Abstract
Studies in animals and in human atopic skin suggest that allergen
challenge may activate acute tissue remodeling changes via transforming
growth factor-beta pathways. We determined whether inhalational allergen
challenge in subjects with mild asthma induces similar acute changes to
the airway epithelial mesenchymal trophic unit (EMTU). Endobronchial
mucosal biopsies obtained before and 24 h after challenge were examined
by confocal microscopy for extracellular matrix deposition in the
reticular basement membrane (RBM). Cells actively involved in
extracellular matrix synthesis were identified as immunoreactive to heat
shock protein 47, a chaperone of Collagen synthesis. Interleukin-4/13
and transforming growth factor-beta-activated cells were identified by
specific antibodies to phosphorylated (phospho-) signal transducer and
activator of transcription 6 and phospho-Smad2, respectively. After
allergen challenge, there was a significant increase in the number of
heat shock protein 47-positive airway fibroblasts (P = 0.003) and in the
thickness of tenascin in the RBM (P = 0.031). There were also increases
in the number of phospho-Smad2+ epithelial cells (P = 0.04) and nuclear
phospho-Smad2+ fibroblasts (P = 0.03), as well as phospho-signal
transducer and activator of transcription 6+ epithelial cells (P =
0.03), after allergen challenge. Thus, allergen challenge in patients
with mild asthma induces activation of epithelial cells and fibroblasts
in the EMTU as well as increased tenascin deposition within the RBM.
Airway remodeling in asthma may, in part, result from repeated acute
activation of the EMTU by allergen exposure.
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