Monocyte chemoattractant protein-2 is a potent agonist of CCR2B.
The binding and functional activity of the CC chemokines monocyte chemoattractant protein-1 (MCP-1), MCP-2, and MCP-3 have been characterized using Chinese hamster ovary DXB-11 cells transfected with the chemokine receptor CCR2B. Receptor binding studies demonstrated that 125I-labeled MCP-1 bound to a single class of high-affinity receptors with a Kd of 0.14 (0.07-0.32) nM. In competition studies MCP-1, MCP-2, and MCP-3 completely inhibited 125I-labeled MCP-1 binding with Ki values of 0.3 (0.16-0.46), 8.8 (3.4-26), and 12.2 (0.6-22) nM, respectively. In calcium mobilization studies, MCP-1 and MCP-3 induced robust elevations in intracellular calcium concentrations, whereas MCP-2 was only weakly active. In contrast, using changes in extracellular acidification rate as a functional readout, all three chemokines were identified as potent agonists of CCR2B. These data demonstrate that MCP-2, in addition to MCP-1 and MCP-3, is a potent agonist of CCR2B and furthermore that MCP-2 activates either different or a subset of the signaling pathways activated by MCP-1 and MCP-3.
Moore
U M
UM
Rhône-Poulenc Rorer Ltd., Dagenham Research Centre, Essex, United Kingdom. Una.Moore@DRC.RP-Rorer.rp.fr
Kaplow
J M
JM
Pleass
R D
RD
Castro
S W
SW
Naik
K
K
Lynch
C N
CN
Daly
S
S
Roach
A G
AG
Jaye
M
M
Williams
R J
RJ
D000818:Animals; D016466:CHO Cells; D054412:Chemokine CCL8; D006224:Cricetinae; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism / Q000494:pharmacology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
C515453:CCL8 protein, human; C515334:CCR2 protein, human; D054412:Chemokine CCL8; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine