RT Journal Article SR Electronic T1 Investigations on the role of region-specific IL-13 receptor alpha 1 expression along the airway tree in mucus production in asthma JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 4539 VO 40 IS Suppl 56 A1 Christina Vock A1 Ali Önder Yildirim A1 Christina Wagner A1 Heinz Fehrenbach A1 Michael Wegmann YR 2012 UL http://erj.ersjournals.com/content/40/Suppl_56/4539.abstract AB Increased mucus production is a critical factor impairing lung function in patients suffering from bronchial asthma. In acute and chronic mouse models of allergic asthma metaplasia of mucus producing goblet cells (GC) was found in proximal but not in distal airways although secretion of interleukin (IL)-13, the main trigger of mucus production, was significantly elevated along the entire airway tree. The current study aimed at elucidating what detains TH2 cell derived IL-13 from inducing mucus in distal airways.BALB/c mice were sensitized with OVA/Alum and subsequently challenged with OVA for one (acute) or twelve weeks (chronic). Lungs were fixed under constant pressure with 4% PFA followed by paraffin embedding. Samples were stained with PAS to analyse mucus production. Quantitative (q)PCR was performed on microdissected airways and airway epithelial cells isolated by laser-capture microdissection (LCM).QPCR revealed higher expression of IL-13Rα1 in proximal versus distal airways in both acutely (1.5-fold) and chronically (1.5-fold) challenged mice. Similarly, in PBS-treated control mice expression of IL-13Rα1 was higher in proximal airways (1.3-fold) and even more prominent in epithelial cells (2-fold) isolated by LCM from proximal airways.Expression levels of transcription factors down-stream the IL-13Rα1 signalling implicated in mucus hyper-production, such as Spdef or FoxA2, were also region-specifically regulated.These results suggest, that the low expression of IL-13Rα1 and hence, the reduced sensitivity towards IL-13, might protect distal airways from mucus plugging which would impair ventilation of the alveoli of the respective acinus.