scholarly journals Tetraspanins Associated With oxLDL and IgG Mediated Phagocytosis In Human U937 Macrophages

2021 ◽  
Author(s):  
Pardis Pakshir
Keyword(s):  
Cell Surface ◽  
Signaling Pathways ◽  
Laser Scanning ◽  
Laser Scanning Confocal Microscopy ◽  
Fc Receptor ◽  
Surface Proteins ◽  
Specific Cell ◽  
Cell Surface Proteins ◽  
Scanning Confocal Microscopy ◽  
Receptor Complexes

One of the crucial key targets in treatment of diseases are cell surface proteins, such as receptor complexes, and their associated signaling pathways. The Fc receptor is one of the most important phagocytic receptors of the cells of immune system. The ligand of the Fc gamma receptor is immunoglobulin G (IgG), which triggers the engulfment of foreign molecules coated by antibodies by a process called phagocytosis. A Specialized subset of cells including macrophages engulfs foreign particles by the Fc receptor. Another phagocytic receptor of macrophages is the CD36 receptor, which binds the ligand oxLDL and is known to be involved in the development of atherosclerotic lesions in the arteries. A few members of the Tetraspanin proteins have been found to be associated with theses receptors in macrophages. Tetraspanins may act as “molecular facilitators” grouping specific cell-surface proteins and thus increasing the formation and stability of functional signaling complexes. There is a significant amount of research done on the receptors of the surface of macrophages, however, the proteins associated with these receptors, their potential signaling pathways and the mechanisms involved are not yet fully understood. This thesis aims to investigate the presence and potential functional role of the specific Tetraspanin isoforms in Fc and CD36 mediated phagocytosis. Silencing RNA, quantitative assays of phagocytosis, and laser scanning confocal microscopy were used to test the phagocytic efficiency of macrophages in IgG and oxLDL mediated phagocytosis. Understanding the regulatory roles of Tetraspanins can provide insight into various immune diseases.

scholarly journals Tetraspanins Associated With oxLDL and IgG Mediated Phagocytosis In Human U937 Macrophages

2021 ◽  
Author(s):  
Pardis Pakshir
Keyword(s):  
Cell Surface ◽  
Signaling Pathways ◽  
Laser Scanning ◽  
Laser Scanning Confocal Microscopy ◽  
Fc Receptor ◽  
Surface Proteins ◽  
Specific Cell ◽  
Cell Surface Proteins ◽  
Scanning Confocal Microscopy ◽  
Receptor Complexes

One of the crucial key targets in treatment of diseases are cell surface proteins, such as receptor complexes, and their associated signaling pathways. The Fc receptor is one of the most important phagocytic receptors of the cells of immune system. The ligand of the Fc gamma receptor is immunoglobulin G (IgG), which triggers the engulfment of foreign molecules coated by antibodies by a process called phagocytosis. A Specialized subset of cells including macrophages engulfs foreign particles by the Fc receptor. Another phagocytic receptor of macrophages is the CD36 receptor, which binds the ligand oxLDL and is known to be involved in the development of atherosclerotic lesions in the arteries. A few members of the Tetraspanin proteins have been found to be associated with theses receptors in macrophages. Tetraspanins may act as “molecular facilitators” grouping specific cell-surface proteins and thus increasing the formation and stability of functional signaling complexes. There is a significant amount of research done on the receptors of the surface of macrophages, however, the proteins associated with these receptors, their potential signaling pathways and the mechanisms involved are not yet fully understood. This thesis aims to investigate the presence and potential functional role of the specific Tetraspanin isoforms in Fc and CD36 mediated phagocytosis. Silencing RNA, quantitative assays of phagocytosis, and laser scanning confocal microscopy were used to test the phagocytic efficiency of macrophages in IgG and oxLDL mediated phagocytosis. Understanding the regulatory roles of Tetraspanins can provide insight into various immune diseases.

scholarly journals The Diverse Contributions of Fucose Linkages in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1241 ◽  
Author(s):  
Tyler S. Keeley ◽  
Shengyu Yang ◽  
Eric Lau
Keyword(s):  
Cell Surface ◽  
Signaling Pathways ◽  
Cancer Biology ◽  
Surface Proteins ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Therapeutic Approaches ◽  
Cell Surface Proteins ◽  
Clinical Diagnostic

Fucosylation is a post-translational modification of glycans, proteins, and lipids that is responsible for many biological processes. Fucose conjugation via α(1,2), α(1,3), α(1,4), α(1,6), and O’- linkages to glycans, and variations in fucosylation linkages, has important implications for cancer biology. This review focuses on the roles that fucosylation plays in cancer, specifically through modulation of cell surface proteins and signaling pathways. How L-fucose and serum fucosylation patterns might be used for future clinical diagnostic, prognostic, and therapeutic approaches will be discussed.

scholarly journals FAK and PYK2 are specifically associated with the activated phagocytic receptor complexes from human U937 cells.

2021 ◽  
Author(s):  
Marwan G. AbidAlthagafi
Keyword(s):  
Cell Surface ◽  
Tyrosine Kinases ◽  
Laser Scanning ◽  
Surface Proteins ◽  
Protein Tyrosine Kinases ◽  
Macrophage Cell ◽  
Protein Tyrosine ◽  
Surface Receptors ◽  
Receptor Complexes

The innate immune system is the first shield against foreign attack inside the human body, and it is usually carried out with phagocytosis. An essential macrophage cell surface protein is the Fc receptor which contributes to the engulfment of unknown antigens. One of the important members of Fc receptors is the gamma receptor that binds to the immunoglobulin G (IgG) ligand. Another key receptor in this study is the CD36 receptor, which plays a crucial role in the progression of atherosclerosis, the hardening of arteries, with its ligand oxidized low-density lipoprotein (OxLDL). In this report, protein tyrosine kinase enzymes have been detected in the involvement of receptor complexes with human U937 macrophages, specifically PTK2 and PTK2b genes. Protein tyrosine kinases were known to promote cell migration as a main player in intracellular signal transduction cascades in relation to extracellular stimuli. Cell surface proteins are essential for the immunization of various diseases; yet, the molecular machinery of surface receptors remains unclear. This research primarily examined the dynamic nature of protein tyrosine kinases in an ongoing investigation of macrophage cell surface receptors, particularly the role of Fc γ and CD36 receptors with their ligands IgG and oxLDL coated beads in phagocytosis. Our report demonstrates a novel role of PTK2 and PTK2b functions in relation to U937 CD36-mediated phagocytosis. The Phagocytic efficiency of U937 macrophages was analyzed using laser scanning confocal microscope after silencing the cells with siRNA followed by quantitative counting of phagocytosis. The PF drug FAK inhibitor was also introduced to compare the phagocytic efficiency of siRNA cells.

Mechanism of antibody stimulation of hexose transport in rat myoblasts

1984 ◽  
Vol 62 (5) ◽  
pp. 255-265 ◽  
Author(s):  
Theodore C. Y. Lo ◽  
Vincent Duronio
Keyword(s):  
Cell Surface ◽  
Covalent Modification ◽  
Membrane Receptors ◽  
Surface Proteins ◽  
Specific Cell ◽  
Activation Process ◽  
Hexose Transport ◽  
Antibody Treatment ◽  
Cell Surface Proteins ◽  
Membrane Components

We have recently demonstrated that exposure of rat myoblasts to anti-rat myoblast antiserum results in two- to three-fold activation of hexose transport. The present communication reports the possible mechanism(s) by which specific antibody can bring about such activation. Studies with Fab and Fc fragments indicate that the binding of Fab to specific cell surface component(s) is not sufficient to trigger activation of hexose transport; the immunoglobulin G (IgG) mediated dimerization of membrane components is required for this process. Although cytochalasin D has no effect on hexose transport in control and antibody-treated cells, pretreatment of cells with this inhibitor prevents antibody-mediated activation of hexose transport. It may be inferred from this observation that proper disposition of membrane components is required for the dimerization of membrane receptors. Since this activation of hexose transport is an irreversible process, it is possible that covalent modification of membrane components may have occurred as a result of antibody treatment. Pretreatment of cells with ammonium chloride or methylamine is found to abolish the antibody-mediated activation of hexose transport, even though these inhibitors have no effect on hexose transport in control and antibody-treated cells. These inhibitors may be acting on transglutaminase and (or) on some other proteins involved in the activation process. Several lines of evidence suggest that limited proteolytic cleavage of membrane components may be involved in the antibody-mediated activation of hexose transport. First, pretreatment with several protease inhibitors prevents activation of hexose transport. Second, several cell surface proteins are missing in antibody-treated cells. Third, limited proteolysis of cell surface proteins with trypsin can also bring about activation of hexose transport. In view of the fact that proteolytic activity cannot be detected in various IgG and serum preparations, it seems likely that endogenous membrane associated proteases may be involved in this activation process.

scholarly journals A computational study of co-inhibitory immune complex assembly at the interface between T cells and antigen presenting cells

2021 ◽  
Vol 17 (3) ◽  
pp. e1008825
Author(s):  
Zhaoqian Su ◽  
Kalyani Dhusia ◽  
Yinghao Wu
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Cell Surface ◽  
Immune Complex ◽  
Surface Proteins ◽  
Cell Surface Proteins ◽  
Receptor Complexes ◽  
Inhibitory Signaling ◽  
Programed Cell Death ◽  
Antigen Presenting

The activation and differentiation of T-cells are mainly directly by their co-regulatory receptors. T lymphocyte-associated protein-4 (CTLA-4) and programed cell death-1 (PD-1) are two of the most important co-regulatory receptors. Binding of PD-1 and CTLA-4 with their corresponding ligands programed cell death-ligand 1 (PD-L1) and B7 on the antigen presenting cells (APC) activates two central co-inhibitory signaling pathways to suppress T cell functions. Interestingly, recent experiments have identified a new cis-interaction between PD-L1 and B7, suggesting that a crosstalk exists between two co-inhibitory receptors and the two pairs of ligand-receptor complexes can undergo dynamic oligomerization. Inspired by these experimental evidences, we developed a coarse-grained model to characterize the assembling of an immune complex consisting of CLTA-4, B7, PD-L1 and PD-1. These four proteins and their interactions form a small network motif. The temporal dynamics and spatial pattern formation of this network was simulated by a diffusion-reaction algorithm. Our simulation method incorporates the membrane confinement of cell surface proteins and geometric arrangement of different binding interfaces between these proteins. A wide range of binding constants was tested for the interactions involved in the network. Interestingly, we show that the CTLA-4/B7 ligand-receptor complexes can first form linear oligomers, while these oligomers further align together into two-dimensional clusters. Similar phenomenon has also been observed in other systems of cell surface proteins. Our test results further indicate that both co-inhibitory signaling pathways activated by B7 and PD-L1 can be down-regulated by the new cis-interaction between these two ligands, consistent with previous experimental evidences. Finally, the simulations also suggest that the dynamic and the spatial properties of the immune complex assembly are highly determined by the energetics of molecular interactions in the network. Our study, therefore, brings new insights to the co-regulatory mechanisms of T cell activation.

Host cell-surface proteins as substrates of gingipains, the main proteases of Porphyromonas gingivalis

2018 ◽  
Vol 399 (12) ◽  
pp. 1353-1361 ◽  
Author(s):  
Katarina Hočevar ◽  
Jan Potempa ◽  
Boris Turk
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Signaling Pathways ◽  
Porphyromonas Gingivalis ◽  
Cysteine Proteases ◽  
Surface Proteins ◽  
Published Data ◽  
Tissue Destruction ◽  
Cell Surface Proteins ◽  
Host Cell Surface

Abstract Gingipains are extracellular cysteine proteases of the oral pathogen Porphyromonas gingivalis and are its most potent virulence factors. They can degrade a great variety of host proteins, thereby helping the bacterium to evade the host immune response, deregulate signaling pathways, trigger anoikis and, finally, cause tissue destruction. Host cell-surface proteins targeted by gingipains are the main focus of this review and span three groups of substrates: immune-regulatory proteins, signaling pathways regulators and adhesion molecules. The analysis of published data revealed that gingipains predominantly inactivate their substrates by cleaving them at one or more sites, or through complete degradation. Sometimes, gingipains were even found to initially shed their membrane substrates, but this was mostly just the first step in the degradation of cell-surface proteins.

Generation of a Platform for Identification of CLL Specific Cell Surface Proteins Targeted by Anti-Tumor Antibodies in Patient Sera After Allogeneic Hematopoietic Cell Transplantion

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1349-1349
Author(s):  
Brian C Shaffer ◽  
Judith Leitner ◽  
Adrian Wiestner ◽  
Michael R. Bishop ◽  
Steven Z. Pavletic ◽  
...  
Keyword(s):  
Cell Surface ◽  
Conflicts Of Interest ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Surface Proteins ◽  
Unrelated Donor ◽  
Specific Cell ◽  
Serum Antibodies ◽  
Cell Surface Proteins ◽  
Specific Cell Surface

Abstract Abstract 1349 Background: Clinical and translational studies suggest that allogeneic hematopoietic cell transplantation (alloHCT) may induce production of anti-tumor antibodies in the recipient after transplantation. We hypothesized that this phenomenon can serve as a platform for the generation of novel therapeutic monoclonal antibodies (mAbs). An important step to this goal is the identification of targeted antigens with defined ability to support antibody induced cell death. To address this challenge, we developed a chronic lymphocytic leukemia (CLL) membrane protein display system capable of discovering cell surface proteins targeted by serum antibodies and applied this tool to post-alloHCT patient samples. Methods: Total and mRNA was purified from peripheral blood mononuclear cells from six untreated CLL patients and used to generate cDNA. The patient cDNA was pooled, cloned into the retroviral vector pBMN, and expressed in the murine T-cell line Bw 5147 (Bw-CLL-Lib). Enrichment of Bw-CLL-Lib cells displaying membrane proteins of interest was performed via fluorescence activated cell sorting. The unselected Bw-CLL-Lib pool was blocked with recombinant human Fc followed by staining with 1:200 diluted post-alloHCT patient sera and by secondary staining with pooled Alexa Fluor 647 labeled goat-anti-human-lambda and -anti-kappa light chain specific antibodies. Bw-CLL-Lib cells positively binding to serum antibodies were collected and re-grown in culture to 1×106 cells. A second round of enrichment was performed, after which the Bw-CLL-Lib cells were placed in limiting dilution culture. Individual clones were screened for serum reactivity and the retroviral inserts in reactive Bw-CLL-Lib clones were rescued via PCR and sequenced. Proteins of interest were re-expressed in Bw 5147 cells and used to confirm reactivity of the patient serum with specific cell surface proteins. Results: The Bw-CLL-Lib cell pool was screened separately with serum from ten patients with CLL post unrelated donor alloHCT. Serum from three patients enriched positively binding Bw-CLL-Lib clones. Thus far, we have successfully identified serum antibodies to a membrane proximal epitope on a therapeutically relevant CLL cell surface protein. Conclusions: Here we demonstrate a methodology for identifying targets of anti-tumor antibodies in serum from patients after alloHCT. This technique yields a high degree of successful identification of antibody reactivity with cell surface proteins in post alloHCT serum samples. When combined with post-alloHCT antibody Fab phage display (Baskar et al., Blood 114, 4494–4502, 2009) this methodology forms a complete drug and target discovery platform for the generation of tumor specific mAbs derived from alloHCT patients. Disclosures: No relevant conflicts of interest to declare.

Laser Scanning Confocal Microscopic Analysis of Cells Transfected with Genes of Varicella Zoster Virus

1997 ◽  
Vol 3 (S2) ◽  
pp. 91-92
Author(s):  
Charles Grose ◽  
Christopher Hatfield ◽  
Julie Olson ◽  
Chantee Buranathai
Keyword(s):  
Confocal Microscopy ◽  
Cell Surface ◽  
Varicella Zoster Virus ◽  
Laser Scanning ◽  
Microscopic Analysis ◽  
Laser Scanning Confocal Microscopy ◽  
Coated Vesicle ◽  
Varicella Zoster ◽  
Surface Receptors ◽  
Scanning Confocal Microscopy

Varicella-zoster virus (VZV) is one of the human herpes viruses. It causes chickenpox in childhood; after chickenpox the virus remains in a latent state in the dorsal root ganglia of the spinal cord. When the virus reactivates in late adulthood, it causes the disease known as shingles or herpes zoster. The VZV genome includes approximately 70 open-reading frames, but only a few of the gene products have been well characterized.The VZV glycoproteins include gH, gL, gE and gI. The gH:gL complex is an important viral fusogen. Through laser scanning confocal microscopy, we developed an assay to measure VZV-induced fusion and syncytial formation. VZV also encodes a cell surface Fc receptor, glycoprotein gE. VZV gE has previously been shown to display several features common to nonviral cell surface receptors. Attention focused on the ability of VZV gE to undergo receptor-mediated endocytosis. The transient transfection studies demonstrated by confocal microscopy and intemalization assays that VZV gE was endocytosed when expressed in HeLa cells. Endocytosis of gE was shown to be dependent on clathrin-coated vesicle formation within the cells.

scholarly journals Society Medal and Awards Winners for 2006

2005 ◽  
Vol 27 (4) ◽  
pp. 57-60
Keyword(s):  
Cell Surface ◽  
B Lymphocytes ◽  
Cell Types ◽  
Surface Antigens ◽  
Surface Proteins ◽  
Specific Cell ◽  
Cell Surface Antigens ◽  
Cell Surface Proteins ◽  
Extracellular Signals ◽  
Proliferation And Differentiation

Congratulations go to the following scientists who will be recipients of the Society's Awards in 2006. use antibodies against cell-surface antigens to distinguish and separate T- and B-lymphocytes and to show that antibody binding causes a redistribution and endocytosis of cell-surface proteins. He has studied the intracellular programmes and extracellular signals that control the survival, growth, proliferation and differentiation of specific cell types of the developing rodent nervous system.

scholarly journals Glycosylphosphatidylinositol-Anchored Cell Surface Proteins Regulate Position-Specific Cell Affinity in the Limb Bud

1998 ◽  
Vol 202 (2) ◽  
pp. 244-252 ◽  
Author(s):  
Naoyuki Wada ◽  
Ichiro Kimura ◽  
Hideaki Tanaka ◽  
Hiroyuki Ide ◽  
Tsutomu Nohno
Keyword(s):  
Cell Surface ◽  
Surface Proteins ◽  
Limb Bud ◽  
Specific Cell ◽  
Cell Surface Proteins ◽  
Cell Affinity
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