Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes

Abstract

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.

Liver-Expressed Chemokine/CC Chemokine Ligand 16 Attracts Eosinophils by Interacting with Histamine H4 Receptor

“…H4 has been shown to be primarily expressed by eosinophils and responsible for histamineinduced migration of eosinophils (10,11). In the present study, we have demonstrated that CCL16, which is a low-affinity ligand for CCR1, CCR2, CCR5, and CCR8 (6,8), is also a novel agonist for H4. CCL16 induced vigorous calcium mobilization and chemotaxis through H4 (Figs.…”

“…Liver-expressed chemokine (LEC)/CCL16 (2), also known as novel CC chemokine 4 (2), human CC chemokine 4 (3), lymphocyte and monocyte chemoattractant (4), and liver-specific CC chemokine 1 (5), is selectively expressed in the liver and present in the normal plasma at high concentrations (6). CCL16 was shown to be induced in monocytes by IL-10 (3) and chemotactic for monocytes and lymphocytes (3,4).…”

“…at relatively high concentrations (6), it may be involved in mobilization of eosinophils from the bone marrow. To test this possibility, we injected PBS without or with CCL16 into mice via the tail vein.…”

CCL5/RANTES is important for inducing osteogenesis of human mesenchymal stem cells and is regulated by dexamethasone

“…To explain why CCR1 but not CCL5 knockdown affects the cell numbers during the process of osteogenesis, one reason might be because CCR1 signaling can be activated by several different chemokines in addition to CCL5, such as chemokine (C-C motif) ligand 4 (CCL4), chemokine (C-C motif) ligand 6 (CCL6), chemokine (C-C motif) ligand 14 (CCL14), chemokine (C-C motif) ligand 15 (CCL15), chemokine (C-C motif) ligand 16 (CCL16) and chemokine (C-C motif) ligand 23 (CCL23) (12)(13)(14)(15). There might have other chemokines in addition to CCL5 secreted by hMSCs upon osteogenic induction or present in the fetal calf serum that play a role in maintaining cell numbers during the process of osteogenesis.…”

Intralesional Injection of Adenovirus Encoding CC Chemokine Ligand 16 Inhibits Mammary Tumor Growth and Prevents Metastatic-Induced Death after Surgical Removal of the Treated Primary Tumor

“…In the mouse, only a pseudogene has been identified to date (27,28). CCL16 is a functional ligand for CCR1, CCR2, CCR5 (29), and CCR8 (30). Recombinant CCL16 demonstrated chemotactic activity on human monocytes and lymphocytes (27).…”