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

Abstract

Human CC chemokine receptor 1 (CCR1) has been proposed as a receptor for CKβ8. To obtain conclusive evidence, binding-displacement studies of 125I-CKβ8 (25-99) were performed on membranes of Chinese hamster ovary cells expressing human CCR1. The IC50 for displacement of 125I-CKβ8 (25-99) with CKβ8 (25-99) was 0.22 nM. The longer forms of CKβ8 (24-99 and 1-99) also displaced 125I-CKβ8, with IC50 values of 6.5 and 16 nM, respectively. Displacement profiles of 125I-CKβ8 (25-99) on freshly prepared human monocytes indicated that CCR1 was the major receptor for CKβ8. We conclude that CCR1 is a receptor for different-length CKβ8 and that CKβ8 (25-99) has a similar affinity for CCR1 as macrophage inflammatory protein-1α (MIP-1α). The longer variants of CKβ8 are significantly less potent than CKβ8 (25-99) and MIP-1α on CCR1 and monocytes (P < 0.05). Copyright (C) 2000 Elsevier Science Inc.