PMID- 16876979
OWN - NLM
STAT- MEDLINE
DCOM- 20061226
LR  - 20090410
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 20
IP  - 8
DP  - 2006 Dec
TI  - Respiratory immunotoxicity: an in vitro assessment.
PG  - 1249-64
AB  - As yet, in vitro assessment of the immunotoxic potency of respiratory agents is 
      not possible. The complexity of the endpoint and the respiratory tract, and the 
      limited availability of well-documented respiratory agents are the main reasons. 
      The evidence that epithelial cells (ECs) are triggered by compounds to express in 
      vitro surface proteins and soluble mediators, has stimulated their use for 
      developing tests for respiratory immunotoxicity. A variety of airway ECs and 
      EC-lines have been assessed, but the available information seems to point at 
      human alveolar cells (e.g., A549) as the most convenient cell type. EC-based test 
      formats with various degrees of complexity have been assessed. Sofar, promising 
      results were obtained using a 3D model using the human A549 lung cell line. 
      Dendritic cells (DCs) have been subjected to intensive research. However, 
      currently available tests are not well suited to discern among the potency of 
      sensitizers. Potential explanations include the lack of standardised protocols 
      for the generation of DCs, no good standards for estimating the quality of in 
      vitro derived DC-cultures, and limited dynamics of the currently used end-points. 
      Alveolar macrophages (AMs) have so far received less attention. This may proof 
      unjustified as macrophages may link innate responses to adaptive immunity. The 
      observation that ECs, DCs and AMs affect each other, suggests that test formats 
      are required combining at least two of these cell types if ranking of compounds 
      according to their sensitising potency is the aim. In addition, the capacity of 
      compounds to cross a cellular membrane is an important property of an immunotoxic 
      compound, which can be assessed only in 3D reconstituted human tissue models. 
      While promising data have been reported for the skin, immunocompetent 3D 
      reconstituted human lung remains to be evaluated for respiratory immunotoxicity. 
      Obviously, the success of any of these simplified test (as compared to the 
      complexity of the immune response) is highly dependent on the availability of 
      early stage biomarkers (expressed at mucosal barrier level) that are predictive 
      for relevant immunotoxicity mechanisms occurring down-stream of the immune 
      response. As yet, such biomarkers are not yet available.
FAU - Roggen, Erwin L
AU  - Roggen EL
AD  - Department of Protein Screening, Molecular Biotechnology, Novozymes AS 
      Smoermosevej 11, 2880 Bagsvaerd, Denmark. elro@novozymes.com
FAU - Soni, Nanna Kristensen
AU  - Soni NK
FAU - Verheyen, Geert R
AU  - Verheyen GR
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20060425
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
SB  - IM
MH  - Animals
MH  - Dendritic Cells/immunology/pathology
MH  - Epithelial Cells/immunology/pathology
MH  - Humans
MH  - Immune System Diseases/*etiology/pathology
MH  - Immunocompetence/physiology
MH  - Respiratory Tract Diseases/*complications/pathology
RF  - 117
EDAT- 2006/08/01 09:00
MHDA- 2006/12/27 09:00
CRDT- 2006/08/01 09:00
PHST- 2005/11/23 00:00 [received]
PHST- 2006/03/30 00:00 [revised]
PHST- 2006/03/31 00:00 [accepted]
PHST- 2006/08/01 09:00 [pubmed]
PHST- 2006/12/27 09:00 [medline]
PHST- 2006/08/01 09:00 [entrez]
AID - S0887-2333(06)00074-9 [pii]
AID - 10.1016/j.tiv.2006.03.009 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2006 Dec;20(8):1249-64. doi: 10.1016/j.tiv.2006.03.009. Epub 
      2006 Apr 25.