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Increased cell proliferation in spleen and lymph nodes peripheral to contact allergen application site.

Authors
Chipinda-I; Anderson-SE; Butterworth-LF; Beezhold-D; Siegel-PD
Source
Toxicology 2009 Mar; 257(3):113-116
NIOSHTIC No.
20035118
Abstract
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 (3H-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 4 h. 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 3H-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.
Keywords
Animal-studies; Biological-effects; Biological-factors; Biological-monitoring; Blood-cells; Blood-sampling; Cell-biology; Cell-damage; Cell-function; Cell-growth; Cell-metabolism; Cellular-function; Cellular-reactions; Chemical-analysis; Chemical-composition; Chemical-hypersensitivity; Chemical-reactions; Ear-disorders; Ears; Laboratory-animals; Laboratory-testing; Lymph-nodes; Lymphatic-system; Physical-reactions; Risk-analysis; Skin; Skin-absorption; Skin-exposure; Skin-sensitivity; Spleen-disorders; Splenic-tissue; Biomarkers; Blood-analysis; Blood-stream; Quantitative-analysis; Dose-response; Sensitization; Author Keywords: Contact sensitizer; Local lymph node assay; Spleen; Peripheral lymph nodes
Contact
Itai Chipinda, Health Effects Laboratory Division, Allergy and Clinical Immunology Branch, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
TXCYAC
Publication Date
20090316
Document Type
Journal Article; Academic/Scholarly
Email Address
IChipinda@cdc.gov
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0300-483X
NIOSH Division
HELD
Priority Area
Services
Source Name
Toxicology
State
WV
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