Project: Research project

Project Details


It has been previously shown that short-term and long-term exposures to
gaseous pollutants alter mucosal function in the airways. The mechanisms
underlying the associated depression in mucociliary clearance have been
partially elucidated. In particular, it has been shown that changes in
mucosal secretion rather than primary ciliary dysfunction are responsible
for this defect. However, it is not known if the observed functional
changes are caused by a direct effect of the pollutant on the mucociliary
apparatus or indirectly by the concomitant airway inflammation in analog to
the previously shown role of airway inflammation in pollutant induced
airway hyperreactivity. The purpose of this proposal is therefore to
determine in sheep if 1) the impairment of mucosal function by short-term
low-level O3 exposure (0.5-1 ppm for 2 hours) is associated with leukocytes
influx into the airway, 2) the prevention of leukocyte migration also
prevents pollutant induced mucosal dysfunction, 3) mucosal dysfunction is
related to inflammatory mediators, 4) the newborn airway is more vulnerable
to pollutant induced mucosal dysfunction than the adult airway, and 5)
pollutant induced mucosal dysfunction alters bacterial clearance in central
airways and if the bacterial clearance is modified by the inflammatory
response. The studies will be carried out in lambs and adult sheep and
focus on the trachea. Mucosal function will be assessed in vivo by the
determination of mucociliary transport with a radiographic technique and
airway wall water content using a double gas bolus method to detect mucosal
edema formation. Airway inflammation will be assessed by tracheal lavage
and biopsy, and the role of chemical mediators by mediator assay in lavage
fluid, and the use of appropriate antagonists. A bacterial aerosol will be
used to determine the persistence of viable bacteria in the trachea. To
suppress the inflammatory response, pluronic F-68, a potent inhibitor of
leukocyte migration will be used. We expect these studies to delineate the
role of inflammation in the impairment of mucosal function by O3. The
results might form the basis for pharmacologic modification of pollutant
induced mucociliary dysfunction.
Effective start/end date9/1/826/30/91


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Environmental Science(all)
  • Medicine(all)


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