The beta chemokine receptor CCR3 is highly expressed on eosinophils, basophils and to a lesser extent on TH2 lymphocytes. Noteworthy, these cell types are all critical for the development of an inflammatory allergic response. Concomittantly, the expression of the ligands for this receptor, eotaxin, eotaxin-2, MCP-3, 4 and RANTES, have all been associated with disease states where eosinophils are prevalent, e.g. allergic asthma, helminthic parasitic infection and ulcerative colitis. To investigate that eosinophils are required for eosinophil trafficking in normal and inflammatory disease states, we have generated mice deficient in this receptor. We hypothesize that activated eosinophil trafficking to sensitized lungs is largely CCR3 dependent but believe that other mediators also play a role, we anticipate that the complement receptor C3aR is one such mediator. Preliminary data provide an unexpected role for CCR3 in regulating intinsic airway tone, study of the mechanisms of this receptor's role in airway hyperreponsiveness may provide insight into disease initiation and opportunity for development and evaluation of therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL010463-01
Application #
6212293
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (02))
Project Start
2000-08-03
Project End
Budget Start
2000-08-03
Budget End
2001-08-02
Support Year
1
Fiscal Year
2000
Total Cost
$37,516
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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