Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin.
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.
Uguccioni
M
M
Theodor Kocher Institute, University of Bern, Switzerland.
Loetscher
P
P
Forssmann
U
U
Dewald
B
B
Li
H
H
Lima
S H
SH
Li
Y
Y
Kreider
B
B
Garotta
G
G
Thelen
M
M
Baggiolini
M
M
D000118:Acetylglucosaminidase / Q000097:blood; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D054413:Chemokine CCL11; D054410:Chemokine CCL7; D018925:Chemokines / Q000494:pharmacology; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D003001:Cloning, Molecular; D016207:Cytokines / Q000737:chemistry* / Q000494:pharmacology; D017931:DNA Primers; D018076:DNA, Complementary; D005333:Fetus; D015723:Gene Library; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
C515456:CCL11 protein, human; C099677:CCL13 protein, human; C515450:CCL7 protein, human; D054413:Chemokine CCL11; D054410:Chemokine CCL7; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; D018945:Monocyte Chemoattractant Proteins; D010446:Peptide Fragments; D000118:Acetylglucosaminidase