title: Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells.
abstract: Direct contacts between dendritic cells (DCs) and T cells or natural killer T (NKT) cells play important roles in primary and secondary immune responses. SR-PSOX/CXC chemokine ligand 16 (CXCL16), which is selectively expressed on DCs and macrophages, is a scavenger receptor for oxidized low-density lipoprotein and also the chemokine ligand for a G protein-coupled receptor CXC chemokine receptor 6 (CXCR6), expressed on activated T cells and NKT cells. SR-PSOX/CXCL16 is the second transmembrane-type chemokine with a chemokine domain fused to a mucin-like stalk, a structure very similar to that of fractalkine (FNK). Here, we demonstrate that SR-PSOX/CXCL16 functions as a cell adhesion molecule for cells expressing CXCR6 in the same manner that FNK functions as a cell adhesion molecule for cells expressing CX(3)C chemokine receptor 1 (CX(3)CR1) without requiring CX(3)CR1-mediated signal transduction or integrin activation. The chemokine domain of SR-PSOX/CXCL16 mediated the adhesion of CXCR6-expressing cells, which was not impaired by treatment with pertussis toxin, a Galphai protein blocker, which inhibited chemotaxis of CXCR6-expressing cells induced by SR-PSOX/CXCL16. Furthermore, the adhesion activity was up-regulated by treatment of SR-PSOX/CXCL16-expressing cells with a metalloprotease inhibitor, which increased surface expression levels of SR-PSOX/CXCL16. Thus, SR-PSOX/CXCL16 is a unique molecule that not only attracts T cells and NKT cells toward DCs but also supports their firm adhesion to DCs.
authors.affiliation: Kyoto University, Shogoin Kawahara-cho 53, Sakyo-ku, Kyoto 606-8507, Japan. syonehar@virus.kyoto-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimaoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Fukumoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kume
authors.forename: Shu
authors.initials: S
authors.lastname: Takahashi
authors.forename: Junko
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: Manabu
authors.initials: M
authors.lastname: Minami
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Hayashida
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Jun
authors.initials: J
authors.lastname: Ohsumi
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.forename: Shin
authors.initials: S
authors.lastname: Yonehara
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D045726:Metalloproteases / Q000037:antagonists & inhibitors; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011991:Receptors, Virus
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D015815:Cell Adhesion Molecules; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D037342:Pertussis Toxin; D045726:Metalloproteases