title: Chemokines bind to sulfatides as revealed by surface plasmon resonance.
abstract: Chemokines bind to sulfated cell surface glycosaminoglycans and thereby modulate signaling mediated by G-protein-coupled seven-transmembrane domain chemokine receptors. Similar to glycosaminoglycans, sulfated oligosaccharides are also exposed on the cell surface by sulfatides, a class of glycosphingolipids. We have now identified sulfated glycosphingolipids (sulfatides) as novel binding partners for chemokines. Using surface plasmon resonance (SPR), the binding of proinflammatory and homeostatic chemokines to glycosphingolipids, in particular sulfatides, was investigated. Chemokines were immobilized while glycosphingolipids or additional phospholipids incorporated into liposomes were applied as soluble analytes. A specific affinity of the chemokines MCP-1/CCL2, IL-8/CXCL8, SDF-1alpha/CXCL12, MIP-1alpha/CCL3 and MIP-1beta/CCL4 to the sulfatides SM4s, SM3, SM2a and SB2, SB1a was detected. No significant interactions with the chemokines were observed for gangliosides, neutral glycosphingolipids or phospholipids. Chemokine receptors have been associated with the detergent-insoluble fraction supposed to contain 'rafts', i.e., glycosphingolipid enriched microdomains of the cell surface. Accordingly, the data suggest that early chemokine receptor signaling may take place in the vicinity of sulfated glycosphingolipids on the cell surface, whereby these sulfatides could modulate the chemokine receptor-mediated cell activation signal.
authors.affiliation: German Cancer Research Center, Department of Cellular and Molecular Pathology, INF 280, 69120 Heidelberg, Germany. r.sandhoff@dkfz-heidelberg.de
authors.forename: Roger
authors.initials: R
authors.lastname: Sandhoff
authors.forename: Heike
authors.initials: H
authors.lastname: Grieshaber
authors.forename: Roghieh
authors.initials: R
authors.lastname: Djafarzadeh
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: Sijmonsma
authors.forename: Amanda E I
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
authors.forename: Herbert
authors.initials: H
authors.lastname: Wiegandt
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D002772:Cholera Toxin / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D013433:Sulfoglycosphingolipids / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D005732:Gangliosides; D008081:Liposomes; D013433:Sulfoglycosphingolipids; D002772:Cholera Toxin