PMID- 25469456
OWN - NLM
STAT- MEDLINE
DCOM- 20160513
LR  - 20150813
IS  - 1547-6901 (Electronic)
IS  - 1547-691X (Linking)
VI  - 12
IP  - 4
DP  - 2015
TI  - Characterization of the draining lymph node response in the mouse drug allergy 
      model: A model for drug hypersensitivity reactions.
PG  - 376-84
LID - 10.3109/1547691X.2014.988308 [doi]
AB  - The mouse drug allergy model (MDAM) was developed as a tool to predict the 
      potential of systemically administered drugs to produce hypersensitivity 
      reactions (HR). Drugs associated with HR in the clinic produce a marked increase 
      in the cellularity of the draining lymph nodes (DLN) in the MDAM. The objective 
      of this study was to characterize the changes in the DLN following exposure to 
      drugs associated with HR and to investigate whether lymphocyte migration and/or 
      proliferation play a role in the response. These endpoints were also investigated 
      in the local lymph node assay (LLNA) to determine whether responses between the 
      two assays occur via similar mechanisms. Results demonstrated that total numbers 
      of T- and B-cells were proportionally increased in the DLN of mice treated with 
      positive control drugs (i.e. abacavir, amoxicillin, ofloxacin, and 
      sulfamethoxazole) compared to animals administered the vehicle or negative 
      control drugs (metformin and cimetidine). In contrast, a significant increase in 
      the B-cell population of the DLN was observed for 2,4-dinitrofluorobenzene (DNFB) 
      following the LLNA protocol. Down-regulation of CD62L and up-regulation of CCR7 
      were observed for T-cells from the DLN of the positive control treated mice in 
      the MDAM, but not with DNFB in the LLNA. A mild increase in T-cell proliferation 
      was observed in the MDAM with positive control drugs, while DNFB in the LLNA 
      induced proliferation within the B-cell population only. Anti-CD40L antibody 
      administration inhibited MDAM responses to positive control drugs, but did not 
      affect DNFB-induced increases in total cell number in the LLNA. These results 
      suggest that the increased cellularity of the DLN in the MDAM may be the result 
      of drug-induced alterations in lymphocyte migration and/or effects on lymphocyte 
      proliferation. Moreover, it appears that different mechanisms may be involved in 
      driving the MDAM and LLNA responses.
FAU - Zhu, Xu
AU  - Zhu X
AD  - Immunotoxicology CoE, Drug Safety Research and Development, Pfizer Inc. , Groton, 
      CT , USA.
FAU - Cole, Susan H
AU  - Cole SH
FAU - Kawabata, Thomas T
AU  - Kawabata TT
FAU - Whritenour, Jessica
AU  - Whritenour J
LA  - eng
PT  - Journal Article
DEP - 20141203
PL  - England
TA  - J Immunotoxicol
JT  - Journal of immunotoxicology
JID - 101201960
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Receptors, CCR7)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/*immunology/pathology
MH  - *Cell Proliferation
MH  - Disease Models, Animal
MH  - Drug Hypersensitivity/*immunology/pathology
MH  - Female
MH  - Lymph Nodes/*immunology/pathology
MH  - Mice
MH  - Receptors, CCR7/immunology
MH  - T-Lymphocytes/*immunology/pathology
MH  - Up-Regulation/drug effects/immunology
OTO - NOTNLM
OT  - CCR7
OT  - CD62L
OT  - LLNA
OT  - drug hypersensitivity
OT  - flow cytometry
OT  - lymph nodes
OT  - mouse drug allergy model
EDAT- 2014/12/04 06:00
MHDA- 2016/05/14 06:00
CRDT- 2014/12/04 06:00
PHST- 2014/12/04 06:00 [entrez]
PHST- 2014/12/04 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
AID - 10.3109/1547691X.2014.988308 [doi]
PST - ppublish
SO  - J Immunotoxicol. 2015;12(4):376-84. doi: 10.3109/1547691X.2014.988308. Epub 2014 
      Dec 3.