Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils
✍ Scribed by Luo Ling Xu; Daniel W. McVicar; Adit Ben-Baruch; Douglas B. Kuhns; James Johnston; Joost J. Oppenheim; Ji Ming Wang
- Book ID
- 102829258
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 664 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils
The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit highaffinity binding for lZ5I-MCP3 with an estimated Kd of 1-3 nM and about 10000 binding sites/cell. The binding of '251-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)la (Kd = 5-10 nM), RANTES (Kd = 5-10 nM), MCPl (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIPlP (Kd > 100 nM).
On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIPla, RANTES, MCPl and MIPlP as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIPla and RAN-TES. However, MIPla and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCPl partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIPla, RANTES and MCP1. The unidirectional competition for MIPlP binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1P. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor.