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CCR3 blockade as a new therapy for asthma
1Inflammatory Diseases Unit, Roche Bioscience, Palo Alto, CA 94304, USA. claude.bertrand@wl.com
Expert Opinion on Investigational Drugs
|November 4, 2000
Summary
Chemokine receptor CCR3 is crucial for eosinophil and T-cell recruitment in asthma. Blocking CCR3 effectively halts eosinophil responses, offering a promising new therapeutic strategy for asthma treatment.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- Eosinophils and Th2 cells are key players in asthma pathogenesis.
- Chemokines are implicated in selective leukocyte recruitment in atopic diseases.
- Specific chemokines like RANTES, MCP-3, MCP-4, and eotaxins induce eosinophil chemotaxis and pro-inflammatory activities.
Purpose of the Study:
- To investigate the role of chemokine receptor CCR3 in eosinophil and T-cell trafficking in asthma.
- To determine if CCR3 is responsible for the chemokine selectivity profile observed in eosinophils.
- To evaluate CCR3 blockade as a potential therapeutic strategy for asthma.
Main Methods:
- In vitro ligand binding and chemotaxis assays using chemokines and eosinophils.
- Cloning of the G-protein coupled-receptor (GPCR) CCR3 from eosinophils.
- Experiments involving monoclonal antibody blockade of CCR3 on eosinophils.
- Analysis of CCR3 expression on Th2 cells and T-cells in diseased tissue.
Main Results:
- CCR3 demonstrated a chemokine selectivity profile identical to that of eosinophils.
- Blocking CCR3 on eosinophils with a monoclonal antibody completely inhibited their responses to tested chemokines.
- CCR3 was detected on in vitro derived Th2 cells and T-cells co-localizing with eosinophils in asthmatic tissue.
Conclusions:
- CCR3 plays a central role in eosinophil trafficking.
- CCR3 mediates the recruitment of Th2 cells into the airways, contributing to asthma pathogenesis.
- CCR3 blockade represents a highly attractive and innovative therapeutic strategy for asthma.