Chemokines exert their biological activity through high-affinity interactions with cell-surface receptors, thereby activating specific signalling pathways, and a second low-affinity interaction with proteoglycans. Proteoglycans consist of a protein core, to which GAG (glycosaminoglycan) chains are attached. The GAGs are long, linear, sulphated and highly charged heterogeneous polysaccharides that are expressed throughout the body in different forms depending on the developmental or pathological state of the organ/organism. Mechanistically, the GAG interaction is thought to facilitate the retention of chemokines on cell surfaces, thereby forming a high local concentration required for cell activation. Recently, we demonstrated that certain chemokines require interactions with GAGs for their in vivo function. Additionally we have shown that chemokines oligomerize on immobilized GAGs, and this ability to form higher order oligomers has also been shown to be essential for the activity of certain chemokines in vivo. We believe that interference with the chemokine–GAG interaction provides a novel anti-inflammatory strategy, exemplified by a variant of RANTES (regulated upon activation, normal T-cell expressed and secreted) that has abrogated GAG binding and oligomerization properties.
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Conference Article|
May 22 2006
The biological relevance of chemokine–proteoglycan interactions
A.E.I. Proudfoot
A.E.I. Proudfoot
1
1Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan-les-Ouates, Geneva, Switzerland
1email amanda.proudfoot@serono.com
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Publisher: Portland Press Ltd
Received:
December 20 2005
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (3): 422–426.
Article history
Received:
December 20 2005
Citation
A.E.I. Proudfoot; The biological relevance of chemokine–proteoglycan interactions. Biochem Soc Trans 1 June 2006; 34 (3): 422–426. doi: https://doi.org/10.1042/BST0340422
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