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Pharmaceuticals 2017, 10(3), 70; doi:10.3390/ph10030070 (registering DOI)

Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System

Novimmune SA, 1228 Plan-les-Ouates, Switzerland
Novartis Pharma Schweiz A.G., Suurstoffi 14, 6343 Rotkreuz, Switzerland
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA
Authors to whom correspondence should be addressed.
Received: 1 July 2017 / Revised: 24 July 2017 / Accepted: 24 July 2017 / Published: 9 August 2017
(This article belongs to the Special Issue Glycosaminoglycans and Proteoglycans)
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Chemokines have two types of interactions that function cooperatively to control cell migration. Chemokine receptors on migrating cells integrate signals initiated upon chemokine binding to promote cell movement. Interactions with glycosaminoglycans (GAGs) localize chemokines on and near cell surfaces and the extracellular matrix to provide direction to the cell movement. The matrix of interacting chemokine–receptor partners has been known for some time, precise signaling and trafficking properties of many chemokine–receptor pairs have been characterized, and recent structural information has revealed atomic level detail on chemokine–receptor recognition and activation. However, precise knowledge of the interactions of chemokines with GAGs has lagged far behind such that a single paradigm of GAG presentation on surfaces is generally applied to all chemokines. This review summarizes accumulating evidence which suggests that there is a great deal of diversity and specificity in these interactions, that GAG interactions help fine-tune the function of chemokines, and that GAGs have other roles in chemokine biology beyond localization and surface presentation. This suggests that chemokine–GAG interactions add complexity to the already complex functions of the receptors and ligands. View Full-Text
Keywords: chemokines; glycosaminoglycans/GAGs; heparan sulfate; chemokine therapeutics; chemokine structure; chemokine oligomerization chemokines; glycosaminoglycans/GAGs; heparan sulfate; chemokine therapeutics; chemokine structure; chemokine oligomerization

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Proudfoot, A.E.I.; Johnson, Z.; Bonvin, P.; Handel, T.M. Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System. Pharmaceuticals 2017, 10, 70.

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