BACKGROUND: During inflammation, neutrophils, basophils, and eosinophils release cell type-specific mediators and proteases through signaling molecules, such as G protein-coupled receptors and ion channels. As such, ion channels and receptors, including G protein-coupled receptors, are common drug targets. OBJECTIVE: We sought to identify, for the first time, ion channels and receptors preferentially expressed by each granulocyte subtype. METHODS: Using GeneChip, we compared approximately 20,000 transcripts present in 7 leukocyte types, platelets, mast cells, and fibroblasts to identify granulocyte subtype-selective transcripts for receptors and ion channels. Granulocyte subtype-selective transcripts were chosen on the basis of several conditions, such as the transcript having a 5-fold or greater expression level compared with the maximum level of other leukocytes. RESULTS: Fifty-one transcripts were chosen to be preferentially expressed by each granulocyte subtype. Seventeen of the 51 transcripts have not been previously reported as granulocyte subtype selective. Among the 17 receptors and ion channels, 6 were basophil selective, eosinophil selective, or both and were not highly expressed by other organs, indicating that they might be potential targets for antiallergy drugs. CONCLUSION: Use of this database of potential cell type-selective drug targets should minimize the efforts required for pharmaceutical development.
BACKGROUND: During inflammation, neutrophils, basophils, and eosinophils release cell type-specific mediators and proteases through signaling molecules, such as G protein-coupled receptors and ion channels. As such, ion channels and receptors, including G protein-coupled receptors, are common drug targets. OBJECTIVE: We sought to identify, for the first time, ion channels and receptors preferentially expressed by each granulocyte subtype. METHODS: Using GeneChip, we compared approximately 20,000 transcripts present in 7 leukocyte types, platelets, mast cells, and fibroblasts to identify granulocyte subtype-selective transcripts for receptors and ion channels. Granulocyte subtype-selective transcripts were chosen on the basis of several conditions, such as the transcript having a 5-fold or greater expression level compared with the maximum level of other leukocytes. RESULTS: Fifty-one transcripts were chosen to be preferentially expressed by each granulocyte subtype. Seventeen of the 51 transcripts have not been previously reported as granulocyte subtype selective. Among the 17 receptors and ion channels, 6 were basophil selective, eosinophil selective, or both and were not highly expressed by other organs, indicating that they might be potential targets for antiallergy drugs. CONCLUSION: Use of this database of potential cell type-selective drug targets should minimize the efforts required for pharmaceutical development.
Authors: David F Choy; Barmak Modrek; Alexander R Abbas; Sarah Kummerfeld; Hilary F Clark; Lawren C Wu; Grazyna Fedorowicz; Zora Modrusan; John V Fahy; Prescott G Woodruff; Joseph R Arron Journal: J Immunol Date: 2010-12-27 Impact factor: 5.422