TAP--A NOVEL ANTIMICROBIAL PEPTIDE FROM THE TRACHEA

Project: Research project

Description

Pulmonary infections are responsible for significant morbidity and
mortality, particularly in hosts with compromised defenses. One of the
many important physiological roles of the epithelial cells of the
respiratory mucosa is to provide defense of the mammalian airway from
potential pathogenic agents present in inspired air. A more complete
definition of the defense mechanisms of these cells will contribute to our
understanding of the pathophysiology of airway disease, ultimately leading
to more rational therapeutic interventions. The isolation and characterization of antimicrobial peptides, such as
cecropins, magainins and defensins, in a variety of species and tissues has
unveiled a previously unrecognized component of host defense. Recently, a
novel, cysteine-rich antimicrobial peptide has been isolated and
characterized from bovine tracheal mucosa, and its cDNA has been cloned.
This peptide, named Trachea] Antimicrobial Peptide (TAP), is present in
high abundance in the tracheal mucosa and has potent broad-spectrum
antimicrobial activity in vitro. Preliminary data suggest that cells of
the respiratory epithelium make this molecule. The goal of this project is
to extend our understanding of biochemistry of this novel peptide. Several hypotheses are proposed: First, TAP expression is developmentally
regulated and is made by epithelial cells of the trachea (and possibly by
similar cells in other anatomical locations). Second, TAP is stored in
airway epithelial cells. Third, a homologous peptide is made by human
tracheal mucosal cells. Fourth, the structure and function of TAP is
critically dependent on a defined cysteine pairing. To address these hypotheses the following experiments will be performed: 1.
Tissue and developmental expression of TAP will be determined by messenger
RNA analysis, including in situ hybridization; 2. Cellular and subcellular
localization will be determined by immunohistochemistry; 3. The cDNA for
human TAP will be cloned; 4. The disulfide-array for TAP will be
determined. TAP is likely to contribute to the antimicrobial defense of the respiratory
epithelium of mammals. The understanding of its biological role may lead
to the eventual therapeutic modulation of endogenous antimicrobial peptide
expression and may facilitate the development of therapeutic antimicrobials
designed to work in the respiratory tract.
StatusFinished
Effective start/end date2/1/929/29/98

Funding

  • National Institutes of Health: $220,620.00
  • National Institutes of Health
  • National Institutes of Health: $214,531.00
  • National Institutes of Health

Fingerprint

Trachea
Peptides
Epithelial Cells
Mucous Membrane
trypsinogen activation peptide
Respiratory Mucosa
Cysteine
Magainins
Complementary DNA
Defensins
Mammals
Disulfides
Respiratory System
Biochemistry
In Situ Hybridization
Therapeutics
Immunohistochemistry
Air
Morbidity
Lung

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)