CCR3 blockade as a new therapy for asthma

Abstract

Among the inflammatory cells infiltrating the lungs of asthmatic patients, eosinophils and Th2 cells are thought to play a central role in the pathogenesis of this disease. Several studies have implicated that chemokines are prime candidates for being responsible for the selective recruitment of the leukocyte subsets found in atopic diseases. Regulated upon activation, normal T-cell-expressed and secreted (RANTES), monocyte chemoattractant protein-3 (MCP-3), MCP-4 and the eotaxins, for example, have been shown in vitro to potently induce eosinophil chemotaxis as well as initiate several other pro-inflammatory activities such as integrin activation, lipid mediator biosynthesis and degranulation. Ligand binding and chemotaxis experiments with these chemokines demonstrated that a G-protein coupled-receptor (GPCR) cloned from eosinophils, termed CCR3, was responsible for producing a chemokine selectivity profile identical to that of eosinophils. In addition, blocking CCR3 on eosinophils, with a monoclonal ant...