PMID- 24412833
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20140331
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 28
IP  - 4
DP  - 2014 Jun
TI  - Assessment of immunotoxicity induced by chemicals in human precision-cut lung 
      slices (PCLS).
PG  - 588-99
LID - S0887-2333(13)00341-X [pii]
LID - 10.1016/j.tiv.2013.12.016 [doi]
AB  - Occupational asthma can be induced by a number of chemicals at the workplace. 
      Risk assessment of potential sensitizers is mostly performed in animal 
      experiments. With increasing public demand for alternative methods, human 
      precision-cut lung slices (PCLS) have been developed as an ex vivo model. Human 
      PCLS were exposed to increasing concentrations of 20 industrial chemicals 
      including 4 respiratory allergens, 11 contact allergens, and 5 non-sensitizing 
      irritants. Local respiratory irritation was characterized and expressed as 75% 
      (EC25) and 50% (EC50) cell viability with respect to controls. Dose-response 
      curves of all chemicals except for phenol were generated. Local respiratory 
      inflammation was quantified by measuring the production of cytokines and 
      chemokines. TNF-alpha and IL-1alpha were increased significantly in human PCLS after 
      exposure to the respiratory sensitizers trimellitic anhydride (TMA) and ammonium 
      hexachloroplatinate (HClPt) at subtoxic concentrations, while contact sensitizers 
      and non-sensitizing irritants failed to induce the release of these cytokines to 
      the same extent. Interestingly, significant increases in T(H)1/T(H)2 cytokines 
      could be detected only after exposure to HClPt at a subtoxic concentration. In 
      conclusion, allergen-induced cytokines were observed but not considered as 
      biomarkers for the differentiation between respiratory and contact sensitizers. 
      Our preliminary results show an ex vivo model which might be used for prediction 
      of chemical-induced toxicity, but is due to its complex three-dimensional 
      structure not applicable for a simple screening of functional and behavior 
      changes of certain cell populations such as dendritic cells and T-cells in 
      response to allergens.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Lauenstein, L
AU  - Lauenstein L
AD  - Department of Airway Immunology, Fraunhofer Institute for Toxicology and 
      Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung 
      Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, 
      Germany.
FAU - Switalla, S
AU  - Switalla S
AD  - Department of Airway Immunology, Fraunhofer Institute for Toxicology and 
      Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung 
      Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, 
      Germany.
FAU - Prenzler, F
AU  - Prenzler F
AD  - Department of Airway Immunology, Fraunhofer Institute for Toxicology and 
      Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung 
      Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, 
      Germany.
FAU - Seehase, S
AU  - Seehase S
AD  - Department of Airway Immunology, Fraunhofer Institute for Toxicology and 
      Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung 
      Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, 
      Germany.
FAU - Pfennig, O
AU  - Pfennig O
AD  - KRH-Klinikum Nordstadt, Hanover, Germany.
FAU - Forster, C
AU  - Forster C
AD  - KRH-Klinikum Nordstadt, Hanover, Germany.
FAU - Fieguth, H
AU  - Fieguth H
AD  - KRH-Klinikum Nordstadt, Hanover, Germany.
FAU - Braun, A
AU  - Braun A
AD  - Department of Airway Immunology, Fraunhofer Institute for Toxicology and 
      Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung 
      Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, 
      Germany.
FAU - Sewald, K
AU  - Sewald K
AD  - Department of Airway Immunology, Fraunhofer Institute for Toxicology and 
      Experimental Medicine, Biomedical Research in Endstage and Obstructive Lung 
      Disease Hanover (BREATH), Member of the German Center for Lung Research, Hanover, 
      Germany. Electronic address: katherina.sewald@item.fraunhofer.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140110
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Allergens)
RN  - 0 (Cytokines)
RN  - 0 (Irritants)
SB  - IM
MH  - Aged
MH  - Allergens/*immunology/toxicity
MH  - Cell Survival/drug effects
MH  - Cytokines/metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Irritants/*toxicity
MH  - Lung/*drug effects
MH  - Male
MH  - Middle Aged
MH  - Tissue Culture Techniques
OTO - NOTNLM
OT  - Asthma
OT  - Contact sensitizer
OT  - Low-molecular-weight chemicals
OT  - Pro-inflammatory cytokines
OT  - Respiratory allergy
OT  - Respiratory sensitizer
EDAT- 2014/01/15 06:00
MHDA- 2015/06/30 06:00
CRDT- 2014/01/14 06:00
PHST- 2013/06/11 00:00 [received]
PHST- 2013/12/17 00:00 [revised]
PHST- 2013/12/23 00:00 [accepted]
PHST- 2014/01/14 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
AID - S0887-2333(13)00341-X [pii]
AID - 10.1016/j.tiv.2013.12.016 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2014 Jun;28(4):588-99. doi: 10.1016/j.tiv.2013.12.016. Epub 
      2014 Jan 10.