL-12, IFN-gamma, MCP-1, 
      GM-CSF and TNFalpha. Mice treated with sensitizers showed preferential increases in B 
      cell population and the selective production of IL-2, which matched well with the 
      increases in BrdU incorporation. When compared with guinea pig or human data, 
      BrdU incorporation, B cell increase and IL-2 production ex vivo could 
      successfully identify sensitizers with the accuracy comparable to tLLNA, 
      suggesting that these markers may be useful for improving the accuracy of 
      LLNA:BrdU-FCM or as stand-alone non-radioisotopic endpoints.
CI  - Copyright A(c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Jung, Kyoung-Mi
AU  - Jung KM
AD  - Medical Beauty Research Institute, Amorepacific CO R&D Center, Republic of Korea.
FAU - Jang, Won-Hee
AU  - Jang WH
FAU - Lee, Yong-Kyoung
AU  - Lee YK
FAU - Yum, Young Na
AU  - Yum YN
FAU - Sohn, Soojung
AU  - Sohn S
FAU - Kim, Bae-Hwan
AU  - Kim BH
FAU - Chung, Jin-Ho
AU  - Chung JH
FAU - Park, Young-Ho
AU  - Park YH
FAU - Lim, Kyung-Min
AU  - Lim KM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120102
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Allergens)
RN  - 0 (Interleukin-2)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - *Allergens/immunology/pharmacology
MH  - Animals
MH  - B-Lymphocytes/*cytology/immunology
MH  - Bromodeoxyuridine/metabolism
MH  - Cells, Cultured
MH  - Data Interpretation, Statistical
MH  - Dermatitis, Allergic Contact
MH  - Endpoint Determination
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - *Flow Cytometry
MH  - Guinea Pigs
MH  - Humans
MH  - Interleukin-2/*biosynthesis/immunology
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/cytology/*immunology
MH  - Lymphocyte Count
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Predictive Value of Tests
MH  - Sensitivity and Specificity
MH  - Species Specificity
MH  - T-Lymphocytes/cytology/immunology
EDAT- 2012/01/17 06:00
MHDA- 2012/04/17 06:00
CRDT- 2012/01/17 06:00
PHST- 2011/07/08 00:00 [received]
PHST- 2011/12/22 00:00 [revised]
PHST- 2011/12/23 00:00 [accepted]
PHST- 2012/01/17 06:00 [entrez]
PHST- 2012/01/17 06:00 [pubmed]
PHST- 2012/04/17 06:00 [medline]
AID - S0378-4274(11)01673-0 [pii]
AID - 10.1016/j.toxlet.2011.12.012 [doi]
PST - ppublish
SO  - Toxicol Lett. 2012 Mar 25;209(3):255-63. doi: 10.1016/j.toxlet.2011.12.012. Epub 
      2012 Jan 2.