Introduction
The nasal epithelium represents the point of first contact between the
respiratory system and the external environment. The nasal epithelium is
comprised of goblet, basal and ciliated cells, which are essential in
establishing mucociliary clearance, producing anti-microbial peptides,
chemokines and cytokines, and forming a protective barrier. The normal
respiratory epithelium has the ability to remodel and repair its
integrity after epithelial damage 1,2. Persistent
asthma is associated with epithelial dysfunction, associated with a
disturbance of the normal ability to repair wounds 3.
Studies using primary bronchial epithelial cells, obtained from children
with atopy and/or “asthma” and grown in submerged, monolayer cultures,
suggest an inability to heal wounds (reviewed in 4).
While these results are consistent with observations from bronchial
biopsies in adults with persistent asthma 3,
submerged, monolayer cultures do not adequately represent the conditions
seen in a fully differentiated pseudostratified epithelium in
vivo 5. To minimize these deficiencies primary
airway epithelial cells can be grown at the air-liquid interface (ALI)
into a fully differentiated pseudostratified epithelium consisting of
basal, goblet and ciliated cells 6.
Respiratory viral infections are involved in the induction and
progression of asthma 7,8. Wheezing and asthma
exacerbation, especially in children and the elderly, are often
associated with respiratory infections due to respiratory viruses such
as respiratory syncytial virus (RSV) and human rhinovirus infection9,10. Debate exists about whether the asthmatic
respiratory epithelium has an exaggerated response to respiratory viral
infections but evidence from in vivo and ex vivo studies
show a different pattern of cytokine secretion from “asthmatic”
epithelial cells under baseline and stimulated conditions1,11. Certainly, the inflammatory milieu differs in
the “asthmatic” airway when compared to that in healthy individuals3. How this milieu influences wound healing is little
studied.
We have recently developed an ex vivo model for assessing wound
healing in a well-differentiated epithelium, grown at the air-liquid
interface (ALI), using primary nasal epithelial cells (NECs)6. The aim of the present study was to use our model
to determine: a) the ability of a nasal epithelium, grown in ALI
culture, from cells obtained from subjects with asthma and/or atopy, to
heal a wound, and b) to determine the influence of the “asthmatic”
airway milieu on wound healing. We chose to use primary NECs obtained
from adults to avoid the uncertainties in asthma diagnosis in children.
Methods ( full details can be found in the online supplement)