title: Liver-expressed chemokine/CC chemokine ligand 16 attracts eosinophils by interacting with histamine H4 receptor.
abstract: Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine that is constitutively expressed by the liver parenchymal cells and present in the normal plasma at high concentrations. Previous studies have shown that CCL16 is a low-affinity ligand for CCR1, CCR2, CCR5, and CCR8 and attracts monocytes and T cells. Recently, a novel histamine receptor termed type 4 (H4) has been identified and shown to be selectively expressed by eosinophils and mast cells. In this study, we demonstrated that CCL16 induced pertussis toxin-sensitive calcium mobilization and chemotaxis in murine L1.2 cells expressing H4 but not those expressing histamine receptor type 1 (H1) or type 2 (H2). CCL16 bound to H4 with a K(d) of 17 nM. By RT-PCR, human and mouse eosinophils express H4 but not H3. Accordingly, CCL16 induced efficient migratory responses in human and mouse eosinophils. Furthermore, the responses of human and mouse eosinophils to CCL16 were effectively suppressed by thioperamide, an antagonist for H3 and H4. Intravenous injection of CCL16 into mice induced a rapid mobilization of eosinophils from bone marrow to peripheral blood, which was also suppressed by thioperamide. Collectively, CCL16 is a novel functional ligand for H4 and may have a role in trafficking of eosinophils.
authors.affiliation: Department of Microbiology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Kunio
authors.initials: K
authors.lastname: Hieshima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagakubo
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kunori
authors.forename: Takao
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D019742:Chemokines, CC / Q000494:pharmacology* / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D007958:Leukocyte Count; D008024:Ligands; D008099:Liver / Q000378:metabolism; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D010802:Phylogeny; D010880:Piperidines / Q000494:pharmacology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000145:classification; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D011968:Receptors, Histamine / Q000187:drug effects* / Q000502:physiology; D018100:Receptors, Histamine H3 / Q000187:drug effects; D000074040:Receptors, Histamine H4; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C481939:CCL16 protein, human; D019742:Chemokines, CC; C418607:HRH4 protein, human; C498829:Hrh4 protein, mouse; D008024:Ligands; D010880:Piperidines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; D011994:Recombinant Proteins; D037342:Pertussis Toxin; C052075:thioperamide