Receptor reserve analysis of the human CCR3 receptor in eosinophils and CCR3-transfected cells

A novel pharmacological study of CCR3 receptor reserve in a CCR3-transfecte d cell (CREM3) and human eosinophils was done; functional responses measure d were increases in intracellular calcium and chemotaxis, Eotaxin, eotaxin- 2, monocyte chemoattractant. protein-4 (MCP-4), RANTES, and MCP-S induced s imilar maximal eosinophil chemotaxis, whereas MCP-3 and RANTES induced subm aximal calcium responses in eosinophils compared to eotaxin, MCP-4, and eot axin-2. This suggested a receptor reserve in the chemotaxis response. Recep tor reserve was quantitated for eotaxin, Occupancy of all CCR3 receptors Tv as required for a maximal calcium response in both CREM3 and eosinophils (r eserve 1.0 or 0.17, respectively); the stimulus-calcium response relationsh ip 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 CC R3 interacts with G-proteins that are poorly coupled to the calcium respons e, whereas coupling efficiency and/or amplification to the chemotaxis appar atus in human eosinophils is significantly greater.