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Species comparison of interleukin-13 induced airway hyperreactivity in precision-cut lung slices

 
: Danov, Olga; Jiménez Delgado, Sharon Melissa; Drake, Helena; Schindler, Susann; Pfennig, Olaf; Förster, Christine; Braun, Armin; Sewald, Katherina

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Pneumologie 68 (2014), No.6, pp.407
ISSN: 0934-8387
International Symposium "Lung Regeneration and Beyond - BREATH meets REBIRTH" <3, 2014, Hannover>
English
Journal Article, Conference Paper
Fraunhofer ITEM ()

Abstract
Interleukin-13 is a key cytokine of asthma and elevated in asthmatics resulting in airway hyperresponsiveness (AHR). AHR is a hallmark of allergic asthma defined as exaggerated bronchoconstriction in response to contractile stimuli. Research for the development of new drugs is mainly based on appropriate in vivo and in vitro models. There is a need for translational models with improved predictivity for human. For comparison of different species we used precision-cut lung slices (PCLS) and assessed IL-13 induced hyperreactivity in PCLS of mice, rats, and humans.
PCLS were prepared from Balb/c mice, Brown Norway rats, and humans. IL-13 receptor was stained in the airways of mouse, rat and human PCLS by immunohistochemistry. Airways of all species were pre-incubated with 100 ng/mL IL-13. Subsequently, bronchoconstriction was induced by addition of methacholine (MCh) and visualized by videomicroscopy.
IL-13 receptor was present in epithelial cells and smooth muscle cells in PCLS of all species. Methacholine-induced bronchoconstriction in mouse exhibited an EC50 of 80 nM and decreased by pre-incubation with IL-13 to 50 nM, in rat from 220 nM to 170 nM and human from 180 nM to 47 nM MCh. In general, pre-incubation of PCLS in the presence of IL-13 resulted in all species in stronger bronchoconstriction at maximum methacholine concentration. Maximal constriction of initial airway area resulted in mouse in Cmax 61% by control and decreased in IL-13 pre-incubated tissue to 80%, in rat by 49% to 69% and human by 85% to 94% compared to untreated tissue.
This study shows that IL-13 receptor is similar distributed in epithelial cells and smooth muscle cells of all three species. IL-13 induced airway hyperreactivity in all tested species with different methacholine sensitivity. In future studies, PCLS will be used for pre-clinical studies to valuate the antagonist efficacy.

: http://publica.fraunhofer.de/documents/N-333070.html