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    Abstract:
    Abstract Chemokine receptor/ligand interactions orchestrate the migration of cells to peripheral tissues such as the skin. We analysed chemokine receptor expression by acute myeloid leukaemic (AML) cells present in peripheral blood (n = 7), bone marrow (n = 6), or skin (n = 11) obtained from 15 paediatric AML patients with skin involvement and in 10 AML patients without skin involvement. High percentages of circulating CCR2 pos AML cells were only detected in patients with extramedullary disease. Skin‐residing AML cells displayed a different set of receptors in situ, namely: CCR5, CXCR4, CXCR7 and CX3CR1. These results suggest the involvement of different chemokine/chemokine receptor interactions in homing and retention of AML blasts in the skin. Pediatr Blood Cancer. 2010;55:344–348. © 2010 Wiley–Liss, Inc.
    Keywords:
    CX3CR1
    CCR2
    Chemokine receptor CCR5
    CC chemokine receptors
    CCR1
    CCL3
    CCR1
    CCR3
    Macrophage inflammatory protein
    Chemokine receptor CCR5
    CCR2
    CCL13
    CCL3
    CXCL2
    CCL21
    XCL2
    CCL22
    CCR5,as the member of CC receptor family,with its ligands being CCL3(MIP-1α),CCL4(MIP-1β) and CCL5(RANTES),is categorized as 7 trans-membrane domain G-protein coupled receptor.CCR5 is expressed in monocytes/macrophages as well as lymphocytes inducing chemotaxis and recruitment in inflammatory response and is an important co-receptor of human immunodeficiency virus(HIV)-1 virus,leading to the multifunction of CCR5 in progression of various kind of immunological diseases and invasion of HIV-1.Moreover,the expression of CCR5 on the surface of tumor cells and stromal cells contributes to mediating multiple biological behaviors of cancers such as proliferation and invasion.Advanced technologies also lead to the revealing of structure,function,signal transduction and roles of CCR5 in the progression of related diseases.
    CCL5
    Chemokine receptor CCR5
    CCR1
    CC chemokine receptors
    CCL7
    CCL3
    CCL21
    Citations (1)
    CCL5
    Chemokine receptor CCR5
    CCL21
    CCR1
    CCL3
    XCL2
    CCL13
    CC chemokine receptors
    CCL7
    CCL17
    CXCL16
    CXCL2
    CCR2
    Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine selectively expressed in the liver. Here, we investigated its receptor usage by calcium mobilization and chemotactic assays using mouse L1.2 pre-B cell lines stably expressing a panel of 12 human chemokine receptors. At relatively high concentrations, LEC induced calcium mobilization and chemotaxis via CCR1 and CCR2. LEC also induced calcium mobilization, but marginal chemotaxis via CCR5. Consistently, LEC was found to bind to CCR1, CCR2 and CCR5 with relatively low affinities. The binding of LEC to CCR8 was much less significant. In spite of its binding to CCR5, LEC was unable to inhibit infection of an R5-type HIV-1 to activated human peripheral blood mononuclear cells even at high concentrations. In human liver sections, hepatocytes were strongly stained by anti-LEC antibody. HepG2, a human hepatocarcinoma cell line, was found to constitutively express LEC. LEC was also present in the plasma samples from healthy adult donors at relatively high concentrations (0.3--4 nM). Taken together, LEC is a new low-affinity functional ligand for CCR1, CCR2 and CCR5, and is constitutively expressed by liver parenchymal cells. The presence of LEC in normal plasma at relatively high concentrations may modulate inflammatory responses.
    CCR1
    CC chemokine receptors
    Chemokine receptor CCR5
    CCR2
    CCL25
    XCL2
    CCL13
    CXCL2
    CXCL16
    CCL21
    Citations (95)
    Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1α. 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-1α 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-1α for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1α). Similarly, HCC-1 was less potent than MIP-1α 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 ∼100-fold lower than that of MIP-1α (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.
    CCR1
    CC chemokine receptors
    Chemokine receptor CCR5
    CCL13
    CCL17
    Citations (62)