Perspectives on the Biological Role of Chemokine:Glycosaminoglycan Interactions

Handel, Tracy M.; Dyer, Douglas P.

doi:10.1369/0022155420977971

Cited by 22 publications

(36 citation statements)

References 51 publications

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“…Whilst speculative in the context here, this type of formational change is feasible, for example by selective binding mechanisms to the actin cytoskeleton ( Yoneda and Couchman, 2003 ; Multhaupt et al, 2009 ; Li and Wang, 2019 ), and would allow for great functional control over what is a dynamic system. Further, there would still be direct GAG control over the filtration via other mechanisms, such as those hypothesized in immunology for clumping of the HS leaving short term gaps ( Dyer et al, 2017 ; Handel and Dyer, 2021 ) as well as the activity of shedases [e.g., ( Annecke et al, 2011 )].…”

Section: Resultsmentioning

confidence: 99%

A Reinterpretation of Evidence for the Endothelial Glycocalyx Filtration Structure

Arkill

2021

Front. Cell Dev. Biol.

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The endothelial glycocalyx (eGlx) is thought to be the primary macromolecular filter for fluid flux out of the vasculature. This filter maintains the higher protein concentration within the vessel lumen relative to the tissue. Whilst the arguments for the eGlx being the size filter are convincing the structural evidence has been limited to specialized stains of perfusion fixed tissue, which are further processed for resin embedding for transmission electron microscopy. The staining and processing of the delicate pore structure has left many researchers struggling to interpret the observed surface coat. Previous work has alluded to a 19.5 nm spacing between fibers; however, whilst repeatable it does not give an eGlx pore size consistent with known glycosaminoglycan (GAG) molecular structure due to the required fiber thickness of >10 nm. Here a new interpretation is proposed based on the likelihood that the electron micrographs of are often of collapsed eGlx. The 19.5 nm spacing measured may therefore be the core protein of the proteoglycans (PGs) with the GAGs wrapped up around them rather than in an expanded in vivo state. The concept is explored to determine that this is indeed consistent with experimental measurements of permeability if the syndecans are predominately dimerized. Further an alteration of core protein lattice from hexagonal packing to square packing dramatically changes the permeability which could be facilitated via known mechanisms such as transient actin binding.

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Section: Resultsmentioning

confidence: 99%

A Reinterpretation of Evidence for the Endothelial Glycocalyx Filtration Structure

Arkill

2021

Front. Cell Dev. Biol.

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“…17 Versican can also provide indirect, fine control over leukocyte migration into the lungs through interactions of the negatively charged chondroitin sulfate chains on versican with chemokines. [27][28][29]64,65 Previous studies demonstrate that versican interacts with chemokine CCL2, creating a gradient that promotes monocyte migration 17 and that globally versican-deficient animals exposed to poly(I: C) had reduced expression of chemokine CXCL2, a potent neutrophil chemoattractant. 66 Mice with epithelialspecific versican deficiency demonstrated increased recruitment of monocytes and neutrophils in BAL fluid and elevated expression levels of chemokines CCL2, CCL3, and CCL4 after infection with the respiratory syncytial virus, suggesting that epithelial versican attenuates leukocyte migration through chemokine-mediated mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…12,16,17,[23][24][25][26] Versican also retains, releases, and interacts with cytokines, chemokines, and growth factors, which further inform immune cell activity and direct the host inflammatory response. [27][28][29] Two signaling pathways, previously identified in vitro in specific cellular lineages, are responsible for versican expression. In smooth muscle cells, the canonical Wnt/β-catenin/Tcell factor (TCF) pathway controls versican promoter activity, and β-catenin signaling is required for transforming growth factor-β1-induced versican expression.…”

Section: Introductionmentioning

confidence: 99%

Type I Interferon Signaling Increases Versican Expression and Synthesis in Lung Stromal Cells During Influenza Infection

Brune

Chang

Altemeier

et al. 2021

J Histochem Cytochem.

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Versican, a chondroitin sulfate proteoglycan, is an essential component of the extracellular matrix (ECM) in inflammatory lung disease. Versican’s potential as an immunomodulatory molecule makes it a promising therapeutic target for controlling host immune responses in the lungs. To establish changes to versican expression and accumulation during influenza A viral pneumonia, we document the temporal and spatial changes to versican mRNA and protein in concert with pulmonary inflammatory cell infiltration. These studies were performed in the lungs of wild-type C57BL6/J mice on days 3, 6, 9, and 12 post-infection with influenza A virus using immunohistochemistry, in situ hybridization, and quantitative digital pathology. Using duplex in situ hybridization, we demonstrate that type I interferon signaling contributes significantly to versican expression in lung stromal cells. Our findings show that versican is a type I interferon–stimulated gene in pulmonary fibroblasts and pericytes in the context of viral pneumonia. These data also provide a guide for future studies to determine the role of versican in the pulmonary immune response to influenza infection:

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“…Such a lectin interaction could also have the advantage of being specific for a cell type, depending on the glycosylation status of the cell [ 20 ]. Furthermore, signaling by TFF2 could also be more complex, e.g., by binding to glycosaminoglycans, as shown for a number of cytokines [ 163 ].…”

Section: Role Of Tff Peptides For Inflammatory Processesmentioning

confidence: 99%

Trefoil Factor Family (TFF) Peptides and Their Links to Inflammation: A Re-evaluation and New Medical Perspectives

Hoffmann

2021

IJMS

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Trefoil factor family peptides (TFF1, TFF2, TFF3), together with mucins, are typical exocrine products of mucous epithelia. Here, they act as a gastric tumor suppressor (TFF1) or they play different roles in mucosal innate immune defense (TFF2, TFF3). Minute amounts are also secreted as endocrine, e.g., by the immune and central nervous systems. As a hallmark, TFF peptides have different lectin activities, best characterized for TFF2, but also TFF1. Pathologically, ectopic expression occurs during inflammation and in various tumors. In this review, the role of TFF peptides during inflammation is discussed on two levels. On the one hand, the expression of TFF1-3 is regulated by inflammatory signals in different ways (upstream links). On the other hand, TFF peptides influence inflammatory processes (downstream links). The latter are recognized best in various Tff-deficient mice, which have completely different phenotypes. In particular, TFF2 is secreted by myeloid cells (e.g., macrophages) and lymphocytes (e.g., memory T cells), where it modulates immune reactions triggering inflammation. As a new concept, in addition to lectin-triggered activation, a hypothetical lectin-triggered inhibition of glycosylated transmembrane receptors by TFF peptides is discussed. Thus, TFFs are promising players in the field of glycoimmunology, such as galectins and C-type lectins.

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Perspectives on the Biological Role of Chemokine:Glycosaminoglycan Interactions

Cited by 22 publications

References 51 publications

A Reinterpretation of Evidence for the Endothelial Glycocalyx Filtration Structure

A Reinterpretation of Evidence for the Endothelial Glycocalyx Filtration Structure

Type I Interferon Signaling Increases Versican Expression and Synthesis in Lung Stromal Cells During Influenza Infection

Trefoil Factor Family (TFF) Peptides and Their Links to Inflammation: A Re-evaluation and New Medical Perspectives

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