Receptor reserve analysis of the human CCR3 receptor in eosinophils and CCR3-transfected cells
| Autor: | M. Motasim Billah, Yuntao Wan, Fang Tian, Jennifer Shortall, James Jakway, Himanshu Shah, Robert W. Egan, Charles G. Garlisi, Shelby P. Umland |
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| Rok vydání: | 2000 |
| Předmět: |
Chemokine CCL11
Eotaxin Chemotactic Factors Eosinophil Receptors CCR3 Immunology CCR3 chemistry.chemical_element Biology Calcium Ligands Transfection Binding Competitive Calcium in biology Cell Line immune system diseases Animals Humans Immunology and Allergy Calcium Signaling Receptor Chemokine CCL5 Cells Cultured Dose-Response Relationship Drug hemic and immune systems Chemotaxis Cell Biology respiratory system Monocyte Chemoattractant Proteins Rats Cell biology Eosinophils Chemotaxis Leukocyte Interleukin 10 chemistry Chemokines CC Eosinophil chemotaxis Cytokines Thermodynamics Receptors Chemokine |
| Zdroj: | Journal of Leukocyte Biology. 67:441-447 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | A novel pharmacological study of CCR3 receptor reserve in a CCR3-transfected cell (CREM3) and human eosinophils was done; functional responses measured were increases in intracellular calcium and chemotaxis. Eotaxin, eotaxin-2, monocyte chemoattractant protein-4 (MCP-4), RANTES, and MCP-3 induced similar maximal eosinophil chemotaxis, whereas MCP-3 and RANTES induced submaximal calcium responses in eosinophils compared to eotaxin, MCP-4, and eotaxin-2. This suggested a receptor reserve in the chemotaxis response. Receptor reserve was quantitated for eotaxin. Occupancy of all CCR3 receptors was required for a maximal calcium response in both CREM3 and eosinophils (reserve = 1.0 or 0.17, respectively); the stimulus-calcium response relationship was linear, indicating no receptor reserve. In contrast, in eosinophils a large receptor reserve (6.5) was found for chemotaxis, where occupancy of 15% receptors drove half-maximal responses. These studies indicate that CCR3 interacts with G-proteins that are poorly coupled to the calcium response, whereas coupling efficiency and/or amplification to the chemotaxis apparatus in human eosinophils is significantly greater. J. Leukoc. Biol. 67: 441–447; 2000. |
| Databáze: | OpenAIRE |
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