ArticleInternational journal of molecular sciences2017
Glycosaminoglycan-Mediated Downstream Signaling of CXCL8 Binding to Endothelial Cells.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- The Role of Cytokines in Vascular Endothelial Glycocalyx Integrity and Impairment Following Open-Heart Surgery.Biomedicines · 2026Review
- Glycosaminoglycan binding to soluble CX3CL1 impacts monocyte migrationFrontiers in immunology · 2026Article
- Pre-bypass ultrafiltration reduces cytokine burden of blood prime in pediatric cardiac surgery.Scientific reports · 2025Observational
- Benchmarking Water Models in Molecular Dynamics of Protein-Glycosaminoglycan Complexes.Journal of chemical information and modeling · 2024Article
- CXCR2 chemokine receptor - a master regulator in cancer and physiology.Trends in molecular medicine · 2024Review
- Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs.International journal of molecular sciences · 2023Article
- Syndecan-4 is the key proteoglycan involved in mediating sepsis-associated lung injury.Heliyon · 2023Article
- Solvent Model Benchmark for Molecular Dynamics of Glycosaminoglycans.Journal of chemical information and modeling · 2023Article
- Studying specificity in protein-glycosaminoglycan recognition with umbrella sampling.Beilstein journal of organic chemistry · 2023Article
- Modeling Protein-Glycosaminoglycan Complexes: Does the Size Matter?Journal of chemical information and modeling · 2021Article
- Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease.Frontiers in molecular biosciences · 2021Review
- Structural Insights Into How Proteoglycans Determine Chemokine-CXCR1/CXCR2 Interactions: Progress and Challenges.Frontiers in immunology · 2020Review
- Structural basis of chemokine interactions with heparan sulfate, chondroitin sulfate, and dermatan sulfate.The Journal of biological chemistry · 2019Article
- Lysines and Arginines play non-redundant roles in mediating chemokine-glycosaminoglycan interactions.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recruitment of leukocytes, mediated by endothelium bound chemokine gradients, is a vital process in inflammation. The highly negatively charged, unbranched polysaccharide family of glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate mediate chemokine immobilization. Specifically the binding of CXCL8 (interleukin 8) to GAGs on endothelial cell surfaces is known to regulate neutrophil recruitment. Currently, it is not clear if binding of CXCL8 to GAGs leads to endothelial downstream signaling in addition to the typical CXCR1/CXCR2 (C-X-C motif chemokine receptor 1 and 2)-mediated signaling which activates neutrophils. Here we have investigated the changes in protein expression of human microvascular endothelial cells induced by CXCL8. Tumor necrosis factor alpha (TNFα) stimulation was used to mimic an inflammatory state which allowed us to identify syndecan-4 (SDC4) as the potential proteoglycan co-receptor of CXCL8 by gene array, real-time PCR and flow cytometry experiments. Enzymatic GAG depolymerization via heparinase III and chondroitinase ABC was used to emulate the effect of glycocalyx remodeling on CXCL8-induced endothelial downstream signaling. Proteomic analyses showed changes in the expression pattern of a number of endothelial proteins such as Zyxin and Caldesmon involved in cytoskeletal organization, cell adhesion and cell mobility. These results demonstrate for the first time a potential role of GAG-mediated endothelial downstream signaling in addition to the well-known CXCL8-CXCR1/CXCR2 signaling pathways in neutrophils.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.