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Respiratory toxicology and immunotoxicology in precision cut lung slices (PCLS)

: Sewald, K.; Switalla, S.; Henjakovic, M.; Krug, N.; Braun, A.


Abstracts of the 45th Congress of the European Societies of Toxicology : Rhodes, Greece, 5 - 8 October 2008
Amsterdam: Elsevier, 2008 (Toxicology letters 180.2008, Supplement 1)
ISSN: 0378-4274
European Societies of Toxicology (Eurotox Congress) <45, 2008, Rhodes>
Conference Paper, Journal Article
Fraunhofer ITEM ()
precision cut lung slice; respiratory toxicology; immunotoxicology

A variety of chemicals are known to cause sensitization of the respiratory tract. PCLS offer the opportunity to gain insight into lung morphology and physiology after in vitro exposure to chemicals. Aim of this study was the evaluation of PCLS as an ex vivo model to test for chemical-induced irritation and inflammation in lung tissue.
PCLS were prepared and exposed to LPS, respiratory and contact allergens. Vitality of PCLS was controlled by measurement of LDH and live/dead staining for confocal microscopy. Cytokines were detected with Luminex and ELISA.
The immune stimulating activity of LPS induced profound pro-inflammatory effects on cytokines such as IL-1( and TNF(. A strong surface expression of MHC class II, but not CD40, CD11c and CD86 could be observed. This result shows that PCLS per se provide a suitable in vitro model to predict immune modulating potencies of substances.
Chemical-induced local respiratory irritation and inflammation were characterized in PCLS. EC50 values were determined, correlated to in vivo exposure levels and induced cytokines were quantified. There is a clear evidence that chemical-induced loss of cell viability is accompanied by the production of pro-inflammatory cytokines. But, for some allergens we found an induction of cytokines at subtoxic concentrations. For example, non-toxic concentrations of respiratory allergen AHCP increased TNF( and IL-1( while the contact allergen cinnamaldehyde was not able to induce the expression of the same cytokines in lung tissue. It still needs to be elucidated to which extent a concurrent irritation influences the inflammation processes induced by allergens.