Interaction of chemokines and glycosaminoglycans: a new twist in the regulation of chemokine function with opportunities for therapeutic intervention.
Despite their key role in inflammation, the apparent redundancy in the chemokine system is often cited as an argument against probing chemokines as therapeutic targets for inflammation. However, this in vitro redundancy frequently does not translate to the in vivo situation, as exemplified by the use of specific receptor antagonists, ligand neutralizing or receptor blocking antibodies and gene-deleted mice in models of human disease. Specificity may be conferred onto the chemokine system by fine-tuning of responses both temporally and spatially through their highly specific interactions with glycosaminoglycans (GAGs). In this survey, we present evidence for specificity in the interaction and introduce emerging technologies that enable detailed assessment of protein-GAG interactions. Finally, we address the issue of exploitation of this interaction for therapeutic advantage.
Celltech, 216 Bath Road, Slough, Berkshire, UK. zoe.johnson@slh.celltechgroup.com
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Johnson
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Proudfoot
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Handel
D018925:Chemokines / Q000378:metabolism*; D016503:Drug Delivery Systems; D006025:Glycosaminoglycans / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy*; D008958:Models, Molecular
D018925:Chemokines; D006025:Glycosaminoglycans