A5036901624- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Proteoglycans and glycosaminoglycans research
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Immune cells in cancer
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Immunotherapy and Immune Responses
- Inflammatory mediators and NSAID effects
- Osteoarthritis Treatment and Mechanisms
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Cancer, Stress, Anesthesia, and Immune Response
- Heparin-Induced Thrombocytopenia and Thrombosis
- Traumatic Brain Injury and Neurovascular Disturbances
- Adenosine and Purinergic Signaling
- Immune Cell Function and Interaction
- Macrophage Migration Inhibitory Factor
- Neurological Disease Mechanisms and Treatments
- Barrier Structure and Function Studies
- Advanced Biosensing Techniques and Applications
- vaccines and immunoinformatics approaches
- Neuroinflammation and Neurodegeneration Mechanisms
University of Manchester
2011-2025
Wellcome Centre for Cell-Matrix Research
2014-2024
Manchester Academic Health Science Centre
2018-2024
National Health Service
2023
University of Glasgow
2016-2022
Institute of Infection and Immunity
2022
Centre for Inflammation Research
2021
University of California, San Diego
2014-2019
University of Montana
2014-2017
Abstract TNF-stimulated gene/protein-6 (TSG-6) is expressed by many different cell types in response to proinflammatory cytokines and plays an important role the protection of tissues from damaging consequences acute inflammation. Recently, TSG-6 was identified as being largely responsible for beneficial effects multipotent mesenchymal stem cells, example treatment animal models myocardial infarction corneal injury/allogenic transplant. The protective effect due part its inhibition...
Highlights•Mice deficient in CCR1, CCR2, CCR3, and CCR5 (iCCRs) develop normally•iCCRs redundantly establish resting tissue-resident myelomonocytic cell populations•CCR2 dominates controlling monocyte recruitment acute inflammation•iCCRs are not involved neutrophil or lymphocyte inflammationSummaryCurrently, we lack an understanding of the individual combinatorial roles for chemokine receptors inflammatory process. We report studies on mice with a compound deletion Ccr1, Ccr2, Ccr3, Ccr5,...
Both chemokine oligomerization and binding to glycosaminoglycans (GAGs) are required for their function in cell recruitment. Interactions with GAGs facilitate the formation of gradients, which provide directional cues migrating cells. In contrast, is thought contribute affinity GAG interactions by providing a more extensive surface than single subunits alone. However, importance has not been extensively quantified. Additionally, ability chemokines form different oligomers suggested impart...
Leukocyte recruitment from the vasculature into tissues is a crucial component of immune system but also key to inflammatory disease. Chemokines are central this process have yet be therapeutically targeted during inflammation due lack mechanistic understanding. Specifically, CXCL4 (Platelet Factor 4, PF4) has no established receptor that explains its function. Here, we use biophysical, in vitro, and vivo techniques determine mechanism underlying CXCL4-mediated leukocyte recruitment. We...
The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many soluble signalling molecules such as chemokines growth factors, regulates their transport effector functions. It is, however, unknown whether upon binding HS these proteins can affect long-range structure HS. To test this idea, we interrogated a supramolecular model system, which chains grafted to streptavidin-functionalized oligoethylene glycol monolayers or...
Reciprocal N-terminal interactions sequester a chemokine at the atypical receptor ACKR3.
This study provides proof of concept for cell-based heparin without heparin-induced thrombocytopenia side effects.
Chemokine-driven leukocyte recruitment is a key component of the immune response and various diseases. Therapeutically targeting chemokine system in inflammatory disease has been unsuccessful, which attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies. analyzed expression genes encoding their receptors across species, tissues, This analysis revealed complex patterns such that mediated same type were...
Abstract Although human lung macrophages are heterogenous and play key roles during health disease, the mechanisms that govern their activation function unclear, particularly in type 2 settings. Our understanding of how respond to inflammatory signals have predominantly relied on cell lines or peripheral blood derived cells, which a limited capacity reflect complexity tissue macrophage responses. Therefore, we isolated from resected stimulated them ex vivo under (IL-4, IL-13, IL-4 + IL-13) 1...
Chemokines control the migration of cells in normal physiological processes and context disease such as inflammation, autoimmunity cancer. Two major interactions are involved: (i) binding chemokines to chemokine receptors, which activates cellular machinery required for movement; (ii) glycosaminoglycans (GAGs), facilitates organization into haptotactic gradients that direct cell movement. can bind activate their receptors monomers; however, ability oligomerize is critical function many vivo...
Inflammatory chemokines and their receptors are central to the development of inflammatory/immune pathologies. The apparent complexity this system, coupled with lack appropriate in vivo models, has limited our understanding how orchestrate inflammatory responses hampered attempts at targeting system disease. Novel approaches therefore needed provide crucial biological, therapeutic, insights into chemokine-chemokine receptor family. Here, we report generation transgenic multi-chemokine...
There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab NF2-associated VS demonstrates value therapies targeting microvascular microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target.To characterize relationship between growth, TAM infiltration, circulating monocyte chemokines a large cohort patients with VS.Immunostaining for Iba1 (macrophages), CD31...
Abstract CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites plays prominent roles in inflammatory pathologies cancer. It has therefore been highlighted as important therapeutic target. However the success targeting threatened by our relative lack knowledge its precise vivo mode action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated response cutaneous peritoneal stimuli. In both situations, this associated...
Abstract Microglia, resident brain immune cells, are critical in orchestrating responses to central nervous system (CNS) injury. Many microglial functions, such as phagocytosis, motility and chemotaxis, suggested rely on chloride channels, including the volume‐regulated anion channel (VRAC), but studies date have relied use of pharmacological tools with limited specificity. VRAC has also been proposed a drug target for acute CNS injury, its role function is considerable interest developing...
Introduction CXCL17 is a mucosally secreted protein, and the most recently identified human chemokine, an assignment based on protein fold prediction chemotactic activity for leukocytes. However, these credentials have been subject of much recent discussion no experimental evidence has presented regarding definitive structure CXCL17. In this study, we evaluated structural chemoattractant to better characterize molecule, gain deeper insights into its functional role as glycosaminoglycan (GAG)...
To elucidate the ligand-binding surface of CC chemokine-binding proteins Evasin-1 and Evasin-4, produced by tick Rhipicephalus sanguineus, we sought to identify key determinants responsible for their different chemokine selectivities expressing Evasin mutants using phage display. We first designed alanine based on Evasin-1·CCL3 complex structure an in silico model Evasin-4 bound CCL3. The were displayed M13 particles, binding was assessed ELISA. Selected variants then as purified...