Selective binding of the truncated form of the chemokine CKbeta8 (25-99) to CC chemokine receptor 1(CCR1).
Human CC chemokine receptor 1 (CCR1) has been proposed as a receptor for CKbeta8. To obtain conclusive evidence, binding-displacement studies of 125I-CKbeta8 (25-99) were performed on membranes of Chinese hamster ovary cells expressing human CCR1. The Ic50 for displacement of 125I-CKbeta8 (25-99) with CKbeta8 (25-99) was 0.22 nM. The longer forms of CKbeta8 (24-99 and 1-99) also displaced 125I-CKbeta8, with Ic50 values of 6.5 and 16 nM, respectively. Displacement profiles of 125I-CKbeta8 (25-99) on freshly prepared human monocytes indicated that CCR1 was the major receptor for CKbeta8. We conclude that CCR1 is a receptor for different-length CKbeta8 and that CKbeta8 (25-99) has a similar affinity for CCR1 as macrophage inflammatory protein-1alpha (MIP-1alpha). The longer variants of CKbeta8 are significantly less potent than CKbeta8 (25-99) and MIP-1a on CCR1 and monocytes (P < 0.05).
Berkhout
T A
TA
Vascular Biology, SmithKline Beecham Pharmaceuticals, Harlow, UK. Theo_Berkhout-1@sbphrd.com
Gohil
J
J
Gonzalez
P
P
Nicols
C L
CL
Moores
K E
KE
Macphee
C H
CH
White
J R
JR
Groot
P H
PH
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D019742:Chemokines, CC / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D007457:Iodine Radioisotopes; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000378:metabolism*; D014162:Transfection
C105504:CCL23 protein, human; C515300:CCR1 protein, human; D019742:Chemokines, CC; D007457:Iodine Radioisotopes; D010455:Peptides; D054389:Receptors, CCR1; D019707:Receptors, Chemokine