Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin

J Exp Med. 1996 May 1;183(5):2379-84. doi: 10.1084/jem.183.5.2379.

Abstract

A novel human CC chemokine complementary DNA was identified in a library constructed from human fetal RNA, cloned into a baculovirus vector, and expressed in Sf9 insect cells. The mature recombinant protein that was released had the NH2-terminal sequence pyro-QPDALNVPSTC...and consisted of 75 amino acids. Minor amounts of two variants of 77 and 82 residues (NH2 termini: LAQPDA...and FNPQGLAQPDA...) were released as well. The novel chemokine was designated monocyte chemotactic protein 4 (MCP-4) and the variants were designated (LA)MCP-4 and (FNPQGLA)MCP-4. MCP-4 shares the pyroglutamic acidproline NH2-terminal motif and 56-61% sequence identity with the three known monocyte chemotactic proteins and is 60% identical to eotaxin. It has marked functional similarities to MCP-3 and eotaxin. Like MCP-3, MCP-4 is a chemoattractant of high efficacy for monocytes and T lymphocytes. On these cells, it binds to receptors that recognize MCP-1, MCP-3, and RANTES. On eosinophils, MCP-4 has similar efficacy and potency as MCP-3, RANTES, and cotaxin. It shares receptors with eotaxin and shows full cross-desensitization with this cosinophil-selective chemokine. Of the two variants, only (LA)MCP-4 could be purified in sufficient quantities for testing and was found to be at least 30-fold less potent than MCP-4 itself. This suggests that the 75-residue form with the characteristic NH2 terminus of an MCP is the biologically relevant species.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / blood
  • Amino Acid Sequence
  • Base Sequence
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / physiology
  • Chemokine CCL11
  • Chemokine CCL7
  • Chemokines / pharmacology
  • Chemokines, CC*
  • Chemotaxis, Leukocyte*
  • Cloning, Molecular
  • Cytokines / chemistry*
  • Cytokines / pharmacology
  • DNA Primers
  • DNA, Complementary
  • Fetus
  • Gene Library
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Leukocytes / drug effects
  • Leukocytes / physiology*
  • Molecular Sequence Data
  • Monocyte Chemoattractant Proteins / biosynthesis*
  • Monocyte Chemoattractant Proteins / chemistry*
  • Monocyte Chemoattractant Proteins / pharmacology*
  • Monocytes / physiology
  • Neutrophils / physiology
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Polymerase Chain Reaction
  • Sequence Homology, Amino Acid

Substances

  • CCL11 protein, human
  • CCL13 protein, human
  • CCL7 protein, human
  • Chemokine CCL11
  • Chemokine CCL7
  • Chemokines
  • Chemokines, CC
  • Cytokines
  • DNA Primers
  • DNA, Complementary
  • Monocyte Chemoattractant Proteins
  • Peptide Fragments
  • Acetylglucosaminidase