Neutrophil granulocytes: adhesion and locomotion on collagen substrata and in collagen matrices

1982 ◽  
Vol 58 (1) ◽  
pp. 455-467
Author(s):  
A.F. Brown
Keyword(s):  
Hyaluronic Acid ◽  
Chondroitin Sulphate ◽  
Three Dimensional ◽  
Neutrophil Granulocytes ◽  
Variable Properties ◽  
Collagen Fibres ◽  
Collagen Matrices ◽  
Coated Glass

Neutrophil granulocytes (PMNs) adhere poorly to and are unable to locomote on collagen-coated glass; they are able to attach to and invade three-dimensional matrices of collagen fibres. Invasion is largely independent of adhesion to the fibres, does not occur by proteolysis of the gel, and is not affected by the presence of fibronectin or chondroitin sulphate. Invasion is reduced by increasing the concentration of collagen in the gel or by the presence of hyaluronic acid. It is proposed that in both these situations there is physical obstruction of PMN movement. The ability to locomote through tissues of very variable properties in vivo is important in the role of the PMN in inflammation.

Crystal structure of the FAS1 domain of the hyaluronic acid receptor stabilin-2

2018 ◽  
Vol 74 (7) ◽  
pp. 695-701 ◽  
Author(s):  
Aleksandra Twarda-Clapa ◽  
Beata Labuzek ◽  
Dobroslawa Krzemien ◽  
Bogdan Musielak ◽  
Przemyslaw Grudnik ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Cancer Metastasis ◽  
Potential Role ◽  
Three Dimensional ◽  
Protein Fragments ◽  
Acid Receptor ◽  
X Ray ◽  
Insight Into

Recent research has identified a potential role of the hyaluronic acid receptor stabilin-2 (Stab2) in cancer metastasis. Stab2 belongs to a group of scavenger receptors and is responsible for the clearance of more than ten ligands, including hyaluronic acid (HA). In vivo experiments on mice have shown that the absence of Stab2, or its blocking by an antibody, effectively opposes cancer metastasis, which is accompanied by an increase in the level of circulating HA. Knowledge of ligand recognition and signal transduction by Stab2 is limited and no three-dimensional structures of any protein fragments of this receptor have been solved to date. Here, a high-resolution X-ray structure of the seventh FAS1 domain of Stab2 is reported. This structure provides the first insight into the Stab2 structure.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals The Role of Pre-Clinical 3-Dimensional Models of Osteosarcoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5499
Author(s):  
Hannah L. Smith ◽  
Stephen A. Beers ◽  
Juliet C. Gray ◽  
Janos M. Kanczler
Keyword(s):  
Three Dimensional ◽  
Chorioallantoic Membrane ◽  
3D Models ◽  
In Ovo ◽  
Future Directions ◽  
3 Dimensional ◽  
In Vivo Animal Models

Treatment for osteosarcoma (OS) has been largely unchanged for several decades, with typical therapies being a mixture of chemotherapy and surgery. Although therapeutic targets and products against cancer are being continually developed, only a limited number have proved therapeutically active in OS. Thus, the understanding of the OS microenvironment and its interactions are becoming more important in developing new therapies. Three-dimensional (3D) models are important tools in increasing our understanding of complex mechanisms and interactions, such as in OS. In this review, in vivo animal models, in vitro 3D models and in ovo chorioallantoic membrane (CAM) models, are evaluated and discussed as to their contribution in understanding the progressive nature of OS, and cancer research. We aim to provide insight and prospective future directions into the potential translation of 3D models in OS.

The extracellular matrix of the developing cornea: diversity, deposition and function*

Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 195-205
Author(s):  
J. B. L. Bard ◽  
M. K. Bansal ◽  
A. S. A. Ross
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulphate ◽  
Corneal Stroma ◽  
Experimental System ◽  
Collagen I ◽  
And Function ◽  
20 Nm

This paper examines the role of the extracellular matrix (ECM) in the development of the cornea. After a brief summary of the corneal structure and ECM, we describe evidence suggesting that the differentiation of neural crest (NC) cells into endothelium and fibroblasts is under the control of ocular ECM. We then examine the role of collagen I in stromal morphogenesis by comparing normal corneas with those of homozygous Movl3 mice which do not make collagen I. We report that, in spite of this absence, the cellular morphology of the Movl3 eye is indistinguishable from that of the wild type. In the 16-day mutant stroma, however, the remaining collagens form small amounts of disorganized, thin fibrils rather than orthogonally organized 20 nm-diameter fibrils; a result implying that collagen I plays only a structural role and that its absence is not compensated for. It also suggests that, because these remaining collagens will not form the normal fibrils that they will in vitro, fibrillogenesis in the corneal stroma differs from that elsewhere. The latter part of the paper describes our current work on chick stromal deposition using corneal epithelia isolated with an intact basal lamina that lay down in vitro ∼3μm-thick stromas of organized fibrils similar to that seen in vivo. This experimental system has yielded two unexpected results. First, the amount of collagen and proteoglycans produced by such epithelia is not dependent on whether its substratum is collagenous and we therefore conclude that stromal production by the intact epithelium is more autonomous than hitherto thought. Second, chondroitin sulphate (CS), the predominant proteoglycan, appears to play no role in stromal morphogenesis: epithelia cultured in testicular hyaluronidase, which degrades CS, lay down stromas whose organization and fibrildiameter distribution are indistinguishable from controls. One possible role for CS, however, is as a lubricant which facilitates corneal growth: it could allow fibrils to move over one another without deforming their orthogonal organization. Finally, we have examined the processes of fibrillogenesis in the corneal stroma and conclude that they are different from those elsewhere in the embryo and in vitro, perhaps because there is in the primary stroma an unidentified, highly hydrated ECM macromolecule that embeds the fibrils and that may mediate their morphogenesis.

Association between tension and orientation of periodontal ligament fibroblasts and exogenous collagen fibres in collagen gels in vitro

1982 ◽  
Vol 58 (1) ◽  
pp. 125-138
Author(s):  
C.G. Bellows ◽  
A.H. Melcher ◽  
J.E. Aubin
Keyword(s):  
Three Dimensional ◽  
Lower Surface ◽  
Cytochalasin D ◽  
Collagen Gels ◽  
Collagen Fibres ◽  
Periodontal Ligament Fibroblasts ◽  
The Relationship ◽  
Develop Tension

The relationship between the development of tension in sheets of fibroblasts and the orientation of these cells and collagen fibres in collagen gels was examined. Cell-containing, three-dimensional collagen gels were established in agarose-coated Epon dies measuring 10 mm X 4 mm X 4 mm, to which pieces of demineralized tooth and bone had been attached at opposite ends. Contraction of the gel into an opaque structure suspended between the two particles occurred over 24 h and resulted in concave upper and lateral surfaces and a flat to slightly concave lower surface. Initial orientation of the fibres along the tooth-bone axis was followed by similar orientation of the cells. Gels cast without cells exhibited no change in dimensions. Release of the tooth particle after 12 or 24 h of incubation led to shortening of the contracted gels 5 min following release. This shortening was significantly greater (P less than 0.001) than that of uncontracted or slightly contracted gels (1 h and 3 h incubation). Gels attached at one end only compacted around the site of attachment but did not show orientation of cells or fibres. Gels containing colcemid or cytochalasin D were only slightly compacted and did not develop tension. Collagen fibres, but not cell in colcemid-containing gels, showed some alignment; neither were aligned in the presence of cytochalasin D. These data suggest that both microtubules and microfilaments are necessary for alignment of cells and the establishment of tension between two points of attachment in collagen gels. Furthermore, they lend support to our previously advanced hypothesis that the development of tension between two points can result in the orientation of the cells along an axis connecting the points of attachment. This could provide a mechanism for the development of oriented fibre systems in vivo.

Role of macrophage CD44 in the disposal of inflammatory cell corpses*

2002 ◽  
Vol 103 (5) ◽  
pp. 441-449 ◽  
Author(s):  
Sharon VIVERS ◽  
Ian DRANSFIELD ◽  
Simon P. HART
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Surrounding Tissue ◽  
Human Macrophage ◽  
Neutrophil Granulocytes ◽  
Apoptotic Cells ◽  
Tissue Destruction

Understanding the cellular and molecular mechanisms that determine whether inflammation resolves or progresses to scarring and tissue destruction should lead to the development of effective therapeutic strategies for inflammatory diseases. Apoptosis of neutrophil granulocytes is an important determinant of the resolution of inflammation, providing a mechanism for down-regulation of function and triggering clearance by macrophages without inducing a pro-inflammatory response. However, if the rate of cell death by apoptosis is such that the macrophage clearance capacity is exceeded, apoptotic cells may progress to secondary necrosis, resulting in the release of harmful cellular contents and in damage to the surrounding tissue. There are many possible ways in which the rate and capacity of the macrophage-mediated clearance of apoptotic cells may be enhanced or suppressed. Ligation of human macrophage surface CD44 by bivalent monoclonal antibodies rapidly and profoundly augments the capacity of macrophages to phagocytose apoptotic neutrophils in vitro. The molecular mechanism behind this effect and its potential significance in vivo is a current focus of research.

Local, Three-Dimensional Strain Measurements Within Largely Deformed Extracellular Matrix Constructs

2004 ◽  
Vol 126 (6) ◽  
pp. 699-708 ◽  
Author(s):  
Blayne A. Roeder ◽  
Klod Kokini ◽  
J. Paul Robinson ◽  
Sherry L. Voytik-Harbin
Keyword(s):  
Extracellular Matrix ◽  
Local Level ◽  
Three Dimensional ◽  
Collagen Matrices ◽  
Mechanical Loads ◽  
Strain Measurements ◽  
3D Collagen ◽  
Vitro Model

The ability to create extracellular matrix (ECM) constructs that are mechanically and biochemically similar to those found in vivo and to understand how their properties affect cellular responses will drive the next generation of tissue engineering strategies. To date, many mechanisms by which cells biochemically communicate with the ECM are known. However, the mechanisms by which mechanical information is transmitted between cells and their ECM remain to be elucidated. “Self-assembled” collagen matrices provide an in vitro-model system to study the mechanical behavior of ECM. To begin to understand how the ECM and the cells interact mechanically, the three-dimensional (3D) mechanical properties of the ECM must be quantified at the micro-(local) level in addition to information measured at the macro-(global) level. Here we describe an incremental digital volume correlation (IDVC) algorithm to quantify large (>0.05) 3D mechanical strains in the microstructure of 3D collagen matrices in response to applied mechanical loads. Strain measurements from the IDVC algorithm rely on 3D confocal images acquired from collagen matrices under applied mechanical loads. The accuracy and the precision of the IDVC algorithm was verified by comparing both image volumes collected in succession when no deformation was applied to the ECM (zero strain) and image volumes to which simulated deformations were applied in both 1D and 3D (simulated strains). Results indicate that the IDVC algorithm can accurately and precisely determine the 3D strain state inside largely deformed collagen ECMs. Finally, the usefulness of the algorithm was demonstrated by measuring the microlevel 3D strain response of a collagen ECM loaded in tension.

scholarly journals Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens

2019 ◽  
Author(s):  
Sara Pedron ◽  
Gabrielle L. Wolter ◽  
Jee-Wei E. Chen ◽  
Sarah E. Laken ◽  
Jann N. Sarkaria ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Tumor Microenvironment ◽  
Kinase Inhibitor ◽  
Egfr Mutations ◽  
Primary Glioblastoma ◽  
Stat3 Phosphorylation

AbstractTherapeutic options to treat primary glioblastoma (GBM) tumors are scarce. GBM tumors with epidermal growth factor receptor (EGFR) mutations, in particular a constitutively active EGFRvIII mutant, have extremely poor clinical outcomes. GBM tumors with concurrent EGFR amplification and active phosphatase and tensin homolog (PTEN) are sensitive to the tyrosine kinase inhibitor erlotinib, but the effect is not durable. A persistent challenge to improved treatment is the poorly understood role of cellular, metabolic, and biophysical signals from the GBM tumor microenvironment on therapeutic efficacy and acquired resistance. The intractable nature of studying GBM cell in vivo motivates tissue engineering approaches to replicate aspects of the complex GBM tumor microenvironment. Here, we profile the effect of erlotinib on two patient-derived GBM specimens: EGFR+ GBM12 and EGFRvIII GBM6. We use a three-dimensional gelatin hydrogel to present brain-mimetic hyaluronic acid (HA) and evaluate the coordinated influence of extracellular matrix signals and EGFR mutation status on GBM cell migration, survival and proliferation, as well as signaling pathway activation in response to cyclic erlotinib exposure. Comparable to results observed in vivo for xenograft tumors, erlotinib exposure is not cytotoxic for GBM6 EGFRvIII specimens. We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBM EGFR+ cells by modifying STAT3 phosphorylation status. Taken together, we report an in vitro tissue engineered platform to monitor signaling associated with poor response to targeted inhibitors in GBM.

The crosstalk of hyaluronan-based extracellular matrix and synapses

2008 ◽  
Vol 4 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Renato Frischknecht ◽  
Constanze I. Seidenbecher
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Hyaluronic Acid ◽  
Chondroitin Sulphate ◽  
Specific Form ◽  
Perineuronal Net ◽  
Chondroitin Sulphate Proteoglycans ◽  
And Function ◽  
Brain Extracellular Space

Many neurons and their synapses are enwrapped in a brain-specific form of the extracellular matrix (ECM), the so-called perineuronal net (PNN). It forms late in the postnatal development around the time when synaptic contacts are stabilized. It is made of glycoproteins and proteoglycans of glial as well as neuronal origin. The major organizing polysaccharide of brain extracellular space is the polymeric carbohydrate hyaluronic acid (HA). It forms the backbone of a meshwork consisting of CNS proteoglycans such as the lectican family of chondroitin sulphate proteoglycans (CSPG). This family comprises four abundant components of brain ECM: aggrecan and versican as broadly expressed CSPGs and neurocan and brevican as nervous-system-specific family members. In this review, we intend to focus on the specific role of the HA-based ECM in synapse development and function.

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