Identification of C-C chemokine receptor 1 (CCR1) as the monocyte hemofiltrate C-C chemokine (HCC)-1 receptor

• Published in: The Journal of experimental medicine Vol. 188; no. 3; pp. 603 - 608
• Main Authors: Tsou, C L, Gladue, R P, Carroll, L A, Paradis, T, Boyd, J G, Nelson, R T, Neote, K, Charo, I F
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 03.08.1998
• Subjects: Brief Definitive Reports; Cell Line; Chemokine CCL3; Chemokine CCL4; Chemokines, CC - chemical synthesis; Chemokines, CC - metabolism; Chemotaxis; Humans; Macrophage Inflammatory Proteins - metabolism; Monocytes - metabolism; Monocytes - physiology; Receptors, CCR1; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Second Messenger Systems
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.188.3.603

Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1alpha. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1alpha activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1alpha for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1alpha). Similarly, HCC-1 was less potent than MIP-1alpha in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was approximately 100-fold lower than that of MIP-1alpha (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.