Selective binding of the truncated form of the chemokine CKβ8 (25-99) to CC chemokine receptor 1 (CCR1)

Human CC chemokine receptor 1 (CCR1) has been proposed as a receptor for CK beta 8. To obtain conclusive evidence, binding-displacement studies of I-125-CK beta 8 (25-99) were performed on membranes of Chinese hamster ovary cells expressing human CCR1. The IC50 for displacement of I-125-CK beta 8 (25-99) with CK beta 8 (25-99) was 0.22 nM. The longer forms of CK beta 8 (24-99 and 1-99) also displaced I-125-CK beta 8, with IC50 values of 6.5 and 16 nM, respectively. Displacement profiles of I-125-CK beta 8 (25-99) on freshly prepared human monocytes indicated that CCR1 was the major receptor for CK beta 8. We conclude that CCR1 is a receptor for different-length CK beta 8 and that CK beta 8 (25-99) has a similar affinity for CCR1 as macrophage inflammatory protein-1 alpha (MIP-1 alpha). The longer variants CK beta 8 are significantly less potent than CK beta 8 (25-99) and MIP-1 alpha on CCR1 and monocytes (P < 0.05). (C) 2000 Elsevier Science Inc.