Cellular Adhesion in Inflammation

2014 ◽  
pp. 83-97
Author(s):  
David H. Broide ◽  
P. Sriramarao
Keyword(s):  
Author(s):  
S.L. Erlandsen

Cells interact with their extracellular environments by means of a variety of cellular adhesion molecules (CAM) and surface ligands. In many instances, CAMs interact in a sequential temporal fashion which suggests that these adhesion molecules may occupy or be polarized to various membrane microdomains on the cell surface. Detection of CAMs can be accomplished by a variety of methods including immunofluorescent microscopy and flow cytometry, and by the use of immunocytochemical markers (i.e. colloidal gold) in electron microscopy. The development of high resolution field emission SEM in the mid 1980's and the Autrata modification of the YAG detector for backscatter electron detection at low voltage has greatly facilitated the recognition of colloidal gold probes for detection of surface CAMs. Low voltage FESEM with Bse imaging provides increased resolution of cell surface topography (~3nm at 3-4 keV) which can be observed in 3-dimensions, and simultaneously permits detection/high spatial resolution of immunogold label by atomic number contrast.


2018 ◽  
Vol 2 (3) ◽  
pp. 184-201
Author(s):  
George D Glinos ◽  
Irena Pastar ◽  
Marjana Tomic-Canic ◽  
Rivka C Stone

Darier disease (DD) is an autosomal dominant keratinizing genodermatosis that manifests clinically with red-brown pruritic papules in a seborrheic distribution often in association with palmoplantar pits and dystrophic nail changes. It is caused by mutation in ATP2A2 which encodes a sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2) pump that regulates calcium flux. Consequent alteration of intracellular calcium homeostasis is thought to impair trafficking of cellular adhesion proteins and to lead to aberrant keratinocyte differentiation, contributing to the characteristic histopathologic features of acantholysis and dyskeratosis in DD, though the precise mechanisms are incompletely understood. Previous studies have identified defective localization of desmosomal attachment proteins in skin biopsies and cultured keratinocytes from DD patients, but reports of effects on adherens junction proteins (including calcium-dependent E-cadherin) are conflicting. Here we describe a case of DD presenting with characteristic clinical and histologic features in which we performed immunofluorescence staining of four adherens junction-associated proteins (E-cadherin, α-catenin, β-catenin, and vinculin). In lesional (acantholytic) DD skin, we identified loss of distinctive bright membranous staining that was present at the periphery of keratinocytes throughout the epidermis in the healthy skin of a matched donor. Perilesional (non-acantholytic) portions of DD skin partially recapitulated the normal phenotype. Our findings support a role for SERCA2 dysfunction in impaired assembly of adherens junctions, which together with defective desmosomes contribute to acantholysis in DD.


Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2104
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe

The management of chronic wounds is challenging. The factors that impede wound healing include malnutrition, diseases (such as diabetes, cancer), and bacterial infection. Most of the presently utilized wound dressing materials suffer from severe limitations, including poor antibacterial and mechanical properties. Wound dressings formulated from the combination of biopolymers and synthetic polymers (i.e., poly (vinyl alcohol) or poly (ε-caprolactone) display interesting properties, including good biocompatibility, improved biodegradation, good mechanical properties and antimicrobial effects, promote tissue regeneration, etc. Formulation of these wound dressings via electrospinning technique is cost-effective, useful for uniform and continuous nanofibers with controllable pore structure, high porosity, excellent swelling capacity, good gaseous exchange, excellent cellular adhesion, and show a good capability to provide moisture and warmth environment for the accelerated wound healing process. Based on the above-mentioned outstanding properties of nanofibers and the unique properties of hybrid wound dressings prepared from poly (vinyl alcohol) and poly (ε-caprolactone), this review reports the in vitro and in vivo outcomes of the reported hybrid nanofibers.


2021 ◽  
Vol 22 (14) ◽  
pp. 7362
Author(s):  
Amina Ben Abla ◽  
Guilhem Boeuf ◽  
Ahmed Elmarjou ◽  
Cyrine Dridi ◽  
Florence Poirier ◽  
...  

Engineering of biomimetic motives have emerged as promising approaches to improving cells’ binding properties of biomaterials for tissue engineering and regenerative medicine. In this study, a bio-adhesive ligand including cell-binding domains of human fibronectin (FN) was engineered using recombinant protein technology, a major extracellular matrix (ECM) protein that interacts with a variety of integrins cell-surface’s receptors and other ECM proteins through specific binding domains. 9th and 10th fibronectin type III repeat containing Arginine-Glycine-Aspartic acid (RGD) and Pro-His-Ser-Arg-Asn (PHSRN) synergic site (FNIII9-10) were expressed in fusion with a Colored Multi Affinity Tag (CMAT) to develop a simplified production and characterization process. A recombinant fragment was produced in the bacterial system using E. coli with high yield purified protein by double affinity chromatography. Bio-adhesive surfaces were developed by passive coating of produced fragment onto non adhesive surfaces model. The recombinant fusion protein (CMAT-FNIII9/10) demonstrated an accurate monitoring capability during expression purification and adsorption assay. Finally, biological activity of recombinant FNIII9/10 was validated by cellular adhesion assay. Binding to α5β1 integrins were successfully validated using a produced fragment as a ligand. These results are robust supports to the rational development of bioactivation strategies for biomedical and biotechnological applications.


2020 ◽  
Vol 02 (04) ◽  
pp. 342-357
Author(s):  
Francesco Zaccarian ◽  
Matthew B. Baker ◽  
Matthew J. Webber

Protein fouling can render a biomedical device dysfunctional, and also serves to nucleate the foreign body reaction to an implanted material. Hydrophilic coatings have emerged as a commonly applied route to combat interface-mediated complications and promote device longevity and limited inflammatory response. While polyethylene glycol has received a majority of the attention in this regard, coatings based on zwitterionic moieties have been more recently explored. Sulfobetaines in particular constitute one such class of zwitterions explored for use in mitigating surface fouling, and have been shown to reduce protein adsorption, limit cellular adhesion, and promote increased functional lifetimes and limited inflammatory responses when applied to implanted materials and devices. Here, we present a focused review of the literature surrounding sulfobetaine, beginning with an understanding of its chemistry and the methods by which it is applied to the surface of a biomedical device in molecular and polymeric forms, and then advancing to the many early demonstrations of function in a variety of biomedical applications. Finally, we provide some insights into the benefits and challenges presented by its use, as well as some outlook on the future prospects for using this material to improve biomedical device practice by addressing interface-mediated complications.


Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 380
Author(s):  
Nikolaos Vrachnis ◽  
Dimitrios Zygouris ◽  
Dionysios Vrachnis ◽  
Nikolaos Roussos ◽  
Nikolaos Loukas ◽  
...  

In spite of the great advances made in recent years in prenatal and perinatal medicine, inflammation can still frequently result in injury to vital organs and often constitutes a major cause of morbidity. It is today well established that in neonates—though vulnerability to infection among neonates is triggered by functional impairments in leukocyte adhesion—the decreased expression of cell adhesion molecules also decreases the inflammatory response. It is also clear that the cell adhesion molecules, namely, the integrins, selectins, and the immunoglobulin (Ig) gene super family, all play a crucial role in the inflammatory cascade. Thus, by consolidating our knowledge concerning the actions of these vital cell adhesion molecules during the prenatal period as well as regarding the genetic deficiencies of these molecules, notably leukocyte adhesion deficiency (LAD) I, II, and III, which can provoke severe clinical symptoms throughout the first year of life, it is anticipated that intervention involving blocking the function of cell adhesion molecules in neonatal leukocytes has the potential to constitute an effective therapeutic approach for inflammation. A promising perspective is the potential use of antibody therapy in preterm and term infants with perinatal inflammation and infection focusing on cases in which LAD is involved, while a further important scientific advance related to this issue could be the combination of small peptides aimed at the inhibition of cellular adhesion.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Song ◽  
Oladapo O. Yeku ◽  
Sarwish Rafiq ◽  
Terence Purdon ◽  
Xue Dong ◽  
...  

AbstractImmunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic β-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness.


2001 ◽  
Vol 86 (07) ◽  
pp. 164-171 ◽  
Author(s):  
Thalia Romani de Wit ◽  
Jan van Mourik

SummaryVon Willebrand factor (VWF) is a multifunctional plasma protein that plays a prominent role in haemostasis. In endothelial cells, processing of its precursor pro-VWF results in the formation of two large polypeptides, mature VWF and a propeptide. These proteins are co-secreted on an equimolar basis but are cleared from the circulation at different rates. VWF levels are frequently elevated in response to vascular disorders. Similarly, propeptide levels are increased under these conditions, although primarily in fulminant vascular disease, such as thrombotic thrombocytopenic purpura and septicemia. In chronic vascular disease, e.g. diabetes or peripheral vascular disease, propeptide levels are much less elevated. The differential response of VWF and propeptide levels to vascular disease could provide a means to assess the extent and time course of endothelial cell activation. After secretion, the propeptide may play a role in modulating cellular adhesion processes. Thus, enhanced propeptide secretion seems not to be of merely diagnostic significance.


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