PMID- 18775882
OWN - NLM
STAT- MEDLINE
DCOM- 20090122
LR  - 20201209
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 106
IP  - 2
DP  - 2008 Dec
TI  - Ex vivo lung function measurements in precision-cut lung slices (PCLS) from 
      chemical allergen-sensitized mice represent a suitable alternative to in vivo 
      studies.
PG  - 444-53
LID - 10.1093/toxsci/kfn178 [doi]
AB  - A wide range of industrial chemicals can induce respiratory allergic reactions. 
      Hence, there is an urgent need for methods identifying and characterizing the 
      biological action of chemicals in the lung. Here, we present an easy, reliable 
      alternative method to measure lung function changes ex vivo after exposure to 
      chemical allergens and compare this to invasive in vivo measurements after 
      sensitization with the industrial chemicals trimellitic anhydride (TMA) and 
      2,4-dinitrochlorobenzene (DNCB). Female BALB/c mice were sensitized 
      epicutaneously with the respiratory allergen TMA and the contact sensitizer DNCB. 
      The early allergic response to TMA and DNCB was registered in vivo and ex vivo on 
      day 21 after inhalational challenge with dry standardized aerosols or after 
      exposure of precision-cut lung slices (PCLS) to dissolved allergen. Airway 
      hyperresponsiveness (AHR) to increasing doses of methacholine (MCh) was measured 
      on the next day in vivo and ex vivo. Bronchoalveolar lavage (BAL) was performed 
      for immunological characterization of local inflammation. TMA-sensitized mice 
      showed AHR to MCh in vivo (ED(50): 0.06 microg MCh vs. 0.21 microg MCh in 
      controls) and in PCLS (EC(50): 0.24 microM MCh vs. 0.4 microM MCh). TMA-treated 
      animals showed increased numbers of eosinophils (12.8 x 10(4) vs. 0.7 x 10(4)) 
      and elevated eotaxin-2 concentrations (994 pg/ml vs. 167 pg/ml) in BAL fluid 24 h 
      after allergen challenge. In contrast, none of these parameters differed after 
      sensitization with DNCB. The present study suggests that the effects of low 
      molecular weight allergens, like TMA and DNCB, on ex vivo lung functions tested 
      in PCLS reflect the in vivo situation.
FAU - Henjakovic, M
AU  - Henjakovic M
AD  - Department of Immunology, Allergology and Immunotoxicology, Fraunhofer Institute 
      of Toxicology and Experimental Medicine, 30625 Hannover, Germany.
FAU - Martin, C
AU  - Martin C
FAU - Hoymann, H G
AU  - Hoymann HG
FAU - Sewald, K
AU  - Sewald K
FAU - Ressmeyer, A R
AU  - Ressmeyer AR
FAU - Dassow, C
AU  - Dassow C
FAU - Pohlmann, G
AU  - Pohlmann G
FAU - Krug, N
AU  - Krug N
FAU - Uhlig, S
AU  - Uhlig S
FAU - Braun, A
AU  - Braun A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080904
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Allergens)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Phthalic Anhydrides)
RN  - 0W5ETF9M2K (Methacholine Chloride)
RN  - 80T61EUU7H (trimellitic anhydride)
SB  - IM
MH  - Allergens/*toxicity
MH  - Animals
MH  - Bronchial Hyperreactivity
MH  - Bronchoalveolar Lavage Fluid
MH  - Bronchoconstriction/drug effects
MH  - Dinitrochlorobenzene/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - In Vitro Techniques
MH  - Lung/*drug effects/physiology
MH  - Methacholine Chloride/*toxicity
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phthalic Anhydrides/*toxicity
MH  - Pneumonia/chemically induced
MH  - Respiratory Function Tests
EDAT- 2008/09/09 09:00
MHDA- 2009/01/23 09:00
CRDT- 2008/09/09 09:00
PHST- 2008/09/09 09:00 [pubmed]
PHST- 2009/01/23 09:00 [medline]
PHST- 2008/09/09 09:00 [entrez]
AID - kfn178 [pii]
AID - 10.1093/toxsci/kfn178 [doi]
PST - ppublish
SO  - Toxicol Sci. 2008 Dec;106(2):444-53. doi: 10.1093/toxsci/kfn178. Epub 2008 Sep 4.