MOUSE MODELS OF EOSINOPHIL ASSOCIATED LUNG DYSFUNCTION

Project: Research project

Project Details

Description

DESCRIPTION: This proposal seeks to define IL-5 effector functions in the
lung leading to pulmonary pathology and lung dysfunction. The focus of the
proposal is to identify IL-5-dependent cell and molecular pulmonary changes
using a transgenic mouse model of asthma constitutively expressing IL-5 from
the airwa epithelium (line NJ.1726). Specifically, this proposal will
correlate induced pulmonary pathologies (including measurements of airway
hyperresponsiveness) occurring in NJ.1726 mice with the recruitment of
eosinophils and specific lymphocyte subpopulations. We will also determine
if pulmonary changes induced by IL-5 expression in the lung "sensitizes"
individuals to exacerbating effect of exposure to aerosolized antigen (i.e.,
allergic inflammation) or environmental pollutants such as ozone. Moreover,
the proposal outlines specific experiments to identify eosinophil-associated
activities in the lung and to evaluate the synergistic effects of IL-5
expression on other inflammatory signaling cascades. An important intent of
this proposal is to integrate our approaches to understand eosinophil
effector function in the mouse with the downstream pulmonary consequences of
the recruitment and activation of this cell type in the lung. The specific
objectives of this proposal are: 1) to determine the lymphocyte dependence
(i.e., the specific populations of T and B cells) of the pulmonary
pathologies occurring in transgenic mice constitutively expressing IL-5 in
the lung (line NJ.1736); 2) To test if IL-5 expression in the airway
epithelium/lumen of NJ.1726 mice induces pulmonary immune changes that
predispose individuals to exaggerated responses to exacerbating inflammatory
stimuli; 3) To determine if the IL-5-dependent recruitment in eosinophils to
the lung mucosa and airway lumen of mice is the causative event leading to
pulmonary pathology; 4) To test if synergistic effects between IL-5 and
chemokines expressed in the lung are responsible for lung pathologies
observed in mice and asthmatic patients exposed to allergens and/or
environmental pollutants.
StatusFinished
Effective start/end date4/1/9811/30/13

Funding

  • National Heart, Lung, and Blood Institute: $313,717.00
  • National Heart, Lung, and Blood Institute: $383,276.00
  • National Heart, Lung, and Blood Institute: $400,000.00
  • National Heart, Lung, and Blood Institute: $392,500.00
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute: $376,992.00
  • National Heart, Lung, and Blood Institute: $400,000.00
  • National Heart, Lung, and Blood Institute: $400,000.00
  • National Heart, Lung, and Blood Institute: $400,000.00
  • National Heart, Lung, and Blood Institute: $392,500.00
  • National Heart, Lung, and Blood Institute: $392,500.00
  • National Heart, Lung, and Blood Institute: $323,128.00

ASJC

  • Medicine(all)

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