VIRUS-INDUCED CHANGES IN AIRWAY EPITHELIAL FUNCTION

Project: Research project

Project Details

Description

This project deals with the effect of viral infection on the function of
the airway epithelial cell, the primary target of most respiratory
viruses. Alterations in both epithelial-smooth interactions and
epithelial ion transport will be studied. I have demonstrated that decreased epithelial neutral endopeptidase is
responsible for the increased airway smooth muscle response to substance
P seen with viral infections. In this project I will examine the effect
of viral infections on the response to other peptide mediators, both
excitatory and inhibitory and the role of decreased neutral
endopeptidase in these responses. Furthermore, I will examine the role
of endogenous tachykinins (whose activities are increased in the absence
of neutral endopeptidase) in causing the increased parasympathetic
bronchoconstriction characteristic if viral airway infection. I will
also determine the effect of viral infection on the release of
epithelial mediators that increase or decrease smooth muscle
contraction. In studying epithelial ion transport, which regulates water secretion, I
will first determine the effect of viral infection on baseline
(unstimulated) sodium absorption and chloride secretion, and the
dependence of such changes on epithelial prostaglandin production. I
will also examine the effect of viral infection on paracellular (between
cells) and transcellular (through) ion permeability. Finally, I will
determine the effect of decreased epithelial neutral endopeptidase on
the ion transport response to tachykinins and other peptide mediators. These studies should lead to a greater understanding of the role of
viral infections in airway hypersecretion and smooth muscle
hyperresponsiveness, as well as insights into the pathophysiologic
mechanisms of asthma. This may ultimately provide the basis for new
therapeutic strategies.
StatusFinished
Effective start/end date1/1/9112/31/95

Funding

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

ASJC

  • Medicine(all)

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