Allergen-induced injury to the epithelial mesenchymal trophic unit in mild atopic asthmatics

Abstract

Rationale We previously reported that intradermal allergen challenge induces myofibroblast formation, tenascin deposition together with other markers of repair in atopic allergic subjects. In this study we have determined whether inhalational allergen challenge in mild asthmatics induces similar changes in the epithelial mesenchymal trophic unit (EMTU). Methods Endobronchial mucosal biopsies were taken from 8 mild atopic asthmatics before and 24 hours after inhalational allergen challenge. Extracellular matrix (ECM) deposition in the reticular basement membrane (RBM) was measured by confocal microscopy. Cells actively involved in ECM synthesis were identified as immunoreactive to Hsp47, a chaperone of collagen synthesis. IL-4/13 and TGF–β activated cells of the EMTU were identified by specific Ab to phosphorylated (p)STAT6 and pSMAD2 respectively. Results After allergen challenge there was a significant increase in the thickness of tenascin in the RBM (p=0.031), and the numbers of Hsp47 positive fibroblasts (p=0.003) within the EMTU. There was an increase in the numbers of inflammatory cells and elevated expression of TGF–β1 and IL-13, with significant increases in the number of pStat6+ (p=0.037) and pSmad2+ (p=0.042) epithelial cells, and nuclear pSmad2+ fibroblasts (p=0.031), post-allergen challenge. Conclusions Allergen challenge in mild asthmatics induces activation of epithelial cells and fibroblasts in the EMTU as well as increased tenascin deposition within the RBM.