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 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.
Nomiyama
H
H
Department of Biochemistry, Kumamoto University Medical School, Honjo, Kumamoto 860-0811, Japan.
Hieshima
K
K
Nakayama
T
T
Sakaguchi
T
T
Fujisawa
R
R
Tanase
S
S
Nishiura
H
H
Matsuno
K
K
Takamori
H
H
Tabira
Y
Y
Yamamoto
T
T
Miura
R
R
Yoshie
O
O
D000818:Animals; D020013:Calcium Signaling / Q000276:immunology; D002460:Cell Line; D019742:Chemokines, CC / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D002633:Chemotaxis / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells; D008024:Ligands; D008099:Liver / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
C481939:CCL16 protein, human; C515300:CCR1 protein, human; C515334:CCR2 protein, human; C515301:Ccr1 protein, mouse; C515335:Ccr2 protein, mouse; D019742:Chemokines, CC; D008024:Ligands; D012333:RNA, Messenger; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine