The Interaction of Heparin Tetrasaccharides with Chemokine CCL5 Is Modulated by Sulfation Pattern and pH

Singh, Arunima; Kett, Warren C.; Severin, India C.; Agyekum, Isaac; Duan, Jiana; Amster, I. Jonathan; Proudfoot, Amanda E. I.; Coombe, Deirdre R.; Woods, Robert J.

doi:10.1074/jbc.m115.655845

Cited by 56 publications

(69 citation statements)

References 85 publications

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“…5, the orientation of the disaccharide would not be compatible in the context of a longer heparin fragment. Molecular dynamics simulations performed with tetrasaccharides and dodecasaccharides, also suggested that the HS-CCL5 binding interface differs according to the structure and degree of polymerization of the GAG fragments [137]. In the crystal structure, the disaccharide also interacts with both the 30s loop (Ser-31, Gly-32, and Lys-33) and the N terminus (Tyr-3).…”

Section: The 3d Structures Of Chemokine-gag Complexesmentioning

confidence: 95%

The sweet spot: how GAGs help chemokines guide migrating cells

Monneau

Arenzana-Seisdedos

Lortat‐Jacob

2015

Journal of Leukocyte Biology

115

113

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Glycosaminoglycans are polysaccharides that occur both at the cell surface and within extracellular matrices. Through their ability to bind to a large array of proteins, almost 500 of which have been identified to date, including most chemokines, these molecules regulate key biologic processes at the cell-tissue interface. To do so, glycosaminoglycans can provide scaffolds to ensure that proteins mediating specific functions will be presented at the correct site and time and can also directly contribute to biologic activities or signaling processes. The binding of chemokines to glycosaminoglycans, which, at the biochemical level, has been mostly studied using heparin, has traditionally been thought of as a mechanism for maintaining haptotactic gradients within tissues along which cells can migrate directionally. Many aspects of chemokine-glycosaminoglycan interactions, however, also suggest that the formation of these complexes could serve additional purposes that go well beyond a simple immobilization process. In addition, progress in glycobiology has revealed that glycosaminoglycan structures, in term of length, sulfation, and epimerization pattern, are specific for cell, tissue, and developmental stage. Glycosaminoglycan regulation and glycosaminoglycan diversity, which cannot be replicated using heparin, thus suggests that these molecules may fine-tune the immune response by selectively recruiting specific chemokines to cell surfaces. In this context, the aim of the present text is to review the chemokine-glycosaminoglycan complexes described to date and provide a critical analysis of the tools, molecules, and strategies that can be used to structurally and functionally investigate the formation of these complexes.

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Section: The 3d Structures Of Chemokine-gag Complexesmentioning

confidence: 95%

The sweet spot: how GAGs help chemokines guide migrating cells

Monneau

Arenzana-Seisdedos

Lortat‐Jacob

2015

Journal of Leukocyte Biology

115

113

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“…For example, CXCL12 (SDF1) and CCL5 (RANTES) have been shown to directly modulate receptor ligation and leukocyte activation. 69,70 In the absence of HS, the CXCL12γ isoform interacts with sulfotyrosines on its receptor, CXCR4, with higher affinity but with reduced signaling and chemotactic activities, than the CXCL12α isoform. In the presence of HS, CXCL12γ is prevented from interacting with sulfotyrosines on CXCR4, resulting in functional presentation of the chemokine to its receptor and enhanced biological activity of CXCL12γ similar to that of CXCL12α.…”

Section: Pg Interactions With Immunoregulatory Molecules and Immune Cmentioning

confidence: 99%

Proteoglycans as Immunomodulators of the Innate Immune Response to Lung Infection

Kang

Chang

Wight

et al. 2018

J Histochem Cytochem.

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Proteoglycans (PGs) are complex, multifaceted molecules that participate in diverse interactions vital for physiological and pathological processes. As structural components, they provide a scaffold for cells and structural organization that helps define tissue architecture. Through interactions with water, PGs enable molecular and cellular movement through tissues. Through selective ionic interactions with growth factors, chemokines, cytokines, and proteases, PGs facilitate the ability of these soluble ligands to regulate intracellular signaling events and to influence the inflammatory response. In addition, recent findings now demonstrate that PGs can activate danger-associated molecular patterns (DAMPs) and other signaling pathways to influence production of many of these soluble ligands, indicating a more direct role for PGs in influencing the immune response and tissue inflammation. This review will focus on PGs that are selectively expressed during lung inflammation and will examine the novel emerging concept of PGs as immunomodulatory regulators of the innate immune responses in lungs.

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“…We previously showed that GAGs provide fine-tune control of the innate immune response in lungs by controlling the kinetics of chemokine-GAG interactions, chemokine diffusion, and leukocyte migration [9, 10, 112, 113]. Chemokine-GAG interactions are also known to regulate the oligomerization of chemokines in tissues [114, 115] and the ability of chemokines to bind to their high affinity receptor on leukocytes [116, 117]. More recently, studies show that the binding of versican to TLR2 reprograms macrophages and dendritic cells [51, 118].…”

Section: Versican and Hyaluronan As Components In Lung Diseasementioning

confidence: 99%

Interplay of extracellular matrix and leukocytes in lung inflammation

Wight

Frevert

Debley

et al. 2017

Cellular Immunology

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During inflammation, leukocytes influx into lung compartments and interact with extracellular matrix (ECM). Two ECM components, versican and hyaluronan, increase in a range of lung diseases. The interaction of leukocytes with these ECM components controls leukocyte retention and accumulation, proliferation, migration, differentiation, and activation as part of the inflammatory phase of lung disease. In addition, bronchial epithelial cells from asthmatic children co-cultured with human lung fibroblasts generate an ECM that is adherent for monocytes/macrophages. Macrophages are present in both early and late lung inflammation. Matrix metalloproteinase 10 (MMP10) is induced in alveolar macrophages with injury and infection and modulates macrophage phenotype and their ability to degrade collagenous ECM components. Collectively, studies outlined in this review highlight the importance of specific ECM components in the regulation inflammatory events in lung disease. The widespread involvement of these ECM components in the pathogenesis of lung inflammation make them attractive candidates for therapeutic intervention.

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The Interaction of Heparin Tetrasaccharides with Chemokine CCL5 Is Modulated by Sulfation Pattern and pH

Cited by 56 publications

References 85 publications

The sweet spot: how GAGs help chemokines guide migrating cells

The sweet spot: how GAGs help chemokines guide migrating cells

Proteoglycans as Immunomodulators of the Innate Immune Response to Lung Infection

Interplay of extracellular matrix and leukocytes in lung inflammation

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