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Precision cut lung slices (PCLS) for respiratory sensitisation potential testing of allergens and irritants

: Henjakovic, M.; Sewald, K.; Switalla, S.; Veres, T.; Mätz-Rensing, K.; Krug, N.; Braun, A.


44th Congress of the European Societies of Toxicology, EUROTOX 2007. Abstracts : Amsterdam, The Netherlands, 7 - 10 October 2007
Amsterdam: Elsevier, 2007 (Toxicology letters 172.2007, Supplement 1)
ISSN: 0378-4274
European Societies of Toxicology (Congress) <44, 2007, Amsterdam>
Conference Paper, Journal Article
Fraunhofer ITEM ()
precision cut lung slice; respiratory sensation; irritant; allergen

Technique of PCLS provides the possibility to address cellular and functional response to allergen substances under ex vivo conditions. Objective of this work is the assessment of the respiratory sensitizing potential of substances, e.g. TMA and DNCB in PCLS with focus on cytokine release pattern and dendritic cell markers MHCII and CD86.
Extracted mouse and primate lungs were filled with medium-agarose solution and cut with a microtome. After preparation of PCLS with a thickness of 220 ± 20 µm slices were cultivated for several days under cell culture conditions. Vitality of lung slices was controlled by LDH measurements in supernatant and calcein AM/EthD-1 staining for CLSM. Dose dependent cytokine release patterns were assayed by cytokine array Luminex or ELISA.
Mouse and primate PCLS were incubated with increasing concentrations of LPS and non-toxic doses of TMA and DNCB. TMA induced 80-100% increase in cytokine release of MCP-1, IL-1alpha, IL-8, GCSF and 50 % of MIP-1beta in primate PCLS. DNCB increased 60-100% cytokine production of MCP-1beta, GCSF and IL-1alpha in primate PCLS. Production of these cytokines was increased in mouse PCLS by TMA incubation to 20-60%, DNCB exposure showed no significant changes. Changes in the expression pattern of functional dendritic cell surface markers MHCII and CD86 have been observed in LPS stimulated PCLS in situ using CLSM.
We established a new ex vivo model to estimate the respiratory sensitising potential of allergens and irritants in non-sensitised mouse and primate lung slices with immunomodulants LPS, dexamethasone and model allergens TMA and DNCB.