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 airway epithelium (line NJ.1726). Specifically, this proposal will correlate induced pulmonary pathologies (including measurements of airway hyper- responsiveness) 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 """"""""sensitize"""""""" individuals to exacerbating effects of exposure to aerosolized antigen (i.e., allergic inflammation). Moreover, the proposal outlines specific experiments to identify leukocyte- specific activities in the lung and to evaluate the synergistic effect of IL-5 expression on the other inflammatory signaling cascades. An important intent of this proposal is to integrate these genetic approaches in the mouse with the downstream pulmonary consequences accompanying allergic respiratory inflammation. The specific objectives of this proposal are: (1) To determine the lymphocyte dependence (i.e., the specific subpopulations of T and B cells) of the pulmonary pathologies occurring in transgenic mice constitutively expressing IL-5 in the lung (line NJ.1726); (2) To assess the contribution of IL-5 as an inflammatory signal in type I-hypersensitivity reactions occurring in the lung (i.e., allergic pulmonary inflammation); (3) 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL010176-02
Application #
6183019
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
2000-09-30
Project End
Budget Start
2000-09-30
Budget End
2001-09-29
Support Year
2
Fiscal Year
2000
Total Cost
$42,628
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905