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

Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine selectively e xpressed in the liver. Here, we investigated its receptor usage by calcium mobilization and chemotactic assays using mouse L1.2 pre-B cell lines stabl y expressing a panel of 12 human chemokine receptors. At relatively high co ncentrations, LEG induced calcium mobilization and chemotaxis via CCR1 and CCR2. LEG also induced calcium mobilization, but marginal chemotaxis via CC R5. Consistently, LEG was found to bind to CCR1, CCR2 and CCR5 with relativ ely low affinities. The binding of LEG to CCR8 was much less significant. I n spite of its binding to CCR5, LEG was unable to inhibit infection of an R 5-type HIV-1 to activated human peripheral blood mononuclear cells even at high concentrations. In human liver sections, hepatocytes were strongly sta ined by anti-LEC antibody. HepG2, a human hepatocarcinoma cell line, was fo und to constitutively express LEC. LEG was also present in the plasma sampl es from healthy adult donors at relatively high concentrations (0.3-4 nM). Taken together, LEG is a new low-affinity functional ligand for CCR1, CCR2 and CCR5, and is constitutively expressed by liver parenchymal cells. The p resence of LEG in normal plasma at relatively high concentrations may modul ate inflammatory responses.