MONOCYTE CHEMOTACTIC PROTEIN MCP-2 ACTIVATES HUMAN BASOPHIL AND EOSINOPHIL LEUKOCYTES SIMILAR TO MCP-3

It has been shown that CC chemokines activate basophil and eosinophil leukocytes with different selectivities and patterns of activity. The most effective are monocyte chemotactic protein-1 (MCP-1), a potent st imulus of mediator release in basophils without effects on eosinophils , RANTES, a weak stimulus of release and strong chemoattractant for ba sophils and eosinophils, and MCP-3, which combines the activities of M CP-1 and RANTES. We have now compared MCP-2, which has 62 and 60% of s equence identity with MCP-1 and MCP-3, respectively, with the other CC chemokines. MCP-2 induced mediator release by human basophils with lo wer efficacy and potency than MCP-1 and MCP-3. It promoted transient c hanges of cytosolic-free calcium concentration (ICa2+](i)) and chemota ctic responses in both basophils and eosinophils, however somewhat les s efficiently than MCP-3 and RANTES. Desensitization studies indicate that MCP-2 interacts with receptors recognizing MCP-1 as well as RANTE S. These results demonstrate that MCP-2 and MCP-3 exert qualitatively similar biologic activities on basophils and eosinophils. In basophils that had not been treated with IL-3, MCP-2 induced minimal exocytosis only, but desensitized the cells toward MCP-1 and MCP-3, suggesting t hat MCP-2 may act as a functional inhibitor of CC chemokine actions. T he results of this study further indicate that MCP analogues display p artially distinct, partially overlapping bioactivities toward eosinoph ils and basophils, and may thus regulate inflammatory processes involv ing these effector cell types.