Chemokine interaction with synergy-inducing molecules: fine tuning modulation of cell trafficking

Cecchinato, Valentina; D’Agostino, Gianluca; Raeli, Lorenzo; Uguccioni, Mariagrazia

doi:10.1189/jlb.1mr1015-457r

Cited by 27 publications

(28 citation statements)

References 66 publications

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“…51–53). Several reports have succeeded in demonstrating a positive effect of chemokine synergism in various in vivo models, including mouse models of monocyte recruitment to atherosclerotic lesions (61), neutrophil recruitment to the peritoneum (62), and rat models of leukocyte recruitment to inflamed skin (63) and the CNS (64).…”

Section: Discussionmentioning

confidence: 99%

Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4

et al. 2017

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The chemokine receptor, CXC chemokine receptor 4 (CXCR4), is selective for CXC chemokine ligand 12 (CXCL12), is broadly expressed in blood and tissue cells, and is essential during embryogenesis and hematopoiesis. CXCL14 is a homeostatic chemokine with unknown receptor selectivity and preferential expression in peripheral tissues. Here, we demonstrate that CXCL14 synergized with CXCL12 in the induction of chemokine responses in primary human lymphoid cells and cell lines that express CXCR4. Combining subactive concentrations of CXCL12 with 100–300 nM CXCL14 resulted in chemotaxis responses that exceeded maximal responses that were obtained with CXCL12 alone. CXCL14 did not activate CXCR4-expressing cells (i.e., failed to trigger chemotaxis and Ca2+ mobilization, as well as signaling via ERK1/2 and the small GTPase Rac1); however, CXCL14 bound to CXCR4 with high affinity, induced redistribution of cell-surface CXCR4, and enhanced HIV-1 infection by >3-fold. We postulate that CXCL14 is a positive allosteric modulator of CXCR4 that enhances the potency of CXCR4 ligands. Our findings provide new insights that will inform the development of novel therapeutics that target CXCR4 in a range of diseases, including cancer, autoimmunity, and HIV.—Collins, P. J., McCully, M. L., Martínez-Muñoz, L., Santiago, C., Wheeldon, J., Caucheteux, S., Thelen, S., Cecchinato, V., Laufer, J. M., Purvanov, V., Monneau, Y. R., Lortat-Jacob, H., Legler, D. F., Uguccioni, M., Thelen, M., Piguet, V., Mellado, M., Moser, B. Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4.

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Section: Discussionmentioning

confidence: 99%

Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4

et al. 2017

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“…However, HMGB1 attenuates the chemotactic responses of mouse embryonic fibroblasts to the chemokine CXCL12 by blocking the receptor CXCR4 or neutralizing CXCL12, suggesting that the action of HMGB1 requires the expression of cell surface CXCR4 as well as the concomitant presence of CXCL12. 6,158,159 Interestingly, HMGB1 and CXCL12 form heterocomplexes and exhibit a monocyte chemotactic activity that is more potent than that of CCXL12 alone. Mechanistically, HMGB1 increases binding of CXCL12 to CXCR4 by fixing its N-terminal domain in a conformation that is better suited for receptor activation.…”

Section: The Fine-tuned Orchestration Of Chemokine Synergy In the Infmentioning

confidence: 99%

“…Mechanistically, HMGB1 increases binding of CXCL12 to CXCR4 by fixing its N-terminal domain in a conformation that is better suited for receptor activation. 6,160 Some chemokine ligands possess sugar moieties that bind lycosaminoglycans (GAGs), which immobilize chemokines on the endothelial surface to ensure the directionality of the chemotactic signals for leukocytes. [161][162][163] Chemokines that fail to be immobilized by endothelial GAGs may either be dispersed from the production site or diluted to concentrations below the receptor activating threshold, thereby reducing leukocyte extravasation into tissues.…”

Section: The Fine-tuned Orchestration Of Chemokine Synergy In the Infmentioning

confidence: 99%

Chemokines in homeostasis and diseases

et al. 2018

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For the past twenty years, chemokines have emerged as a family of critical mediators of cell migration during immune surveillance, development, inflammation and cancer progression. Chemokines bind to seven transmembrane G protein-coupled receptors (GPCRs) that are expressed by a wide variety of cell types and cause conformational changes in trimeric G proteins that trigger the intracellular signaling pathways necessary for cell movement and activation. Although chemokines have evolved to benefit the host, inappropriate regulation or utilization of these small proteins may contribute to or even cause diseases. Therefore, understanding the role of chemokines and their GPCRs in the complex physiological and diseased microenvironment is important for the identification of novel therapeutic targets. This review introduces the functional array and signals of multiple chemokine GPCRs in guiding leukocyte trafficking as well as their roles in homeostasis, inflammation, immune responses and cancer.

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“…Both in vitro and in vivo studies have shown that FSP-ZM1 blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ-42-induced cellular stress in RAGE-expressing cells and in the mouse brain [21]. It was recently demonstrated that HMGB1 is an enhancer of the activity of CXCL12 in stimulating the migration of mouse embryonic fibroblast [22].…”

Section: Discussionmentioning

confidence: 99%

A novel full-reduced HMGB1 and kartogenin-containing bio-active scaffold for meniscus regeneration

Zhi-hong

Zou

et al. 2020

Preprint

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43 44 A novel bio-active scaffold for enhancing wounded meniscus healing has been developed by 45 combination of High mobility group box 1 protein (HMGB1) and kartogenin (KGN) with 46 alginate gel. The properties of the bio-active scaffold were also investigated using an in vitro cell 47 culture model and in vivo rat wounded meniscus healing model. This HMGB1-KGN-containing 48 bioactive scaffold released HMGB1 and KGN into wound area and kept high concentrations of 49 HMGB1 and KGN in the system for more than two weeks. This HMGB1-KGN-containing 50 bioactive scaffold also activated rat bone marrow stem cells (BMSCs) from G0 to GAlert stage and 51 promoted cell proliferation as evidenced by 5-bromo-2-deoxyuridine (BrdU) incorporation 52 testing. Our results also demonstrated that the HMGB1-KGN-containing bioactive scaffold 53 induced cell migration in vitro and recruited the cells to wound area to promote wounded rat 54 meniscus healing in vivo. 55 56 57 58 59 60 61 62 63 64 4 65 66 67The menisci are C-shaped fibrocartilage located between the femoral condyles and tibial plateau 68 to transmit the load across the joint space [1]. Menisci play an important role in joint 69 stabilization, proprioception, lubrication and protection of articular cartilage [2]. Such 70 environment and function lead to meniscus easily injury and damaged meniscus can cause the 71 progression of cartilage degeneration and result in osteoarthritis [3]. Clinical studies have found 72 that it is difficult to regenerate the meniscus due to the specific structural and functional 73 properties of the meniscus tissue [1]. 74 75Histology studies have shown that meniscus is a geometrically and biochemically complex tissue. 76Its outer 1/3 tissue is formed by collagen type I produced by fibroblast-like cells, while its inner 77 2/3 tissue is formed by collagen II and proteoglycan produced by chondrocyte-like cells [4]. 78 Vascularization in meniscus is of high relevance. The meniscus is fully vascularized during fetal 79 development though blood supply diminishes over time, receding to the peripheral 20-30% by 10 80 years of age [4], [1]. 81 82The injury in the avascular zone of the meniscus is generally more complex and broad, and is 83 often associated with a poor prognosis following repair [5]. Promoting the healing process in the 84 avascular zone of the meniscus is an ongoing challenge for both clinical medical doctors and 85 orthopedic researchers [6]. Recently, tissue engineering approaches that involve the use of adult 86 tissue-derived multi-potent stem cells and biomaterial scaffolds have gained increasing attention 87 5 for enhancing the wounded meniscus healing. However, the isolation and culture of stem cells 88 not only need the donor tissue obtained by additional surgical procedure but also take long time 89 and increase contamination risk. Therefore, recruiting stem cells to wound area to enhance 90 wound healing is still a new challenge for orthopedic researchers. 91 92 High mobility group box 1 protein (HMGB1) is a ubiquitously...

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Chemokine interaction with synergy-inducing molecules: fine tuning modulation of cell trafficking

Abstract: Review on synergistic activities induced by heterocomplexes formed with chemokines.

Cited by 27 publications

References 66 publications

Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4

Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4

Chemokines in homeostasis and diseases

A novel full-reduced HMGB1 and kartogenin-containing bio-active scaffold for meniscus regeneration

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