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Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B.

The CC chemokine monocyte chemoattractant protein-3 (MCP-3) activates human monocytes, lymphocytes, basophils, and eosinophils. MCP-3 has been reported to induce [Ca2+]i changes in cells transfected with the monocyte-selective MCP-1 receptor 2B (CC CKR2B) and competes for 125I-MCP-1 binding on CC CKR2B, suggesting that it may mediate monocyte responses to MCP-3. However, we now show that MCP-3 is a ligand and potent agonist for the macrophage inflammatory protein-1 alpha (MIP-1 alpha)/regulated on activation, normal T expressed, and secreted protein (RANTES) receptor CC CKR1 (rank order for [Ca2+]i changes = MIP-1 alpha > MCP-3 > RANTES), which is expressed in monocytes > neutrophils > eosinophils. 125I-MCP-3 bound directly to CC CKR1 and CC CKR2B (Ki = 8 and 7 nM, respectively). Binding to CC CKR1 was competed by all CC chemokines tested except MCP-1. In contrast, binding to CC CKR2B was competed only by MCP-3 and MCP-1. Both MCP-1 and MCP-3 were equipotent agonists (EC50 = 10 nM for [Ca2+]i changes). Thus, MCP-3 is a functional ligand for both CC CKR1 and CC CKR2B, which otherwise have distinct selectivities for CC chemokines. These data suggest that monocyte responses to MCP-3 could be mediated by both CC CKR2B and CC CKR1, whereas eosinophil responses to MCP-3 could be mediated by CC CKR1.

Pubmed ID: 8530354

Authors

  • Combadiere C
  • Ahuja SK
  • Van Damme J
  • Tiffany HL
  • Gao JL
  • Murphy PM

Journal

The Journal of biological chemistry

Publication Data

December 15, 1995

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Basophils
  • Binding, Competitive
  • Chemokine CCL7
  • Chemokines
  • Cytokines
  • Eosinophils
  • Humans
  • Iodine Radioisotopes
  • Kinetics
  • Leukocytes
  • Ligands
  • Lymphocytes
  • Molecular Sequence Data
  • Monocyte Chemoattractant Proteins
  • Monocytes
  • Radioligand Assay
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Recombinant Proteins
  • Time Factors