PMID- 19150643
OWN - NLM
STAT- MEDLINE
DCOM- 20090420
LR  - 20131121
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 257
IP  - 3
DP  - 2009 Mar 29
TI  - Increased cell proliferation in spleen and lymph nodes peripheral to contact 
      allergen application site.
PG  - 113-6
LID - 10.1016/j.tox.2008.12.019 [doi]
AB  - The local lymph node assay (LLNA) is widely used to identify chemicals that are 
      contact sensitizers. The assay involves dosing mice with the chemical on both 
      ears and pooling the superficial parotid lymph nodes for assessment of lymphocyte 
      proliferation as a marker of sensitization. The present study explored potential 
      reduction in animal usage by dosing one ear with the allergen and the other with 
      vehicle-only. The respective draining lymph nodes were processed separately for 
      tritiated thymidine ((3)H-TdR) incorporation. Cell proliferation in proper 
      axillary and renal nodes, as well as in the spleen was also assessed. 
      Cross-contamination of the chemicals from the dosed ears to other parts of the 
      body via preening was prevented by dosing restrained animals and washing off the 
      residual chemical with saline after 4h. Dosing the left ear with 0.02% oxazolone 
      (OX) on unrestrained animals resulted in marked cell proliferation in its 
      draining lymph node (stimulation index, SI=12.8) and in the lymph node draining 
      the contra-lateral vehicle-dosed ear (SI=6), as well as the proper axillary lymph 
      nodes (SI=3.3). Increased (3)H-TdR incorporation was not observed in the renal 
      lymph nodes (SI=1.1). Similar stimulation of cells was observed in the lymph node 
      draining the ear contra-lateral to the 30% hexylcinnamaldehyde (HCA)-dosed ear. 
      Increased proliferative activity was observed in contra-lateral draining lymph 
      nodes of restrained mice demonstrating that these results cannot be attributed to 
      cross-contamination of adjacent skin. A significant increase in proliferation of 
      splenocytes was also observed. It is concluded that dermal application of a 
      contact allergen, as exemplified by OX and HCA, may induce cell proliferation in 
      the neighboring lymph nodes and spleen indicative of hapten and/or haptenated 
      proteins diffusing through the skin to peripheral nodes and the blood to produce 
      systemic sensitization. It is also possible that lymphatic capillaries may 
      communicate between the left and right side of the mouse head. Thus the 
      contra-lateral draining superficial parotid node cannot be used as a control for 
      application of contact allergen to a single ear in a modified LLNA.
FAU - Chipinda, Itai
AU  - Chipinda I
AD  - Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, 
      National Institute for Occupational Safety and Health, 1095 Willowdale Road, 
      Morgantown, WV 26505-2888, United States. IChipinda@cdc.gov
FAU - Anderson, Stacey E
AU  - Anderson SE
FAU - Butterworth, Leon F
AU  - Butterworth LF
FAU - Beezhold, Donald
AU  - Beezhold D
FAU - Siegel, Paul D
AU  - Siegel PD
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20081230
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Allergens)
RN  - 15646-46-5 (Oxazolone)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Allergens/*toxicity
MH  - Animals
MH  - Cell Proliferation/*drug effects
MH  - Dermatitis, Contact/*pathology
MH  - Female
MH  - Local Lymph Node Assay
MH  - Lymph Nodes/*pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oxazolone/pharmacology
MH  - Spleen/*pathology
MH  - Terminology as Topic
MH  - Thymidine/pharmacology
EDAT- 2009/01/20 09:00
MHDA- 2009/04/21 09:00
CRDT- 2009/01/20 09:00
PHST- 2008/12/03 00:00 [received]
PHST- 2008/12/15 00:00 [revised]
PHST- 2008/12/16 00:00 [accepted]
PHST- 2009/01/20 09:00 [entrez]
PHST- 2009/01/20 09:00 [pubmed]
PHST- 2009/04/21 09:00 [medline]
AID - S0300-483X(08)00609-4 [pii]
AID - 10.1016/j.tox.2008.12.019 [doi]
PST - ppublish
SO  - Toxicology. 2009 Mar 29;257(3):113-6. doi: 10.1016/j.tox.2008.12.019. Epub 2008 
      Dec 30.