Chemokines bind to sulfatides as revealed by surface plasmon resonance.
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.
Sandhoff
Roger
R
German Cancer Research Center, Department of Cellular and Molecular Pathology, INF 280, 69120 Heidelberg, Germany. r.sandhoff@dkfz-heidelberg.de
Grieshaber
Heike
H
Djafarzadeh
Roghieh
R
Sijmonsma
Tjeerd P
TP
Proudfoot
Amanda E I
AE
Handel
Tracy M
TM
Wiegandt
Herbert
H
Nelson
Peter J
PJ
Gröne
Hermann-Josef
HJ
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
D018932:Chemokine CCL2; D018925:Chemokines; D005732:Gangliosides; D008081:Liposomes; D013433:Sulfoglycosphingolipids; D002772:Cholera Toxin