PMID- 20060446
OWN - NLM
STAT- MEDLINE
DCOM- 20100408
LR  - 20100222
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 193
IP  - 2
DP  - 2010 Mar 15
TI  - A draining lymph node assay (DLNA) for assessing the sensitizing potential of 
      proteins.
PG  - 144-51
LID - 10.1016/j.toxlet.2009.12.020 [doi]
AB  - There is a need for a simple and predictive model to identify the respiratory 
      sensitization potential of (novel) proteins. The present study examined the use 
      of a mouse draining lymph node assay (DLNA) approach, employing several routes of 
      exposure, as a possible starting point for assessing protein sensitization 
      potential. Consistent with the experimental procedure for the standard local 
      lymph node assay (LLNA), female BALB/c mice were dosed dermally (topical), 
      intranasally (IN) or by oropharyngeal aspiration (OP) on days 1, 2 and 3, and 
      proliferation in the relevant draining lymph nodes was measured on day 6. For 
      each route, the auricular, superficial cervical and tracheobronchial lymph nodes 
      (TBLN) were evaluated following treatment with Subtilisin Carlsberg (SUB; a 
      potent sensitizer/allergen), ovalbumin (OVA; a potent food allergen), 
      beta-lactoglobulin (BLG; a moderate food allergen), and keyhole limpet hemocyanin 
      (KLH; a strong immunogen with no reports of respiratory sensitization). Initial 
      studies with OVA indicated that dermal administration did not stimulate lymph 
      node proliferation. Responses in the tracheobronchial lymph node were most 
      dramatic (stimulation indices up to 100) and reproducible for both the IN and OP 
      routes. In a comparative experiment, all proteins induced lymph node 
      proliferation with a rank order potency of SUB>KLH>OVA>BLG. The influence of the 
      endotoxin content on lymph node proliferation was determined to be minimal, and 
      did not impact the rank order potency. Molecular characterization of the TBLN at 
      an equipotent proliferative dose was conducted for select gene transcripts based 
      on research examining chemical sensitizers. Expression profiles differed among 
      the four proteins, but the relevance of these responses was not clear and they 
      did not further discriminate their allergic potential. These data illustrate both 
      the opportunities and challenges associated with the examination of the draining 
      lymph node proliferative response to assess the allergenic potential of proteins.
CI  - Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Boverhof, Darrell R
AU  - Boverhof DR
AD  - Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 
      Midland, MI 48674, USA. RBoverhof@dow.com
FAU - Gollapudi, B Bhaskar
AU  - Gollapudi BB
FAU - Hotchkiss, Jon A
AU  - Hotchkiss JA
FAU - Osterloh-Quiroz, Mandy
AU  - Osterloh-Quiroz M
FAU - Woolhiser, Michael R
AU  - Woolhiser MR
LA  - eng
PT  - Journal Article
DEP - 20100107
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Allergens)
RN  - 0 (Endotoxins)
RN  - 0 (Proteins)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Administration, Intranasal
MH  - Allergens/administration & dosage/*immunology
MH  - Animals
MH  - Biological Assay/*methods
MH  - Endotoxins/toxicity
MH  - Female
MH  - Gene Expression/drug effects
MH  - Lymph Nodes/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Models, Animal
MH  - Oropharynx/metabolism
MH  - Ovalbumin/adverse effects
MH  - Proteins/administration & dosage/*immunology
MH  - Respiratory Hypersensitivity/*immunology
EDAT- 2010/01/12 06:00
MHDA- 2010/04/09 06:00
CRDT- 2010/01/12 06:00
PHST- 2009/10/13 00:00 [received]
PHST- 2009/12/29 00:00 [revised]
PHST- 2009/12/30 00:00 [accepted]
PHST- 2010/01/12 06:00 [entrez]
PHST- 2010/01/12 06:00 [pubmed]
PHST- 2010/04/09 06:00 [medline]
AID - S0378-4274(10)00003-2 [pii]
AID - 10.1016/j.toxlet.2009.12.020 [doi]
PST - ppublish
SO  - Toxicol Lett. 2010 Mar 15;193(2):144-51. doi: 10.1016/j.toxlet.2009.12.020. Epub 
      2010 Jan 7.