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Sample records for adhesion molecule ncam

  1. The Neural Cell Adhesion Molecule NCAM2/OCAM/RNCAM, a Close Relative to NCAM

    Kulahin, Nikolaj; Walmod, Peter

    2008-01-01

    molecule (NCAM) is a well characterized, ubiquitously expressed CAM that is highly expressed in the nervous system. In addition to mediating cell adhesion, NCAM participates in a multitude of cellular events, including survival, migration, and differentiation of cells, outgrowth of neurites, and formation......Cell adhesion molecules (CAMs) constitute a large class of plasma membrane-anchored proteins that mediate attachment between neighboring cells and between cells and the surrounding extracellular matrix (ECM). However, CAMs are more than simple mediators of cell adhesion. The neural cell adhesion...... and plasticity of synapses. NCAM shares an overall sequence identity of approximately 44% with the neural cell adhesion molecule 2 (NCAM2), a protein also known as olfactory cell adhesion molecule (OCAM) and Rb-8 neural cell adhesion molecule (RNCAM), and the region-for-region sequence homology...

  2. Neural cell adhesion molecule (NCAM) and prealbumin in cerebrospinal fluid from depressed patients

    Jørgensen, Ole Steen

    1988-01-01

    The size of the soluble form of the human cerebrospinal fluid (CSF) neural cell adhesion molecule, NCAM-sol, was by gel permeation chromatography estimated to 160-250 kDa. Within the CSF the concentration of NCAM-sol was found about 15-25% increased in lumbar fluid and 25% increased in ventricular...

  3. Transfection of glioma cells with the neural-cell adhesion molecule NCAM

    Edvardsen, K; Pedersen, P H; Bjerkvig, R; Hermann, G G; Zeuthen, J; Laerum, O D; Walsh, F S; Bock, E

    1994-01-01

    The tumor growth and the invasive capacity of a rat glioma cell line (BT4Cn) were studied after transfection with the human transmembrane 140-kDa isoform of the neural-cell adhesion molecule, NCAM. After s.c. injection, the NCAM-transfected cells showed a slower growth rate than the parent cell...... line (BT4Cn). Upon intracerebral implantation with BT4Cn cells and different clones of NCAM-transfected cells, all animals developed neurological symptoms within 13-16 days. However, the tumors showed different growth characteristics. The NCAM-transfected BT4Cn cells were localized in the region of the...

  4. The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

    Zecchini, Silvia; Bombardelli, Lorenzo; Decio, Alessandra; Bianchi, Marco; Mazzarol, Giovanni; Sanguineti, Fabio; Aletti, Giovanni; Maddaluno, Luigi; Berezin, Vladimir; Bock, Elisabeth; Casadio, Chiara; Viale, Giuseppe; Colombo, Nicoletta; Giavazzi, Raffaella; Cavallaro, Ugo

    2011-01-01

    Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surfa...

  5. Neural cell adhesion molecule (N-CAM) domains and intracellular signaling pathways involved in the inhibition of astrocyte proliferation

    Krushel, Leslie A.; Tai, Ming-Hong; Cunningham, Bruce A.; Edelman, Gerald M.; Crossin, Kathryn L.

    1998-01-01

    The neural cell adhesion molecule (N-CAM) inhibits astrocyte proliferation in vitro and in vivo, and this effect is partially reversed by the glucocorticoid antagonist RU-486. The present studies have tested the hypothesis that N-CAM-mediated inhibition of astrocyte proliferation is caused by homophilic binding and involves the activation of glucocorticoid receptors. It was observed that all N-CAM Ig domains inhibited astrocyte proliferation in parallel with their ability to influence N-CAM b...

  6. Transmembrane neural cell-adhesion molecule (NCAM), but not glycosyl-phosphatidylinositol-anchored NCAM, down-regulates secretion of matrix metalloproteinases

    Edvardsen, K; Chen, W; Rucklidge, G;

    1993-01-01

    proteinases, and proteinase inhibitors all participate in the construction, maintenance, and remodeling of extracellular matrix by cells. The neural cell-adhesion molecule (NCAM)-negative rat glioma cell line BT4Cn secretes substantial amounts of metalloproteinases, as compared with its NCAM-positive mother......During embryogenesis interactions between cells and extracellular matrix play a central role in the modulation of cell motility, growth, and differentiation. Modulation of matrix structure is therefore crucial during development; extracellular matrix ligands, their receptors, extracellular...... cell line BT4C. We have transfected the BT4Cn cell line with cDNAs encoding the human NCAM-B and -C isoforms. We report here that the expression of transmembrane NCAM-B, but not of glycosyl-phosphatidylinositol-linked NCAM-C, induces a down-regulation of 92-kDa gelatinase (matrix metalloproteinase 9...

  7. Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning

    Køhler, Lene B; Christensen, Claus; Rossetti, Clara; Fantin, Martina; Sandi, Carmen; Bock, Elisabeth; Berezin, Vladimir

    2010-01-01

    Neural cell adhesion molecule (NCAM)-mediated cell adhesion results in activation of intracellular signaling cascades that lead to cellular responses such as neurite outgrowth, neuronal survival, and modulation of synaptic activity associated with cognitive processes. The crystal structure of the...... between Ig1 and Ig3 and between Ig2 and Ig2, respectively, observed in the crystal structure. Although the two dennexin peptides differed in amino acid sequence, they both modulated cell adhesion, reflected by inhibition of NCAM-mediated neurite outgrowth. Both dennexins also promoted neuronal survival...... immunoglobulin (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM homophilic adhesion. The present study addressed the biological significance of the so called dense zipper formation of NCAM. Two peptides, termed dennexinA and dennexinB, were modeled after the contact interfaces...

  8. Signaling mechanisms of neurite outgrowth induced by the cell adhesion molecules NCAM and N-cadherin

    Hansen, S M; Berezin, V; Bock, E

    2008-01-01

    Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact with the...... extracellular guidance cues to intracellular events and thereby regulating neurite outgrowth. In this review, we focus on two CAMs, the neural cell adhesion molecule (NCAM) and N-cadherin, and their ability to mediate signaling associated with a neurite outgrowth response. In particular, we will focus on direct...... surroundings via the extracellular domain and bind to the cytoskeleton via their intracellular domain. In addition, several CAMs induce signaling events via direct interactions with intracellular proteins or via interactions with cell surface receptors. Thus, CAMs are obvious candidates for transmitting...

  9. Extracellular Protein Interactions Mediated by the Neural Cell Adhesion Molecule, NCAM: Heterophilic Interactions Between NCAM and Cell Adhesion Molecules, Extracellular Matrix Proteins, and Viruses

    Nielsen, Janne; Kulahin, Nikolaj; Walmod, Peter

    2008-01-01

    interactions, thereby modulating a range of biological processes. This review summarizes interactions between NCAM and other CAMs and ECM proteins. Additionally, the role of NCAM as a receptor for rabies virus, and its implications in rabies infections is briefly described. Interactions between NCAM and its...

  10. Structural basis of cell-cell adhesion by NCAM

    Kasper, C; Rasmussen, H; Kastrup, Jette Sandholm Jensen; Ikemizu, S; Jones, E Y; Berezin, V; Bock, E; Larsen, I K

    2000-01-01

    The neural cell adhesion molecule NCAM, a member of the immunoglobulin superfamily, mediates cell-cell recognition and adhesion via a homophilic interaction. NCAM plays a key role during development and regeneration of the nervous system and is involved in synaptic plasticity associated with memory...

  11. Polysialic Acid Neural Cell Adhesion Molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines

    Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure. Although patient survival is limited to one year on average, significant variability in outcome is observed. The assessment of biomarkers is needed to gain better knowledge of this type of tumor, help prognosis, design and evaluate therapies. The neurodevelopmental polysialic acid neural cell adhesion molecule (PSA-NCAM) protein is overexpressed in various cancers. Here, we studied its expression in GBM and evaluated its prognosis value for overall survival (OS) and disease free survival (DFS). We set up a specific and sensitive enzyme linked immunosorbent assay (ELISA) test for PSA-NCAM quantification, which correlated well with PSA-NCAM semi quantitative analysis by immunohistochemistry, and thus provides an accurate quantitative measurement of PSA-NCAM content for the 56 GBM biopsies analyzed. For statistics, the Spearman correlation coefficient was used to evaluate the consistency between the immunohistochemistry and ELISA data. Patients' survival was estimated by using the Kaplan-Meier method, and curves were compared using the log-rank test. On multivariate analysis, the effect of potential risk factors on the DFS and OS were evaluated using the cox regression proportional hazard models. The threshold for statistical significance was p = 0.05. We showed that PSA-NCAM was expressed by approximately two thirds of the GBM at variable levels. On univariate analysis, PSA-NCAM content was an adverse prognosis factor for both OS (p = 0.04) and DFS (p = 0.0017). On multivariate analysis, PSA-NCAM expression was an independent negative predictor of OS (p = 0.046) and DFS (p = 0.007). Furthermore, in glioma cell lines, PSA-NCAM level expression was correlated to the one of olig2, a transcription factor required for gliomagenesis. PSA-NCAM represents a valuable biomarker for the prognosis of GBM patients

  12. Age-related changes in expression of neural cell adhesion molecule (NCAM) in heart

    1993-01-01

    ). Alternative splicing of NCAM mRNA was analyzed by Northern blotting using DNA oligonucleotide probes designed for demonstration of certain exons or exon combinations. Total NCAM mRNA was downregulated during postnatal development followed by upregulation in the aging heart. Three major NCAM mRNA classes of 6.......7, 5.2 and 2.9 kb were expressed in newborn heart in approximately equal proportions. At all other ages, the mRNAs of 5.2 and 2.9 kb were more predominant than the 6.7 kb mRNA. During postnatal development and aging, expression of exon VASE was selectively downregulated in the 6.7 kb NCAM mRNA class......, whereas it was clearly detectable in NCAM mRNA classes of 5.2 and 2.9 kb. Insertion of exons a and AAG between exons 12 and 13 was more pronounced in the 5.2 and 2.9 kb NCAM mRNAs than in the 6.7 kb mRNA at all ages. Insertions at the 12/13 junctions decreased in the 6.7 kb mRNA as compared to the 5.2 and...

  13. New serum markers for small-cell lung cancer. II. The neural cell adhesion molecule, NCAM

    Vangsted, A; Drivsholm, L; Andersen, E;

    1994-01-01

    concentration was found between SCLC patients with localized and extensive disease. Serum from one patient with cancer of the thyroid, but no sera from non-SCLC patients or normal healthy controls, was positive. The expression of NCAM did not correlate to any of the clinical parameters, and no correlation was...

  14. Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL

    Aonurm-Helm, Anu; Jurgenson, Monika; Zharkovsky, Tamara; Sonn, Katrin; Berezin, Vladimir; Bock, Elisabeth; Zharkovsky, Alexander

    2008-01-01

    in the sucrose preference test, reduced adult neurogenesis in the dentate gyrus and reduced levels of the phosphorylated cAMP response element-binding protein (pCREB) in the hippocampus. FGL administered acutely or repeatedly reduced depression-like behaviour in NCAM(-/-) mice without having an...

  15. Neural cell adhesion molecule induces intracellular signaling via multiple mechanisms of Ca2+ homeostasis

    Kiryushko, Darya; Korshunova, Irina; Berezin, Vladimir; Bock, Elisabeth

    2006-01-01

    The neural cell adhesion molecule (NCAM) plays a pivotal role in the development of the nervous system, promoting neuronal differentiation via homophilic (NCAM-NCAM) as well as heterophilic (NCAM-fibroblast growth factor receptor [FGFR]) interactions. NCAM-induced intracellular signaling has been...

  16. Evidence for heterophilic adhesion of embryonic retinal cells and neuroblastoma cells to substratum-adsorbed NCAM

    1992-01-01

    The adhesion of embryonic chicken retinal cells and mouse N2A neuroblastoma cells to purified embryonic chicken retinal NCAM adsorbed on a solid substratum was examined using a quantitative centrifugal adhesion assay. Both cell types adhered to NCAM and the adhesion was specifically inhibited by monovalent anti-NCAM antibody fragments. N2A cell adhesion depended on the amount of NCAM applied to the substratum, was cation independent, and was insensitive to treatment with the cytoskeletal pert...

  17. NCAM regulates cell motility

    Prag, Søren; Lepekhin, Eugene A; Kolkova, Kateryna;

    2002-01-01

    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells...... independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a...... fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine...

  18. The neural cell adhesion molecule

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  19. NCAM2/OCAM/RNCAM

    Winther, Malene; Berezin, Vladimir; Walmod, Peter Schledermann

    2012-01-01

    Neural cell adhesion molecules 2 (NCAM2/OCAM/RNCAM), is a paralog of NCAM1. The protein exists in a transmembrane and a lipid-anchored isoform, and has an ectodomain consisting of five immunoglobulin modules and two fibronectin type 3 homology modules. Structural models of the NCAM2 ectodomain re...

  20. Neural cell adhesion molecule-180-mediated homophilic binding induces epidermal growth factor receptor (EGFR) down-regulation and uncouples the inhibitory function of EGFR in neurite outgrowth

    Povlsen, Gro Klitgaard; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    The neural cell adhesion molecule (NCAM) plays important roles in neuronal development, regeneration, and synaptic plasticity. NCAM homophilic binding mediates cell adhesion and induces intracellular signals, in which the fibroblast growth factor receptor plays a prominent role. Recent studies on...... this NCAM-180-induced EGFR down-regulation involves increased EGFR ubiquitination and lysosomal EGFR degradation. Furthermore, NCAM-180-mediated EGFR down-regulation requires NCAM homophilic binding and interactions of the cytoplasmic domain of NCAM-180 with intracellular interaction partners, but does...

  1. Expression and function of neural cell adhesion molecule during limb regeneration.

    Maier, C E; Watanabe, M.(Niigata University, 950-2181, Niigata, Japan); Singer, M.; McQuarrie, I G; Sunshine, J.; Rutishauser, U.

    1986-01-01

    The neural cell adhesion molecule (NCAM) has been detected in regenerating limb bud of adult newts in addition to brain and peripheral nerves. In the regenerating tissue, NCAM was found primarily on mesenchymal cells and also in wound epidermis. Infusion of Fab fragments of antibodies to NCAM into limb buds at the early blastema stage delayed the regenerative process. Previous studies have indicated that NCAM serves as a homophilic ligand for adhesion among cells that express this molecule an...

  2. Effects of spaceflight in the adductor longus muscle of rats flown in the Soviet Biosatellite COSMOS 2044. A study employing neural cell adhesion molecule (N-CAM) immunocytochemistry and conventional morphological techniques (light and electron microscopy)

    D'Amelio, F.; Daunton, N. G.

    1992-01-01

    The effects of spaceflight upon the "slow" muscle adductor longus were examined in rats flown in the Soviet Biosatellite COSMOS 2044. The techniques employed included standard methods for light microscopy, neural cell adhesion molecule (N-CAM) immunocytochemistry and electron microscopy. Light microscopic observations revealed myofiber atrophy and segmental necrosis accompanied by cellular infiltrates composed of macrophages, leukocytes and mononuclear cells. Neural cell adhesion molecule immunoreactivity (N-CAM-IR) was seen on the myofiber surface and in regenerating myofibers. Ultrastructural alterations included Z band streaming, disorganization of myofibrillar architecture, sarcoplasmic degradation, extensive segmental necrosis with apparent preservation of the basement membrane, degenerative phenomena of the capillary endothelium and cellular invasion of necrotic areas. Regenerating myofibers were identified by the presence of increased amounts of ribosomal aggregates and chains of polyribosomes associated with myofilaments. The principal electron microscopic changes of the neuromuscular junctions showed axon terminals with a decrease or absence of synaptic vesicles replaced by microtubules and neurofilaments, degeneration of axon terminals, vacant axonal spaces and changes suggestive of axonal sprouting. The present observations suggest that alterations such as myofibrillar disruption and necrosis, muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight.

  3. Neural cell adhesion molecule differentially interacts with isoforms of the fibroblast growth factor receptor

    Christensen, Claus; Berezin, Vladimir; Bock, Elisabeth

    2011-01-01

    The fibroblast growth factor receptor (FGFR) can be activated through direct interactions with various fibroblast growth factors or through a number of cell adhesion molecules, including the neural cell adhesion molecule (NCAM). We produced recombinant proteins comprising the ligand...... the expression pattern of various FGFR isoforms determines the cell context-specific effects of NCAM signaling through FGFR....

  4. Triple Effect of Mimetic Peptides Interfering with Neural Cell Adhesion Molecule Homophilic Cis Interactions

    Li, S. Z.; Kolkova, Kateryna; Rudenko, Olga;

    2005-01-01

    and P2 acted as conventional antagonists, agonists, and reverse agonists of NCAM at low, intermediate, and high peptide concentrations, respectively. The demonstrated in vitro triple pharmacological effect of mimetic peptides interfering with the NCAM homophilic cis binding will be valuable for the......The neural cell adhesion molecule (NCAM) is pivotal in neural development, regeneration, and learning. Here we characterize two peptides, termed P1-B and P2, derived from the homophilic binding sites in the first two N-terminal immunoglobulin (Ig) modules of NCAM, with regard to their effects on...... neurite extension and adhesion. To evaluate how interference of these mimetic peptides with NCAM homophilic interactions in cis influences NCAM binding in trans, we employed a coculture system in which PC12-E2 cells were grown on monolayers of fibroblasts with or without NCAM expression and the rate of...

  5. Effect of NCAM-transfection on growth and invasion of a human cancer cell line

    Edvardsen, K; Bock, E; Jirus, S;

    1997-01-01

    A cDNA encoding the human transmembrane 140 kDa isoform of the neural cell adhesion molecule (NCAM) was transfected into the highly invasive MDA-MB-231 human breast cancer cell line. Transfectants with a homogeneous expression of NCAM showed a restricted capacity for penetration of an artificial ...... of the NCAM-transfected cells. The fact that NCAM expression influences growth regulation attributes a pivotal role to this cell adhesion molecule during ontogenesis and tumor development....

  6. Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle

    1993-01-01

    Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here...... virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2.......9 kb were present in perinatal and young adult skeletal muscle, whereas only the 5.2 and 2.9 kb mRNA classes could be demonstrated in aged muscle. This indicates that metabolism of the various NCAM polypeptides is individually regulated during aging. Alternative splicing of NCAM mRNA in skeletal muscle...

  7. The neural cell adhesion molecule binds to fibroblast growth factor receptor 2

    Christensen, Claus; Lauridsen, Jes B; Berezin, Vladimir; Bock, Elisabeth; Kiselyov, Vladislav V

    2006-01-01

    The neural cell adhesion molecule (NCAM) can bind to and activate fibroblast growth factor receptor 1 (FGFR1). However, there are four major FGFR isoforms (FGFR1-FGFR4), and it is not known whether NCAM also interacts directly with the other three FGFR isoforms. In this study, we show by surface...

  8. Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C

    Nybroe, O; Albrechtsen, M; Dahlin, J; Linnemann, D; Lyles, J M; Møller, C J; Bock, E

    1985-01-01

    The biosynthesis of the neural cell adhesion molecule (N-CAM) was studied in primary cultures of rat cerebral glial cells, cerebellar granule neurons, and skeletal muscle cells. The three cell types produced different N-CAM polypeptide patterns. Glial cells synthesized a 135,000 Mr polypeptide B...

  9. Neuritogenic and survival-promoting effects of the P2 peptide derived from a homophilic binding site in the neural cell adhesion molecule

    Pedersen, Martin V; Køhler, Lene B; Ditlevsen, Dorte K;

    2004-01-01

    The neural cell adhesion molecule (NCAM) plays a pivotal role in neural development, regeneration, and plasticity. NCAM mediates adhesion and subsequent signal transduction through NCAM-NCAM binding. Recently, a peptide ligand termed P2 corresponding to a 12-amino-acid sequence in the FG loop of...... fragmentation were lowered by P2. Finally, treatment of neurons with P2 resulted in phosphorylation of the ser/thr kinase Akt. Thus, a small peptide mimicking homophilic NCAM interaction is capable of inducing differentiation as reflected by neurite outgrowth in several neuronal cell types and inhibiting...

  10. Distinctive PSA-NCAM and NCAM Hallmarks in Glutamate-Induced Dendritic Atrophy and Synaptic Disassembly

    Podestá, María Fernanda; Yam, Patricia; Codagnone, Martín Gabriel; Uccelli, Nonthué Alejandra; Colman, David; Reinés, Analía

    2014-01-01

    Dendritic and synapse remodeling are forms of structural plasticity that play a critical role in normal hippocampal function. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) participate in neurite outgrowth and synapse formation and plasticity. However, it remains unclear whether they contribute to dendritic retraction and synaptic disassembly. Cultured hippocampal neurons exposed to glutamate (5 µM) showed a reduced MAP-2 (+) area in the absence of neuronal death 24 h after the insult. Concomitantly, synapse loss, revealed by decreased synaptophysin and post-synaptic density-95 cluster number and area, together with changes in NCAM and PSA-NCAM levels were found. Dendritic atrophy and PSA-NCAM reduction proved NMDA-receptor dependent. Live-imaging experiments evidenced dendritic atrophy 4 h after the insult; this effect was preceded by smaller NCAM clusters (1 h) and decreased surface and total PSA-NCAM levels (3 h). Simultaneously, total NCAM cluster number and area remained unchanged. The subsequent synapse disassembly (6 h) was accompanied by reductions in total NCAM cluster number and area. A PSA mimetic peptide prevented both the dendritic atrophy and the subsequent synaptic changes (6 h) but had no effect on the earliest synaptic remodeling (3 h). Thus, NCAM-synaptic reorganization and PSA-NCAM level decrease precede glutamate-induced dendritic atrophy, whereas the NCAM level reduction is a delayed event related to synapse loss. Consequently, distinctive stages in PSA-NCAM/NCAM balance seem to accompany glutamate-induced dendritic atrophy and synapse loss. PMID:25279838

  11. Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas

    Møller, C J; Christgau, S; Williamson, M R; Madsen, O D; Niu, Z P; Bock, E; Baekkeskov, S

    1992-01-01

    a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor...

  12. Synthetic NCAM-derived Ligands of the Fibroblast Growth Factor Receptor

    Hansen, Stine; Li, Shizhong; Bock, Elisabeth;

    2008-01-01

    The neural cell adhesion molecule (NCAM) responds to cues in the external environment and transmits signals to the cell through extracellular and intracellular interactions with a number of other signal transduction molecules. One such NCAM interaction partner is the fibroblast growth factor...... receptor (FGFR). NCAM interacts with FGFR via two fibronectin type III (FN3) modules in the extracellular part of NCAM. These modules consist of beta-strands and connecting loop regions. Based on structural analysis of the NCAM FN3 modules, four peptide sequences, FGL, BCL, dekaCAM, and FRM, encompassing...

  13. Modulation of the homophilic interaction between the first and second Ig modules of neural cell adhesion molecule by heparin

    Kulahin, Nikolaj; Rudenko, Olga; Kiselyov, V.;

    2005-01-01

    The second Ig module (IgII) of the neural cell adhesion molecule (NCAM) is known to bind to the first Ig module (IgI) of NCAM (so-called homophilic binding) and to interact with heparan sulfate and chondroitin sulfate glycoconjugates. We here show by NMR that the heparin and chondroitin sulfate......II. Accordingly, we show that treatment of cerebellar granule neurons (CGNs) with heparin inhibits NCAM-mediated outgrowth. In contrast, treatment with heparinase III or chondroitinase ABC abrogates NCAM-mediated neurite outgrowth in CGNs emphasizing the importance of the presence of heparan/chondroitin sulfates...

  14. Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells

    Andersson, A M; Moran, N; Gaardsvoll, H; Linnemann, D; Bjerkvig, R; Laerum, O D; Bock, Elisabeth Marianne

    1991-01-01

    The neural cell adhesion molecule, NCAM, plays an important role in cell-cell adhesion. Therefore, we have studied NCAM expression in the glioma cell lines BT4C and BT4Cn. We demonstrate that the 2 cell lines differ in their metastatic ability; while BT4C cells have a very low capacity for......-substratum binding assay in which the binding of BT4C and BT4Cn cells to NCAM immobilized to glass was assessed. We found thatBT4C cells adhere specifically to NCAM, and that adhesion is inhibited by anti-NCAM Fab'-fragments, while no specific binding of BT4Cn cells to NCAM was observed. The BT4C and BT4Cn cell...... lines thus constitute an important new model system for the study of tumor invasion and metastasis and of the role of cell adhesion molecules in these processes....

  15. Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle: a comparative study of newborn, adult and aged rats

    Andersson, A M; Olsen, M; Zhernosekov, D;

    1993-01-01

    Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here...... virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2.......9 kb were present in perinatal and young adult skeletal muscle, whereas only the 5.2 and 2.9 kb mRNA classes could be demonstrated in aged muscle. This indicates that metabolism of the various NCAM polypeptides is individually regulated during aging. Alternative splicing of NCAM mRNA in skeletal muscle...

  16. The neural cell adhesion molecule-derived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner

    Cox, F F; Berezin, V; Bock, E;

    2013-01-01

    Fibroblast growth loop (FGL) is a neural cell adhesion molecule (NCAM)-mimetic peptide that mimics the interaction of NCAM with fibroblast growth factor receptor (FGFR). FGL increases neurite outgrowth and promotes neuronal survival in vitro, and it has also been shown to have neuroprotective eff...

  17. NCAM Mimetic Peptides: An Update

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    pharmacological tools interfering with NCAM functions. Recent progress in our understanding of the structural basis of NCAM-mediated cell adhesion and signaling has allowed a structure-based design of NCAM mimetic peptides. Using this approach a number of peptides termed P2, P1-B, P-3-DE and P-3-G, whose...... sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling a number of peptides derived from NCAM and targeting NCAM heterophilic ligands such as the fibroblast growth factor receptor and...... heparan sulfate proteoglycans (HSPG) have been identified. The FGL, dekaCAM, FRM/EncaminA, BCL, EncaminC and EncaminE peptides all target the FGF receptor whereas the heparin binding peptide HBP targets HSPG. Moreover, a number of NCAM binding peptides have been identified employing screening of...

  18. A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial learning and neural plasticity in the hippocampus

    Kraev, Igor; Henneberger, Christian; Rossetti, Clara; Conboy, Lisa; Kohler, Lene B; Fantin, Martina; Jennings, Alistair; Venero, Cesar; Popov, Victor; Rusakov, Dmitri; Stewart, Michael G; Bock, Elisabeth; Berezin, Vladimir; Sandi, Carmen

    2011-01-01

    The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of ...

  19. Are NCAM deficient mice an animal model for schizophrenia?

    Anne eAlbrecht; Oliver eStork

    2012-01-01

    Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM) and its associated polysialic acid (PSA) as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we...

  20. Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

    Andersson, A M; Gaardsvoll, H; Giladi, E; Dahl, B; Bock, Elisabeth Marianne

    1990-01-01

    A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... oligonucleotides, that hybridize to different exons in the NCAM gene. Furthermore we have constructed three oligonucleotides, that exclusively hybridize to mRNAs lacking certain exons, by letting them consist of sequences adjacent to both sides of the splice sites. By means of these probes we have characterized...

  1. Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway

    Kolkova, K; Novitskaya, V; Pedersen, N;

    2000-01-01

    ), protein kinase C (PKC), and the Ras-mitogen-activated protein (MAP) kinase pathway. This was done using a coculture system consisting of PC12-E2 cells grown on fibroblasts, with or without NCAM expression, allowing NCAM-NCAM interactions resulting in neurite outgrowth. PC12-E2 cells were transiently......The signal transduction pathways associated with neural cell adhesion molecule (NCAM)-induced neuritogenesis are only partially characterized. We here demonstrate that NCAM-induced neurite outgrowth depends on activation of p59(fyn), focal adhesion kinase (FAK), phospholipase Cgamma (PLCgamma...... transfected with expression plasmids encoding constitutively active forms of Ras, Raf, MAP kinase kinases MEK1 and 2, dominant negative forms of Ras and Raf, and the FAK-related nonkinase. Alternatively, PC12-E2 cells were submitted to treatment with antibodies to the fibroblast growth factor (FGF) receptor...

  2. Effect of Batroxobin on Expression of Neural Cell Adhesion Molecule in Temporal Infarction Rats and Spatial Learning and Memory Disorder

    2001-01-01

    The effect of Batroxobin expression of neural cell adhesion molecule (NCAM) in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemical methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats and at the same time NCAM expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of NCAM immune reactive cells of Batroxobin-treated rats was more than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats and the regulation of the expression of NCAM is probably related to the neuroprotective mechanism.

  3. Are NCAM deficient mice an animal model for schizophrenia?

    Anne eAlbrecht

    2012-07-01

    Full Text Available Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM and its associated polysialic acid as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we studied social interaction and attention of NCAM null mutant (NCAM-/- mice as further hallmarks of schizophrenia. Nest building, which is generally associated with social behavior in rodents, was severely impaired, as NCAM-/- mice continuously collected smaller amounts of nest building material than their wild type littermates and built nests of poorer quality. However, social approach tested in a three- compartment- box was not affected and latent inhibition of Pavlovian fear memory was not disturbed in NCAM-/- mice. Although NCAM deficient mice do not display a typical schizophrenia-like phenotype, they may be useful for studying specific endophenotypes with relevance to the disease.

  4. Reciprocal interactions between cell adhesion molecules of the immunoglobulin superfamily and the cytoskeleton in neurons

    Vladimir eSytnyk

    2016-02-01

    Full Text Available Cell adhesion molecules of the immunoglobulin superfamily (IgSF including the neural cell adhesion molecule (NCAM and members of the L1 family of neuronal cell adhesion molecules play important functions in the developing nervous system by regulating formation, growth and branching of neurites and establishment of the synaptic contacts between neurons. In the mature brain, members of IgSF regulate synapse composition, function and plasticity required for learning and memory. The intracellular domains of IgSF cell adhesion molecules interact with the components of the cytoskeleton including the submembrane actin-spectrin meshwork, actin microfilaments, and microtubules. In this review, we summarize current data indicating that interactions between IgSF cell adhesion molecules and the cytoskeleton are reciprocal, and that while IgSF cell adhesion molecules regulate the assembly of the cytoskeleton, the cytoskeleton plays an important role in regulation of the functions of IgSF cell adhesion molecules. Reciprocal interactions between NCAM and L1 family members and the cytoskeleton and their role in neuronal differentiation and synapse formation are discussed in detail.

  5. Reciprocal Interactions between Cell Adhesion Molecules of the Immunoglobulin Superfamily and the Cytoskeleton in Neurons.

    Leshchyns'ka, Iryna; Sytnyk, Vladimir

    2016-01-01

    Cell adhesion molecules of the immunoglobulin superfamily (IgSF) including the neural cell adhesion molecule (NCAM) and members of the L1 family of neuronal cell adhesion molecules play important functions in the developing nervous system by regulating formation, growth and branching of neurites, and establishment of the synaptic contacts between neurons. In the mature brain, members of IgSF regulate synapse composition, function, and plasticity required for learning and memory. The intracellular domains of IgSF cell adhesion molecules interact with the components of the cytoskeleton including the submembrane actin-spectrin meshwork, actin microfilaments, and microtubules. In this review, we summarize current data indicating that interactions between IgSF cell adhesion molecules and the cytoskeleton are reciprocal, and that while IgSF cell adhesion molecules regulate the assembly of the cytoskeleton, the cytoskeleton plays an important role in regulation of the functions of IgSF cell adhesion molecules. Reciprocal interactions between NCAM and L1 family members and the cytoskeleton and their role in neuronal differentiation and synapse formation are discussed in detail. PMID:26909348

  6. Absence of polysialylated NCAM is an unfavorable prognostic phenotype for advanced stage neuroblastoma

    Isola Jorma

    2009-02-01

    Full Text Available Abstract Background The expression of a neural crest stem cell marker, polysialic acid (polySia, and its main carrier, neural cell adhesion molecule (NCAM, have been detected in some malignant tumors with high metastatic activity and unfavorable prognosis, but the diagnostic and prognostic value of polySia-NCAM in neuroblastoma is unclear. Methods A tumor tissue microarray (TMA of 36 paraffin-embedded neuroblastoma samples was utilized to detect polySia-NCAM expression with a polySia-binding fluorescent fusion protein, and polySia-NCAM expression was compared with clinical stage, age, MYCN amplification status, histology (INPC, and proliferation index (PI. Results PolySia-NCAM-positive neuroblastoma patients had more often metastases at diagnosis, and polySia-NCAM expression associated with advanced disease (P = 0.047. Most interestingly, absence of polySia-NCAM-expressing tumor cells in TMA samples, however, was a strong unfavorable prognostic factor for overall survival in advanced disease (P = 0.0004, especially when MYCN was not amplified. PolySia-NCAM-expressing bone marrow metastases were easily detected in smears, aspirates and biopsies. Conclusion PolySia-NCAM appears to be a new clinically significant molecular marker in neuroblastoma, hopefully with additional value in neuroblastoma risk stratification.

  7. Absence of polysialylated NCAM is an unfavorable prognostic phenotype for advanced stage neuroblastoma

    The expression of a neural crest stem cell marker, polysialic acid (polySia), and its main carrier, neural cell adhesion molecule (NCAM), have been detected in some malignant tumors with high metastatic activity and unfavorable prognosis, but the diagnostic and prognostic value of polySia-NCAM in neuroblastoma is unclear. A tumor tissue microarray (TMA) of 36 paraffin-embedded neuroblastoma samples was utilized to detect polySia-NCAM expression with a polySia-binding fluorescent fusion protein, and polySia-NCAM expression was compared with clinical stage, age, MYCN amplification status, histology (INPC), and proliferation index (PI). PolySia-NCAM-positive neuroblastoma patients had more often metastases at diagnosis, and polySia-NCAM expression associated with advanced disease (P = 0.047). Most interestingly, absence of polySia-NCAM-expressing tumor cells in TMA samples, however, was a strong unfavorable prognostic factor for overall survival in advanced disease (P = 0.0004), especially when MYCN was not amplified. PolySia-NCAM-expressing bone marrow metastases were easily detected in smears, aspirates and biopsies. PolySia-NCAM appears to be a new clinically significant molecular marker in neuroblastoma, hopefully with additional value in neuroblastoma risk stratification

  8. Age-Related Cognitive Impairments in Mice with a Conditional Ablation of the Neural Cell Adhesion Molecule

    Bisaz, Reto; Boadas-Vaello, Pere; Genoux, David; Sandi, Carmen

    2013-01-01

    Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However,…

  9. The effects of morphine treatment on the NCAM and its signaling in the MLDS of rats.

    Cao, Jun Ping; Wang, Hong Jun; Li, Li; Zhang, Su Ming

    2016-10-01

    Prolonged exposure to opiates induces a constellation of neuroadaptations, especially in the mesolimbic dopamine system (MLDS), which leads to alteration in the function of motivational circuitry. The neural cell adhesion molecule (NCAM) mediates cell-cell interactions and plays an important role in processes associated with neural plasticity. Moreover, it has been shown that NCAM were related to risk of alcoholism in human populations. Here, coimmunoprecipitation and western blotting were used to investigate whether morphine treatment induced alteration of the expression of NCAM or its signaling level in MLDS. The rats receiving escalating dose of morphine treatment were divided into three groups: morphine 1d, 3d and 5d group, which were injected subcutaneously with morphine hydrochloride for 1 day, 3 days and 5 days, respectively. Twelve hours after the last injection, animals were sacrificed and the tissues of ventral tegmental area (VTA), prefrontal cortex (PFC) and nucleus accumbens (NAc) were punched out to examine the expression of NCAM or its signaling level. The results showed that morphine treatment had no significant effect on the expression of NCAM, but downregulated the phosphorylation of NCAM-associated focal adhesion kinase (FAK) in the VTA and PFC of rats. In the NAc of rats, however, the expression of NCAM and its signaling were not altered significantly by morphine treatment. These results indicated that the downregulation of NCAM signaling in the VTA and PFC might be involved in the formation of morphine addiction. PMID:26821693

  10. The NCAM-derived P2 peptide facilitates recovery of cognitive and motor function and ameliorates neuropathology following traumatic brain injury

    Klementiev, B; Novikova, T; Korshunova, Irina;

    2008-01-01

    The neural cell adhesion molecule (NCAM) plays a crucial role during development and regeneration of the nervous system, mediating neuronal differentiation, survival and plasticity. Moreover, NCAM regulates learning and memory. A peptide termed P2, corresponding to a 12-amino-acid sequence...

  11. Cyclic AMP regulates NCAM expression and phosphorylation in cultured mouse astrocytes

    Gegelashvili, George; Andersson, A M; Schousboe, Arne;

    1993-01-01

    The neural cell adhesion molecule (NCAM) plays a key morphoregulatory role during neural development. Patterns of NCAM expression were investigated in cultured astrocytes exhibiting distinct states of morphological differentiation. In vitro differentiation of confluent primary cultures of...... astrocytes was enhanced by a long-term (7 days) treatment with dibutyryl cyclic AMP (dBcAMP). The diversity of NCAM mRNAs arising from alternative splicing of a single primary transcript was analyzed by Northern blotting. Synthetic DNA-oligonucleotide probes, designed to recognize selected exons (exons 7, 15......, and VASE) or exon combinations (exons 7/8, exons 12/13, and exons 12/a/AAG/13), revealed NCAM mRNA classes of 6.7, 5.2, and 2.9 kilobases (kb) in both control and dBcAMP-treated astrocytes. Although long-term treatment of astrocytes with dBcAMP did not change the qualitative pattern of NCAM...

  12. Brain structure, cognition and negative symptoms in schizophrenia are associated with serum levels of polysialic acid-modified NCAM.

    Piras, F; Schiff, M; Chiapponi, C; Bossù, P; Mühlenhoff, M; Caltagirone, C; Gerardy-Schahn, R; Hildebrandt, H; Spalletta, G

    2015-01-01

    The neural cell adhesion molecule (NCAM) is a glycoprotein implicated in cell-cell adhesion, neurite outgrowth and synaptic plasticity. Polysialic acid (polySia) is mainly attached to NCAM (polySia-NCAM) and has an essential role in regulating NCAM-dependent developmental processes that require plasticity, that is, cell migration, axon guidance and synapse formation. Post-mortem and genetic evidence suggests that dysregulation of polySia-NCAM is involved in schizophrenia (SZ). We enrolled 45 patients diagnosed with SZ and 45 healthy individuals who were submitted to polySia-NCAM peripheral quantification, cognitive and psychopathological assessment and structural neuroimaging (brain volumes and diffusion tensor imaging). PolySia-NCAM serum levels were increased in SZ patients, independently of antipsychotic treatment, and were associated with negative symptoms, blunted affect and declarative memory impairment. The increased polySia-NCAM levels were associated with decreased volume in the left prefrontal cortex, namely Brodmann area 46, in patients and increased volume in the same brain area of healthy individuals. As this brain region is involved in the pathophysiology of SZ and its associated phenomenology, the data indicate that polySia-NCAM deserves further scrutiny because of its possible role in early neurodevelopmental mechanisms of the disorder. PMID:26460482

  13. Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain.

    Murray, Helen C; Low, Victoria F; Swanson, Molly E V; Dieriks, Birger V; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2016-08-25

    Polysialated neural cell adhesion molecule (PSA-NCAM) is a membrane bound glycoprotein widely expressed during nervous system development. While commonly described in the neurogenic niches of the adult human brain, there is limited evidence of its distribution in other brain regions. PSA-NCAM is an important regulator of cell-cell interactions and facilitates cell migration and plasticity. Recent evidence suggests these functions may be altered in neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). This study provides a detailed description of the PSA-NCAM distribution throughout the human brain and quantitatively compares the staining load in cortical regions and sub-cortical structures between the control, AD and PD brain. Our results provide evidence of widespread, yet specific, PSA-NCAM expression throughout the human brain including regions devoid of PSA-NCAM in the rodent brain such as the caudate nucleus (CN) and cerebellum (CB). We also detected a significant reduction in PSA-NCAM load in the entorhinal cortex (EC) of cases that was inversely correlated with hyperphosphorylated tau load. These results demonstrate that PSA-NCAM-mediated structural plasticity may not be limited to neurogenic niches and is conserved in the aged brain. We also provide evidence that PSA-NCAM is reduced in the EC, a region severely affected by AD pathology. PMID:27282086

  14. The Role of ATP in the Regulation of NCAM Function

    Hübschmann, Martin; Skladchikova, Galina

    2008-01-01

    Extracellular ATP is an abundant signaling molecule that has a number of functions in the nervous system. It is released by both neurons and glial cells, activates purinergic receptors and acts as a trophic factor as well as a neurotransmitter. In this review, we summarize the evidence for a direct...... ATP-NCAM interaction and discuss its functional implications. The ectodomain of NCAM contains the ATP binding Walker motif A and has intrinsic ATPase activity, which could modulate NCAM-dependent signaling processes. NCAM interacts directly with and signals through FGFR. The NCAM binding site to ATP...... overlaps with the site of NCAM-FGFR interaction, and ATP is capable of disrupting NCAM-FGFR binding. This implies that NCAM signaling through FGFR can be regulated by ATP, which is supported by the observation that ATP can abrogate NCAM-induced neurite outgrowth. Finally, ATP can induce NCAM ectodomain...

  15. Experiment K-7-18: Effects of Spaceflight in the Muscle Adductor Longus of Rats Flown in the Soviet Biosatellite Cosmos 2044. Part 1; A Study Employing Neural Cell Adhesion Molecules (N-CAM) Immunocytochemistry and Conventional Morphological Techniques (Light and Electron Microscopy)

    Daunton, N. G.; DAmelio, F.; Wu, L.; Ilyina-Kakueva, E. I.; Krasnov, I. B.; Hyde, T. M.; Sigworth, S. K.

    1994-01-01

    The effects of spaceflight upon the 'slow' muscle adductor longus was examined in rats flown in the Soviet Biosatellite COSMOS 2044. Three groups - synchronous, vivarium and basal served as controls. The techniques employed included standard methods for light microscopy, N-CAM immunocytochemistry and electron microscopy. Light microscopic observations revealed myofiber atrophy, contraction bands and segmental necrosis accompanied by cellular infiltrates composed of macrophages, leucocytes and mononuclear cells. N-CAM immunoreactivity was seen (N-CAM-IR) on the myofiber surface, satellite cells and in regenerating myofibers reminiscent of myotubes. Ultrastructural alterations included Z band streaming, disorganization of myofibrillar architecture, sarcoplasmic degradation, extensive segmental necrosis with preservation of the basement membrane, degenerative phenomena of the capillary endothelium and cellular invasion of necrotic areas. Regenerating myofibers were identified by the presence of increased amounts of ribosomal aggregates and chains of polyribosomes associated with myofilaments that displayed varied distributive patterns. The principal electron microscopic changes of the neuromuscular junctions consisted of a decrease or absence of synaptic vesicles, degeneration of axon terminals, increased number of microtubules, vacant axonal spaces and axonal sprouting. The present observations indicate that major alterations such as myofibrillar disruption and necrosis, muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight.

  16. Gene Expression Profiling of NCAM NCAM-L1 N-Cadherin-in Ninjurin-1 and Ninjurin-2 during the Course of Differentiation of Murine Neural Stem Cells

    Abbas Ahmadi

    2010-01-01

    Full Text Available Objective: To evaluate and compare the gene expression profiles of Ninjurin-1 and Ninjurin-2 with the expressions of L1 family of cell adhesion molecules (NCAM-L1, neuralcell adhesion molecules (NCAM, and N-cadherin during the course of neural differentiationof mouse neural stem cells (NSCs.Materials and Methods: Briefly, for neural stem cell isolation, the frontal part of an adultmouse brain was minced in phosphate buffered saline (PBS and digested by an enzymesolution which contained hyaluronidase and trypsin. Isolated cells were culturedin medium supplemented by epidermal growth factor (EGF and basic fibroblast growthfactor (bFGF. After seven days, primary neurospheres appeared in culture medium. Aftertransfer to poly-L-ornithine coated dishes that contained culture medium supplementedwith 1% fetal bovine serum (FBS, the primary neurospheres differentiated into neural-likeand neuroglial-like cells. Differentiated cells were examined by morphological, immunocytochemical,and molecular evaluations.Results: Our results showed that isolated cells from the preventricular area of mouseadult brain proliferated in medium which contained EGF and bFGF, and expansion of thecells continued until passage 14 without losing morphological and neurogenesis capacity.Multiple passaging confirmed the stemness nature of the isolated cells. The isolatedNSCs were able to differentiate into neural-like and neuroglial-like cells after transfer topoly-L-ornithine coated dishes that contained culture medium supplemented with 1%FBS. Molecular studies for NCAM, NCAM-L1, and N-Cadherin genes, as well as immunocytochemicalanalysis for NCAM-L1 and NCAM proved the differentiation. Our dataalso revealed, for the first time, gene expression profiling of Ninurin-1 and Ninjurin-2, twonovel cell adhesion molecules (CAMs, during the course of differentiation of neural stemcells.Conclusion: The induction of neural differentiation in mouse NSCs initiates the expressionof NCAM-L1

  17. Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture

    1988-01-01

    The involvement of the adhesion molecules L1, N-CAM, and J1 in adhesion and neurite outgrowth in the peripheral nervous system was investigated. We prepared Schwann cells and fibroblasts (from sciatic nerves) and neurons (from dorsal root ganglia) from 1-d mice. These cells were allowed to interact with each other in a short-term adhesion assay. We also measured outgrowth of dorsal root ganglion neurons on Schwann cell and fibroblast monolayers. Schwann cells (which express L1, N-CAM, and J1)...

  18. Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture.

    Seilheimer, B; Schachner, M

    1988-07-01

    The involvement of the adhesion molecules L1, N-CAM, and J1 in adhesion and neurite outgrowth in the peripheral nervous system was investigated. We prepared Schwann cells and fibroblasts (from sciatic nerves) and neurons (from dorsal root ganglia) from 1-d mice. These cells were allowed to interact with each other in a short-term adhesion assay. We also measured outgrowth of dorsal root ganglion neurons on Schwann cell and fibroblast monolayers. Schwann cells (which express L1, N-CAM, and J1) adhered most strongly to dorsal root ganglion neurons by an L1-dependent mechanism and less by N-CAM and J1. Schwann cell-Schwann cell adhesion was mediated by L1 and N-CAM, but not J1. Adhesion of fibroblasts (which express N-CAM, but not L1 or J1) to neurons or Schwann cells was mediated by L1 and N-CAM and not J1. However, inhibition by L1 and N-CAM antibodies was found to be less pronounced with fibroblasts than with Schwann cells. N-CAM was also strongly involved in fibroblast-fibroblast adhesion. Neurite outgrowth was most extensive on Schwann cells and less on fibroblasts. A difference in extent of neurite elongation was seen between small- (10-20 microns) and large- (20-35 microns) diameter neurons, with the larger neurons tending to exhibit longer neurites. Fab fragments of polyclonal L1, N-CAM, and J1 antibodies exerted slightly different inhibitory effects on neurite outgrowth, depending on whether the neurites were derived from small or large neurons. L1 antibodies interfered most strikingly with neurite outgrowth on Schwann cells (inhibition of 88% for small and 76% for large neurons), while no inhibition was detectable on fibroblasts. Similarly, although to a smaller extent than L1, N-CAM appeared to be involved in neurite outgrowth on Schwann cells and not on fibroblasts. Antibodies to J1 only showed a very small effect on neurite outgrowth of large neurons on Schwann cells. These observations show for the first time that identified adhesion molecules are potent

  19. Effect of Cell Adhesion Molecules on the Neurite Outgrowth of Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons.

    Peng, Su-Ping; Schachner, Melitta; Boddeke, Erik; Copray, Sjef

    2016-04-01

    Intrastriatal transplantation of dopaminergic neurons has been shown to be a potentially very effective therapeutic approach for the treatment of Parkinson's disease (PD). With the detection of induced pluripotent stem cells (iPSCs), an unlimited source of autologous dopaminergic (DA) neurons became available. Although the iPSC-derived dopaminergic neurons exhibited most of the fundamental dopaminergic characteristics, detailed analysis and comparison with primary DA neurons have shown some aberrations in the expression of genes involved in neuronal development and neurite outgrowth. The limited outgrowth of the iPSC-derived DA neurons may hamper their potential application in cell transplantation therapy for PD. In the present study, we examined whether the forced expression of L1 cell adhesion molecule (L1CAM) and polysialylated neuronal cell adhesion molecule (PSA-NCAM), via gene transduction, can promote the neurite formation and outgrowth of iPSC-derived DA neurons. In cultures on astrocyte layers, both adhesion factors significantly increased neurite formation of the adhesion factor overexpressing iPSC-derived DA neurons in comparison to control iPSC-derived DA neurons. The same tendency was observed when the DA neurons were plated on postnatal organotypic striatal slices; however, this effect did not reach statistical significance. Next, we examined the neurite outgrowth of the L1CAM- or PSA-NCAM-overexpressing iPSC-derived DA neurons after implantation in the striatum of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, the animal model for PD. Like the outgrowth on the organotypic striatal slices, no significant L1CAM- and PSA-NCAM-enforced neurite outgrowth of the implanted DA neurons was observed. Apparently, induced expression of L1CAM or PSA-NCAM in the iPSC-derived DA neurons cannot completely restore the neurite outgrowth potential that was reduced in these DA neurons as a consequence of epigenetic aberrations resulting from the i

  20. Synaptic Cell Adhesion Molecules in Alzheimer's Disease

    Leshchyns'ka, Iryna

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity. Genetic studies and biochemical analysis of the human brain tissue, cerebrospinal fluid, and sera from AD patients indicate that levels and function of synaptic cell adhesion molecules are affected in AD. Synaptic cell adhesion molecules interact with Aβ, a peptide accumulating in AD brains, which affects their expression and synaptic localization. Synaptic cell adhesion molecules also regulate the production of Aβ via interaction with the key enzymes involved in Aβ formation. Aβ-dependent changes in synaptic adhesion affect the function and integrity of synapses suggesting that alterations in synaptic adhesion play key roles in the disruption of neuronal networks in AD. PMID:27242933

  1. Enzymatic Depletion of the Polysialic Acid Moiety Associated with the Neural Cell Adhesion Molecule Inhibits Antidepressant Efficacy.

    Wainwright, Steven R; Barha, Cindy K; Hamson, Dwayne K; Epp, Jonathan R; Chow, Carmen; Lieblich, Stephanie E; Rutishauser, Urs; Galea, Liisa Am

    2016-05-01

    Antidepressant drugs are too often ineffective, the exact mechanism of efficacy is still ambiguous, and there has been a paucity of novel targets for pharmacotherapy. In an attempt to understand the pathogenesis of depression and subsequently develop more efficacious antidepressant drugs, multiple theories have been proposed, including the modulation of neurotransmission, the upregulation of neurogenesis and neurotrophic factors, normalizing hypothalamic-pituitary-adrenal reactivity, and the reduction of neuroinflammation; all of which have supporting lines of evidence. Therefore, an ideal molecular target for novel pharmaceutical intervention would function at the confluence of these theories. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) functions broadly, serving to mediate synaptic plasticity, neurogenesis, neurotrophic factor signaling, and inflammatory signaling throughout the brain; all of which are associated with the pathophysiology and treatment of depression. Moreover, the expression of PSA-NCAM is reduced by depression, and conversely enhanced by antidepressant treatment, particularly within the hippocampus. Here we demonstrate that selectively cleaving the polysialic acid moiety, using the bacteriophage-derived enzyme endoneuraminidase N, completely inhibits the antidepressant efficacy of the selective-serotonin reuptake inhibitor fluoxetine (FLX) in a chronic unpredictable stress model of depression. We also observe a corresponding attenuation of FLX-induced hippocampal neuroplasticity, including decreased hippocampal neurogenesis, synaptic density, and neural activation. These data indicate that PSA-NCAM-mediated neuroplasticity is necessary for antidepressant action; therefore PSA-NCAM represents an interesting, and novel, target for pharmacotherapy. PMID:26530284

  2. Effect of NCAM on aged-related deterioration in vision.

    Luke, Margaret Po-Shan; LeVatte, Terry L; O'Reilly, Amanda M; Smith, Benjamin J; Tremblay, François; Brown, Richard E; Clarke, David B

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging. PMID:27103522

  3. The Role of Immunoglobulin Superfamily Cell Adhesion Molecules in Cancer Metastasis

    Chee Wai Wong

    2012-01-01

    Full Text Available Metastasis is a major clinical problem and results in a poor prognosis for most cancers. The metastatic pathway describes the process by which cancer cells give rise to a metastatic lesion in a new tissue or organ. It consists of interconnecting steps all of which must be successfully completed to result in a metastasis. Cell-cell adhesion is a key aspect of many of these steps. Adhesion molecules belonging to the immunoglobulin superfamily (Ig-SF commonly play a central role in cell-cell adhesion, and a number of these molecules have been associated with cancer progression and a metastatic phenotype. Surprisingly, the contribution of Ig-SF members to metastasis has not received the attention afforded other cell adhesion molecules (CAMs such as the integrins. Here we examine the steps in the metastatic pathway focusing on how the Ig-SF members, melanoma cell adhesion molecule (MCAM, L1CAM, neural CAM (NCAM, leukocyte CAM (ALCAM, intercellular CAM-1 (ICAM-1 and platelet endothelial CAM-1 (PECAM-1 could play a role. Although much remains to be understood, this review aims to raise the profile of Ig-SF members in metastasis formation and prompt further research that could lead to useful clinical outcomes.

  4. Regulation of cellular adhesion molecule expression in murine oocytes,peri-implantation and post-implantation embryos

    DAVID; P; LU; LINA; TIAN; CHRIS; O'; NEILL; NICHOLAS; JC; KING

    2002-01-01

    Expression of the adhesion molecules, ICAM-1, VCAM-1, NCAM, CD44, CD49d (VLA-4, α chain),and CD11a (LFA-1, α chain) on mouse oocytes, and pre- and peri-implantation stage embryos was exam-ined by quantitative indirect immunofluorescence microscopy. ICAM-1 was most strongly expressed at theoocyte stage, gradually declining almost to undetectable levels by the expanded blastocyst stage. NCAM,also expressed maximally on the oocyte, declined to undetectable levels beyond the morula stage. On theother hand, CD44 declined from highest expression at the oocyte stage to show a second maximum at thecompacted 8-cell/morula. This molecule exhibited high expression around contact areas between trophecto-derm and zona pellucida during blastocyst hatching. CD49d was highly expressed in the oocyte, remainedsignificantly expressed throughout and after blastocyst hatching was expressed on the polar trophecto-derm. Like CD44, CD49d declined to undetectable levels at the blastocyst outgrowth stage. Expression ofboth VCAM-1 and CD11a was undetectable throughout. The diametrical temporal expression pattern ofICAM-1 and NCAM compared to CD44 and CD49d suggest that dynamic changes in expression of adhesionmolecules may be important for interaction of the embryo with the maternal cellular environment as wellas for continuing development and survival of the early embryo.

  5. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    Park, Kyoung Ho [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Troy, Frederic A., E-mail: fatroy@ucdavis.edu [Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis, CA 95616 (United States); Xiamen University, School of Medicine, Xiamen City (China)

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  6. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders

  7. Mouse Brain PSA-NCAM Levels Are Altered by Graded-Controlled Cortical Impact Injury

    Craig S. Budinich

    2012-01-01

    Full Text Available Traumatic brain injury (TBI is a worldwide endemic that results in unacceptably high morbidity and mortality. Secondary injury processes following primary injury are composed of intricate interactions between assorted molecules that ultimately dictate the degree of longer-term neurological deficits. One comparatively unexplored molecule that may contribute to exacerbation of injury or enhancement of recovery is the posttranslationally modified polysialic acid form of neural cell adhesion molecule, PSA-NCAM. This molecule is a critical modulator of central nervous system plasticity and reorganization after injury. In this study, we used controlled cortical impact (CCI to produce moderate or severe TBI in the mouse. Immunoblotting and immunohistochemical analysis were used to track the early (2, 24, and 48 hour and late (1 and 3 week time course and location of changes in the levels of PSA-NCAM after TBI. Variable and heterogeneous short- and long-term increases or decreases in expression were found. In general, alterations in PSA-NCAM levels were seen in the cerebral cortex immediately after injury, and these reductions persisted in brain regions distal to the primary injury site, especially after severe injury. This information provides a starting point to dissect the role of PSA-NCAM in TBI-related pathology and recovery.

  8. Caspr2 : possible synaptogenic cell adhesion molecule

    Do, Trinh Thuy

    2011-01-01

    Synapses are crucial for communication among neurons in the central nervous system. Contactin-associated protein- like 2 (Caspr2) is a neuronal protein that is a member of the neurexin superfamily and is found in the juxtaparanodal regions of myelinated axons. Caspr2 has also been found in synapses and therefore is also thought to function as a cell adhesion molecule. As such, it should also induce synaptogenesis in vitro similar to the interaction between neurexins (located presynaptically) ...

  9. PSA-NCAM in the posterodorsal medial amygdala is necessary for the pubertal emergence of attraction to female odors in male hamsters.

    Job, Martin O; Cooke, Bradley M

    2015-09-01

    During puberty, attention turns away from same-sex socialization to focus on the opposite sex. How the brain mediates this change in perception and motivation is unknown. Polysialylated neural cell adhesion molecule (PSA-NCAM) virtually disappears from most of the central nervous system after embryogenesis, but it remains elevated in discrete regions of the adult brain. One such brain area is the posterodorsal subnucleus of the medial amygdala (MePD). The MePD has been implicated in male sexual attraction, measured here as the preference to investigate female odors. We hypothesize that PSA-NCAM gates hormone-dependent plasticity necessary for the emergence of males' attraction to females. To evaluate this idea, we first measured PSA-NCAM levels across puberty in several brain regions, and identified when female odor preference normally emerges in male Syrian hamsters. We found that MePD PSA-NCAM staining peaks shortly before the surge of pubertal androgen and the emergence of preference. To test the necessity of PSA-NCAM for female odor preference, we infused endo-neuraminidase-N into the MePD to deplete it of PSAs before female odor preference normally appears. This blocked female odor preference, which suggests that PSA-NCAM facilitates behaviorally relevant, hormone-driven plasticity. PMID:26335887

  10. Cell adhesion molecules: detection with univalent second antibody

    1980-01-01

    Identification of cell surface molecules that play a role in cell-cell adhesion (here called cell adhesion molecules) has been achieved by demonstrating the inhibitory effect of univalent antibodies that bind these molecules in an in vitro assay of cell-cell adhesion. A more convenient reagent, intact (divalent) antibody, has been avoided because it might agglutinate the cells rather than blocking cell-cell adhesion. In this report, we show that intact rabbit immunoglobulin directed against c...

  11. Soluble adhesion molecules in human cancers: sources and fates.

    Kilsdonk, J.W.J. van; Kempen, L.C.L.T. van; Muijen, G.N.P. van; Ruiter, D.J.; Swart, G.W.

    2010-01-01

    Adhesion molecules endow tumor cells with the necessary cell-cell contacts and cell-matrix interactions. As such, adhesion molecules are involved in cell signalling, proliferation and tumor growth. Rearrangements in the adhesion repertoire allow tumor cells to migrate, invade and form metastases. Be

  12. Immune receptors and adhesion molecules in human pulmonary leptospirosis.

    Del Carlo Bernardi, Fabiola; Ctenas, Bruno; da Silva, Luiz Fernando Ferraz; Nicodemo, Antonio Carlos; Saldiva, Paulo Hilário Nascimento; Dolhnikoff, Marisa; Mauad, Thais

    2012-10-01

    Pulmonary involvement in leptospirosis has been increasingly reported in the last 20 years, being related to the severity and mortality of the disease. The pathogenesis of pulmonary hemorrhage in leptospirosis is not understood. Lung endothelial cells have been proposed as targets in the pathogenesis of lung involvement in leptospirosis through the activation of Toll-like receptor 2 or the complement system, which stimulates the release of cytokines that lead to the activation of adhesion molecules. The aim of this study was to investigate the involvement of immune pathways and of the intercellular and vascular cell adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule, respectively) in the lungs of patients with pulmonary involvement of leptospirosis. We studied the lungs of 18 patients who died of leptospirosis and compared them with 2 groups of controls: normal and noninfectious hemorrhagic lungs. Using immunohistochemistry and image analysis, we quantified the expression of the C3a anaphylatoxin receptor, intercellular adhesion molecule, vascular cell adhesion molecule, and Toll-like receptor 2 in small pulmonary vessels and in the alveolar septa. There was an increased expression of intercellular adhesion molecule (P < .03) and C3a anaphylatoxin receptor (P < .008) in alveolar septa in the leptospirosis group compared with the normal and hemorrhagic controls. In the vessels of the leptospirosis group, there was an increased expression of intercellular adhesion molecule (P = .004), vascular cell adhesion molecule (P = .030), and Toll-like receptor 2 (P = .042) compared with the normal group. Vascular cell adhesion molecule expression in vessels was higher in the leptospirosis group compared with the hemorrhagic group (P = .015). Our results indicate that immune receptors and adhesion molecules participate in the phenomena leading to pulmonary hemorrhage in leptospirosis. PMID:22436623

  13. The influence of tobacco smoking on adhesion molecule profiles

    Palmer RM

    2002-01-01

    Full Text Available Abstract Sequential interactions between several adhesion molecules and their ligands regulate lymphocyte circulation and leukocyte recruitment to inflammatory foci. Adhesion molecules are, therefore, central and critical components of the immune and inflammatory system. We review the evidence that tobacco smoking dysregulates specific components of the adhesion cascade, which may be a common factor in several smoking-induced diseases. Smoking causes inappropriate leukocyte activation, leukocyte-endothelial adhesion, and neutrophil entrapment in the microvasculature, which may help initiate local tissue destruction. Appropriate inflammatory reactions may thus be compromised. In addition to smoke-induced alterations to membrane bound endothelial and leukocyte adhesion molecule expression, which may help explain the above phenomena, smoking has a profound influence on circulating adhesion molecule profiles, most notably sICAM-1 and specific sCD44 variants. Elevated concentrations of soluble adhesion molecules may simply reflect ongoing inflammatory processes. However, increasing evidence suggests that specific soluble adhesion molecules are immunomodulatory, and that alterations to soluble adhesion molecule profiles may represent a significant risk factor for several diverse diseases. This evidence is discussed herein.

  14. The intimate relationship of gonadotropin-releasing hormone neurons with the polysialylated neural cell adhesion molecule revisited across development and adult plasticity.

    Franceschini, Isabelle; Desroziers, Elodie; Caraty, Alain; Duittoz, Anne

    2010-12-01

    The neurohormone gonadotropin-releasing hormone (GnRH) is critical for all the aspects of reproductive life in vertebrates. GnRH is secreted by a small number of neurons dispersed within the preoptic-hypothalamic region. These neurons are derived from the embryonic olfactory pit. They then migrate along olfactory, vomeronasal and terminal nerves to their final destination. Classical approaches to study the regulation of GnRH secretion during the reproductive cycle have focused on the various neuronal inputs on GnRH neurons and their regulation by ovarian steroids. However, it is well known that steroids will change the microenvironment of neuronal networks and can induce plasticity and functional changes. In this review, we will focus on the intimate relationship of developing and adult GnRH neurons with the polysialylated form of neural cell adhesion molecule (PSA-NCAM), a major molecular actor in the morphogenesis and adult plasticity of the nervous system. We will first recapitulate the spatiotemporal relationship between PSA-NCAM and migrating GnRH neurons during embryogenesis of various vertebrate species and discuss its importance for GnRH neuron development as shown by various loss of function studies. In the adult, we will review the relationships between PSA-NCAM and GnRH neurons across various physiological states, and open the discussion to the use of new model systems that can help to unravel the function and mechanism of action of PSA-NCAM on GnRH neuronal network activity and GnRH release. PMID:21143658

  15. Cell adhesion molecules in the central nervous system

    Togashi, Hideru; Sakisaka, Toshiaki; Takai, Yoshimi

    2009-01-01

    Cell-cell adhesion molecules play key roles at the intercellular junctions of a wide variety of cells, including interneuronal synapses and neuron-glia contacts. Functional studies suggest that adhesion molecules are implicated in many aspects of neural network formation, such as axon-guidance, synapse formation, regulation of synaptic structure and astrocyte-synapse contacts. Some basic cell biological aspects of the assembly of junctional complexes of neurons and glial cells resemble those ...

  16. Cell adhesion molecules during odontogenesis and tooth-related diseases

    Heymann, Robert

    2002-01-01

    Cell adhesion molecules play essential roles in the development and disease of tooth and oral structures, as well as in the maintenance of adult tissue structure/function. It has been shown that different types of cell adhesion molecules (CAMs) play an important part in craniofacial development when ectomesenchymal cells migrate from the neural list to the primitive oral cavity, giving rise to the palatal processes and tooth germs. The role of CAMs in craniofacial developmen...

  17. Angiogenic Effect of Intercellular Adhesion Molecule-1

    DENG Chenguo; ZHANG Duanlian; SHAN Shengguo; WU Jingwen; YANG Hong; YU Ying

    2007-01-01

    In order to investigate the angiogenic effect of intercellular adhesion molecule-1 (ICAM-1), two parts of experiment were performed. Chick embryo chorioallantoic membrane (CAM) assay was used for in vivo angiogenic research. The chick embryos were divided into 4 groups: ICAM-1 group (divided into 3 subgroups, Ⅰ, Ⅱ and Ⅲ) for screening the angiogenic effect of ICAM-1 by adding different concentrations of ICAM-1 (0.1, 0.2 and 0.3 μg/μL) 5 μL into the chick embryo CAMs on the day 10 after incubation for every subgroup; Anti-ICAM-1 group A (divided into 2 subgroups, Ⅰ and Ⅱ) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 μL into the chick embryo CAMs on the day 10 after incubation for every subgroup to evaluate the effect of ICAM-1 on the survival of microvessels through observing whether Anti-ICAM-1 could induce involution of the microvessels on CAMs; Anti-ICAM-1 group B (divided into 2 subgroups, Ⅰ and Ⅱ ) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 μL into the chick embryo CAMs on the day 6 after incubation for every subgroup to evaluate whether ICAM-1 involved in embryonic angiogenesis through observing the growth of microvessels on CAMs; Control group: ICAM-1 or Anti-ICAM-1 was substituted by PBS 5 μL on the day 10 or day 6 after incubation. Three days later, the CAMs were photographed in vivo, excised, sectioned and the number of microvessels was counted. In ICAM-1 group, there was increased number of microvessels arranged radially with "spoked-wheel" pattern around the gelatin sponges. The new microvessels growing perpendicularly to gelatin sponges were observed. The number of the microvessels growing in the CAM mesenchymes around the sponges in 3 subgroups was higher than that in control group (P<0.01), however, there was no significant difference among the 3 subgroups (P>0.05). In anti-ICAM-1 group A, the radially arranged microvessels were very unclear around the sponges contrast to that of ICAM

  18. The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats

    Rajabzadeh Aliakbar

    2012-05-01

    Full Text Available Abstract Background Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM, which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring. Methods Forty timed-pregnant Wistar rats were divided into four groups: A Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy rats that received repeated intraperitoneal (i.p. pentylenetetrazol, PTZ injections on gestational days (GD 14-19; B Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry. Results Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001 and Kind-/Seiz+ (p = 0.001 groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007 and Kind-/Seiz+ (p = 0.007 group’s newborns on both PD1 and 14. Conclusion Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.

  19. The role of adhesion molecule NCAM in ovarian cancer progression and its correlation with intrabdominal cancer dissemination

    Sanguineti,

    2011-01-01

    Ovarian cancer is a highly metastatic disease and the leading cause of death from gynecologic malignancies. In 2009 in the United States, it was estimated that ovarian cancer will have been diagnosed in 21,550 women with an estimated 14,600 deaths per year (NCI program 2010). The majority of these deaths are from ovarian cancer of the serous histological type and around half of women who are diagnosed with ovarian cancer are 60 or older. Genetic predisposition for familial early-onset bre...

  20. Intact transmembrane isoforms of the neural cell adhesion molecule are released from the plasma membrane

    Olsen, M; Krog, L; Edvardsen, K;

    1993-01-01

    density-gradient centrifugation it was shown that shed transmembrane NCAM-B was present in fractions of high, as well as low, density, indicating that a fraction of the shed NCAM is associated with minor plasma membrane fragments. Finally, it was shown that isolated soluble NCAM inhibited cell binding to......-s1 and NCAM-s2 and the function of soluble NCAM forms were investigated. It was shown that all three soluble forms could be released from brain membranes with M(r) values identical to the three major membrane-associated forms: the large transmembrane 190,000-M(r) form (NCAM-A), the smaller...... intact soluble form from membranes of cells transfected with this isoform. Thus, NCAM-s1 and NCAM-s2 probably represent intact released transmembrane NCAM-A and NCAM-B. The soluble transmembrane forms are likely to exist in vivo, as NCAM-s1 and NCAM-s2 were readily demonstrated in cerebrospinal fluid. By...

  1. MUC18, a marker of tumor progression in human melanoma, show sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily

    The MUC18 antigen is an integral membrane glycoprotein of 113 kDa whose expression on primary human melanomas correlates with poor prognosis and the development of metastatic disease. MUC18 is expressed only sporadically in benign melanocytic nevi and thin primary melanomas that have a low probability of metastasizing. However, with increasing tumor thickness, MUC18 expression becomes more frequent and it is found on 80% of advanced primary tumors and metastases. MUC18-encoding cDNA clones were obtained by screening a human melanoma phage λ expression library with monoclonal antibodies produced against the denatured antigen. The deduced sequence of 603 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The highest sequence similarity is with a group of nervous system cell adhesion molecules, which includes neural cell adhesion molecule (N-CAM). The close structural relationship with these molecules suggests that MUC18 may also be a developmentally regulated cell adhesion molecule

  2. Pathogenic Actions of Cell Adhesion Molecule 1 in Pulmonary Emphysema and Atopic Dermatitis

    Yoneshige, Azusa; Hagiyama, Man; Fujita, Mitsugu; Ito, Akihiko

    2015-01-01

    Cell adhesion mediated by adhesion molecules is of central importance in the maintenance of tissue homeostasis. Therefore, altered expression of adhesion molecules leads to the development of various tissue disorders involving cell activation, degeneration, and apoptosis. Nevertheless, it still remains unclear what initiates the altered expression of adhesion molecules and how the subsequent pathological cascades proceed. In this regard, cell adhesion molecule 1 (CADM1) is one of the candidat...

  3. Pharmacology of cell adhesion molecules of the nervous system

    Kiryushko, Darya; Bock, Elisabeth; Berezin, Vladimir

    2007-01-01

    Cell adhesion molecules (CAMs) play a pivotal role in the development and maintenance of the nervous system under normal conditions. They also are involved in numerous pathological processes such as inflammation, degenerative disorders, and cancer, making them attractive targets for drug...

  4. Human Cytomegalovirus Infection of Tumor Cells Downregulates NCAM (CD56: A Novel Mechanism for Virus-Induced Tumor Invasiveness'

    Roman A. Blaheta

    2004-07-01

    Full Text Available Pathologic data indicate that human cytomegalovirus (HCMV infection might be associated with the pathogenesis of several human malignancies. However, no definitive evidence of a causal link between HCMV infection and cancer dissemination has been established to date. This study describes the modulation of the invasive behavior of NCAM-expressing tumor cell lines by HCMV. Neuroblastoma (NB cells, persistently infected with the HCMV strain AD169 (UKF-NB-4AD169 and MHH-NB-11AD169, were added to endothelial cell monolayers and adhesion and penetration kinetics were measured. The 140- and 180-kDa isoforms of the adhesion receptor NCAM were evaluated by flow cytometry, Western blot, and reverse transcriptionpolymerase chain reaction (RT-PCR. The relevance of NCAM for tumor cell binding was proven by treating NB with NCAM antisense oligonucleotides or NCAM transfection. HCMV infection profoundly increased the number of adherent and penetrated NB, compared to controls. Surface expression of NCAM was significantly lower on UKF-NB-4AD169 and MHH-NB-11AD169, compared to mock-infected cells. Western-blot and RT-PCR demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoform. An inverse correlation between NCAM expression and adhesion capacity of NB has been shown by antisense and transfection experiments. We conclude that HCMV infection leads to downregulation of NCAM receptors, which is associated with enhanced tumor cell invasiveness.

  5. Higher-Order Architecture of Cell Adhesion Mediated by Polymorphic Synaptic Adhesion Molecules Neurexin and Neuroligin

    Hiroki Tanaka

    2012-07-01

    Full Text Available Polymorphic adhesion molecules neurexin and neuroligin (NL mediate asymmetric trans-synaptic adhesion, which is crucial for synapse development and function. It is not known whether or how individual synapse function is controlled by the interactions between variants and isoforms of these molecules with differing ectodomain regions. At a physiological concentration of Ca2+, the ectodomain complex of neurexin-1 β isoform (Nrx1β and NL1 spontaneously assembled into crystals of a lateral sheet-like superstructure topologically compatible with transcellular adhesion. Correlative light-electron microscopy confirmed extracellular sheet formation at the junctions between Nrx1β- and NL1-expressing non-neuronal cells, mimicking the close, parallel synaptic membrane apposition. The same NL1-expressing cells, however, did not form this higher-order architecture with cells expressing the much longer neurexin-1 α isoform, suggesting a functional discrimination mechanism between synaptic contacts made by different isoforms of neurexin variants.

  6. Growth hormone increases vascular cell adhesion molecule 1 expression

    Hansen, Troels Krarup; Fisker, Sanne; Dall, Rolf;

    2004-01-01

    We investigated the impact of GH administration on endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, in vivo and in vitro. Soluble VCAM-1, E-selectin, and C-reactive protein concentrations were measured before and after treatment in 25 healthy subjects and...... 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline...... levels of VCAM-1, but not E-selectin, were significantly lower in GHD patients than in healthy subjects (362 +/- 15 microg/liter vs. 516 +/- 21 microg/liter, P < 0.001) and increased in GHD patients during GH treatment, compared with placebo [net difference between groups 151.8 microg/liter (95...

  7. Calsyntenins Function as Synaptogenic Adhesion Molecules in Concert with Neurexins

    Ji Won Um; Gopal Pramanik; Ji Seung Ko; Min-Young Song; Dongmin Lee; Hyun Kim; Kang-Sik Park; Thomas C. Südhof; Katsuhiko Tabuchi; Jaewon Ko

    2014-01-01

    Multiple synaptic adhesion molecules govern synapse formation. Here, we propose calsyntenin-3/alcadein-β as a synapse organizer that specifically induces presynaptic differentiation in heterologous synapse-formation assays. Calsyntenin-3 (CST-3) was highly expressed during various postnatal periods of mouse brain development. The simultaneous knockdown of all three CSTs, but not CST-3 alone, decreased inhibitory, but not excitatory, synapse densities in cultured hippocampal neurons. Moreover,...

  8. Characterization of NCAM diversity in cultured neurons

    Gegelashvili, George; Andersson, A M; Schousboe, Arne;

    1993-01-01

    A single transcript of the NCAM gene undergoes differential processing resulting in a multiplicity of mRNAs and their translation products. In this study, the diversity of NCAM in rat primary neuronal cultures was investigated utilizing immuno- and Northern blot analyses. NCAM polypeptides of 190 k......Da (NCAM-A) and 135 kDa (NCAM-B) were shown to be associated with the neuronal phenotype. These data were confirmed by Northern blotting, which in both neocortical neurons and cerebellar granule neurons revealed mRNA classes of 7.4 kb and 6.7 kb encoding for NCAM-A and -B, respectively. However......, oligonucleotide probes, specific for selected exons or exon combinations, revealed special features of cerebellar granule neurons as compared to neocortical neurons: expression of 4.3 kb NCAM mRNA, a relatively low amount of VASE-containing variants, and an apparent lack of mRNA species containing exons alpha and...

  9. A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL

    Downer, Eric J; Cowley, Thelma R; Lyons, Anthony;

    2010-01-01

    novel anti-inflammatory agent. Administration of FGL to aged rats attenuated the increased expression of markers of activated microglia, the increase in pro-inflammatory interleukin-1beta (IL-1beta) and the impairment in long-term potentiation (LTP). We report that the age-related increase in microglial......Age-related cognitive deficits in hippocampus are correlated with neuroinflammatory changes, typified by increased pro-inflammatory cytokine production and microglial activation. We provide evidence that the neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as a...... CD200 in vitro. We provide evidence that the increase in CD200 is reliant on IL-4-induced extracellular signal-regulated kinase (ERK) signal transduction. These findings provide the first evidence of a role for FGL as an anti-inflammatory agent and identify a mechanism by which FGL controls...

  10. Adhesion Molecules Associated with Female Genital Tract Infection

    Li, Lin-Xi; Carrascosa, José Manuel; Cabré, Eduard; Dern, Olga; Sumoy, Lauro; Requena, Gerard; McSorley, Stephen J.

    2016-01-01

    Efforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes. PMID:27272720

  11. Direct observation of catch bonds involving cell-adhesion molecules

    Marshall, Bryan T.; Long, Mian; Piper, James W.; Yago, Tadayuki; McEver, Rodger P.; Zhu, Cheng

    2003-05-01

    Bonds between adhesion molecules are often mechanically stressed. A striking example is the tensile force applied to selectin-ligand bonds, which mediate the tethering and rolling of flowing leukocytes on vascular surfaces. It has been suggested that force could either shorten bond lifetimes, because work done by the force could lower the energy barrier between the bound and free states (`slip'), or prolong bond lifetimes by deforming the molecules such that they lock more tightly (`catch'). Whereas slip bonds have been widely observed, catch bonds have not been demonstrated experimentally. Here, using atomic force microscopy and flow-chamber experiments, we show that increasing force first prolonged and then shortened the lifetimes of P-selectin complexes with P-selectin glycoprotein ligand-1, revealing both catch and slip bond behaviour. Transitions between catch and slip bonds might explain why leukocyte rolling on selectins first increases and then decreases as wall shear stress increases. This dual response to force provides a mechanism for regulating cell adhesion under conditions of variable mechanical stress.

  12. NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells.

    Takase, Nobuhisa; Koma, Yu-Ichiro; Urakawa, Naoki; Nishio, Mari; Arai, Noriaki; Akiyama, Hiroaki; Shigeoka, Manabu; Kakeji, Yoshihiro; Yokozaki, Hiroshi

    2016-09-28

    Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immunosuppression of various cancers, including esophageal squamous cell carcinomas (ESCCs). To elucidate the roles of TAMs in ESCCs, we compared the gene expression profiles between human peripheral blood monocyte-derived macrophage-like cells (Macrophage_Ls) and Macrophage_Ls stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAM_Ls) using cDNA microarray analysis. Among the highly expressed genes in TAM_Ls, we focused on neural cell adhesion molecule (NCAM). NCAM knockdown in TAM_Ls revealed a significant decrease of migration and survival via a suppression of PI3K-Akt and fibroblast growth factor receptor 1 (FGFR1) signaling. Stimulation by TECM up-regulated the level of FGFR1 in Macrophage_Ls. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAM_Ls and TE-cells through FGFR1 signaling. Our immunohistochemical analysis of 70 surgically resected ESCC samples revealed that the up-regulated FGF-2 in stromal cells, including macrophages, was associated with more aggressive phenotypes and a high number of infiltrating M2 macrophages. These findings may indicate a novel role of NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of ESCCs. PMID:27317650

  13. Effects of taurine depletion on cell migration and NCAM expression in cultures of dissociated mouse cerebellum and N2A cells

    Maar, T E; Lund, Trine Meldgaard; Gegelashvili, G;

    1998-01-01

    Cultures of dissociated cerebellum from 5- to 6-day-old mice as well as of the N2A neuronal cell line were exposed to guanidino ethane sulfonate (GES, 2-5 mM) to reduce the cellular taurine content. Control cultures were kept in culture medium or medium containing 2-5 mM GES plus 2-5 mM taurine to...... restore the intracellular taurine content. Taurine depletion led to changes in the expression of certain splice variants of NCAM mRNA such as the AAG and the VASE containing forms, while no differences were seen in the expression of the three forms of NCAM protein. In the N2A cells taurine depletion led...... to a decreased migration rate of the cells. The results suggest that the reduced migration rate of neurons caused by taurine depletion may be correlated to changes in expression of certain adhesion molecules such as NCAM. Moreover, taurine appears to be involved in regulation of transcription...

  14. Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion

    Nan-Hong Tang; Yan-Ling Chen; Xiao-Qian Wang; Xiu-Jin Li; Feng-Zhi Yin; Xiao-Zhong Wang

    2004-01-01

    AIM: To explore the cooperative effects of antisense oligonucleotide (ASON) of cell adhesion molecules and cimetidine on the expression of E-selectin and ICAM-1 in endothelial cells and their adhesion to tumor cells.METHODS: After treatment of endothelial cells with ASON and/or cimetidine and induction with TNF-α, the protein and mRNA changes of E-selectin and ICAM-1 in endothelial cells were examined by flow cytometry and RT-PCR,respectively. The adhesion rates of endothelial cells to tumor cells were measured by cell adhesion experiment.RESULTS: In comparison with TNF-α inducing group, lipoASON and lipo-ASON/cimetidine could significantly decrease the protein and mRNA levels of E-selectin and ICAM-1 in endothelial cells, and lipo-ASON/cimetidine had most significant inhibitory effect on E-selectin expression (from 36.37±1.56% to 14.23±1.07%, P<0.001). Meanwhile,cimetidine alone could inhibit the expression of E-selectin (36.37±1.56% vs 27.2±1.31%, P<0.001), but not ICAM-1 (69.34±2.50% vs68.07±2.10%,P>O.05)and the two kinds of mRNA, either. Compared with TNF-αα inducing group, the rate of adhesion was markedly decreased in lipo-E-selectin ASON and lipo-E-selectin ASON/cimetidine treated groups(P<0.05),and Jipo-E-selectin ASON/cimetidine worked better than lipo-E-selectin ASON alone except for HepG2/ECV304 group(P<0.05). However, the decrease of adhesion was not significant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidine treated groups except for HepG2/ECV304 group (P >0.05).CONCLUSION: These data demonstrate that ASON in combination with cimetidine in vitro can significantly reduce the adhesion between endothelial cells and hepatic or colorectal cancer cells, which is stronger than ASON or cimetidine alone. This study provides some useful proofs for gene therapy of antiadhesion.

  15. Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study

    de Maat, Moniek; Bots, Michiel; Breteler, Monique; Meijer, John; Kiliaan, Amanda; Witteman, Jacqueline; Hofman, Albert

    2002-01-01

    textabstractInflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 part...

  16. Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca

    Catarina F. P. Teixeira; Stella R. Zamuner

    2002-01-01

    It has been shown that Bothrops jararaca venom (BjV) induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-alpha, interleukin (I...

  17. The conveyor belt hypothesis for thymocyte migration: participation of adhesion and de-adhesion molecules

    Villa-Verde D.M.S.

    1999-01-01

    Full Text Available Thymocyte differentiation is the process by which bone marrow-derived precursors enter the thymus, proliferate, rearrange the genes and express the corresponding T cell receptors, and undergo positive and/or negative selection, ultimately yielding mature T cells that will represent the so-called T cell repertoire. This process occurs in the context of cell migration, whose cellular and molecular basis is still poorly understood. Kinetic studies favor the idea that these cells leave the organ in an ordered pattern, as if they were moving on a conveyor belt. We have recently proposed that extracellular matrix glycoproteins, such as fibronectin, laminin and type IV collagen, among others, produced by non-lymphoid cells both in the cortex and in the medulla, would constitute a macromolecular arrangement allowing differentiating thymocytes to migrate. Here we discuss the participation of both molecules with adhesive and de-adhesive properties in the intrathymic T cell migration. Functional experiments demonstrated that galectin-3, a soluble ß-galactoside-binding lectin secreted by thymic microenvironmental cells, is a likely candidate for de-adhesion proteins by decreasing thymocyte interaction with the thymic microenvironment.

  18. Fluoxetine Increases the Expression of NCAM140 and pCREB in Rat C6 Glioma Cells

    Choi, Mi Ran; Oh, Dong Hoon; Kim, Seok Hyeon; Jung, Kyoung Hwa; Das, Nando Dulal

    2012-01-01

    Objective Dysfunction of neural plasticity in the brain is known to alter neural networks, resulting in depression. To understand how fluoxetine regulates molecules involved in neural plasticity, the expression levels of NCAM, NCAM140, CREB and pCREB, in rat C6 glioma cells after fluoxetine treatment were examined. Methods C6 cells were cultured after 20 min or after 6, 24 or 72 h treatments with 10 µM fluoxetine. Immunocytochemistry was used to determine the effect of fluoxetine on the expression of NCAM. Western blot analysis was used to measure the expression levels of NCAM140 and CREB and the induction of pCREB after fluoxetine treatment. Results NCAM expression following 72-h fluoxetine treatment was significantly increased around cell membranes compared to control cells. Cells treated with fluoxetine for 6 and 72 h showed a significant increase in NCAM140 expression compared to cells treated for 20 min. The level of pCREB in the cells treated with fluoxetine for 72 h not only increased more than 60%, but was also significantly different when compared with the other treatment times. The 72-h fluoxetine treatment led to the increase of NCAM140 and the phosphorylation of CREB in C6 cells. Conclusion Our findings indicate that fluoxetine treatment regulates neuronal plasticity and neurite outgrowth by phosphorylating and activating CREB via the NCAM140 homophilic interaction-induced activation of the Ras-MAPK pathway. PMID:22707970

  19. Cell adhesion molecule control of planar spindle orientation.

    Tuncay, Hüseyin; Ebnet, Klaus

    2016-03-01

    Polarized epithelial cells align the mitotic spindle in the plane of the sheet to maintain tissue integrity and to prevent malignant transformation. The orientation of the spindle apparatus is regulated by the immobilization of the astral microtubules at the lateral cortex and depends on the precise localization of the dynein-dynactin motor protein complex which captures microtubule plus ends and generates pulling forces towards the centrosomes. Recent developments indicate that signals derived from intercellular junctions are required for the stable interaction of the dynein-dynactin complex with the cortex. Here, we review the molecular mechanisms that regulate planar spindle orientation in polarized epithelial cells and we illustrate how different cell adhesion molecules through distinct and non-overlapping mechanisms instruct the cells to align the mitotic spindle in the plane of the sheet. PMID:26698907

  20. Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation

    Ali, Shahina; Kaur, Jaswinder; Patel, Kamala D.

    2000-01-01

    Eosinophils are usually associated with parasitic and allergic diseases; however, eosinophilia is also observed in several types of human tumors, including breast carcinomas. In this study we examined several human breast carcinoma cell lines for adhesion molecule expression and the ability to bind and activate eosinophils. MDA-MB-435S and MDA-MB-468 cells constitutively expressed both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and this expressio...

  1. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules

    1991-01-01

    Cytokines such as interleukin 1 (IL-1) promote adhesiveness in human umbilical vein endothelial cells for leukocytes including basophils, eosinophils, and neutrophils, and induce expression of adherence molecules including ICAM-1 (intercellular adhesion molecule-1), ELAM-1 (endothelial-leukocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1). In the present study, blocking monoclonal antibodies (mAb) recognizing ICAM-1, ELAM-1, and VCAM-1 have been used to compare their ...

  2. Correlation of Serum Concentrations of Soluble Thrombomodulin, Soluble Vascular Cell Adhesion Molecule-1,Intracellular Adhesion Molecule -1 And E-Selectin In Patients WithSystemic Lupus Erythematosus

    Malak., A. Mohsen*, Magda.A.Gamil*,Maha. I.Shehata

    2003-01-01

    To date no specific serological parameters are available to assess disease activity in systemic lupus erythematosus (SLE). The objective of this study was to correlate serum levels of thrombomodulin (TM), intracellular adhesion molecule-1 sICAM-1, vascular cell adhesion molecule-1 sVCAM-1, and E-selectin with standard laboratory tests and clinical indices of disease activity in 40 patients with SLE and 20 apparently healthy persons as controls. According to British Isles Lupus Assessment Grou...

  3. Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules.

    Yamazaki, T; Seko, Y; Tamatani, T; Miyasaka, M.; Yagita, H; Okumura, K.; R. Nagai; Yazaki, Y

    1993-01-01

    To elucidate the mechanism(s) of myocardial reperfusion injury, we investigated the roles of cell adhesion molecules on both leukocytes and vascular endothelial cells in the reperfused myocardia. We found that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia and clarified, for the first time, that the expression of intercellular adhesion molecule-1 was enhanced on the capillary and venous endothelial cells from 8 to 96 ...

  4. Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids

    Ballabh, P; Simm, M; Kumari, J; Krauss, A; Jain, A.; Califano, C; Lesser, M.; Cunningham-Rundle..., S

    2004-01-01

    Aims: To study a longitudinal change in the expression of adhesion molecules CD11b, CD18, and CD62L on neutrophils and monocytes in very low birth weight babies who develop respiratory distress syndrome, to compare these levels between bronchopulmonary dysplasia (BPD) and non-BPD infants, and to assess the effect of corticosteroid treatment on these adhesion molecules.

  5. Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line

    Holland, J; Owens, T

    1997-01-01

    Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B...

  6. Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules

    1989-01-01

    The leukocyte CD11/CD18 adhesion molecules (beta 2 integrins) are a family of three heterodimeric glycoproteins each with a distinct alpha subunit (CD11a, b, or c) and a common beta subunit (CD18). CD11/CD18 mediate crucial leukocyte adhesion functions such as chemotaxis, phagocytosis, adhesion to endothelium, aggregation, and cell-mediated cytotoxicity. The enhanced cell adhesion observed upon activation of leukocytes is associated with increased surface membrane expression of CD11/CD18, as ...

  7. The cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules

    Halberg, Kenneth A; Rainey, Stephanie M; Veland, Iben R; Neuert, Helen; Dornan, Anthony J; Klämbt, Christian; Davies, Shireen-Anne; Dow, Julian A T

    2016-01-01

    Multicellular organisms rely on cell adhesion molecules to coordinate cell-cell interactions, and to provide navigational cues during tissue formation. In Drosophila, Fasciclin 2 (Fas2) has been intensively studied due to its role in nervous system development and maintenance; yet, Fas2 is most...... role for this well-known cell adhesion molecule, and propose that Fas2-mediated intermicrovillar homophilic adhesion complexes help stabilize the brush border....

  8. Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.

    Kataria, Hardeep; Lutz, David; Chaudhary, Harshita; Schachner, Melitta; Loers, Gabriele

    2016-09-01

    Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery after injury, leading to severe disabilities in motor functions and pain. Peripheral nerve injury impairs motor, sensory, and autonomic functions, particularly in cases where nerve gaps are large and chronic nerve injury ensues. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration after acute injury. We screened libraries of known drugs for small molecule agonists of L1 and evaluated the effect of hit compounds in cell-based assays in vitro and in mice after femoral nerve and spinal cord injuries in vivo. We identified eight small molecule L1 agonists and showed in cell-based assays that they stimulate neuronal survival, neuronal migration, and neurite outgrowth and enhance Schwann cell proliferation and migration and myelination of neurons in an L1-dependent manner. In a femoral nerve injury mouse model, enhanced functional regeneration and remyelination after application of the L1 agonists were observed. In a spinal cord injury mouse model, L1 agonists improved recovery of motor functions, being paralleled by enhanced remyelination, neuronal survival, and monoaminergic innervation, reduced astrogliosis, and activation of microglia. Together, these findings suggest that application of small organic compounds that bind to L1 and stimulate the beneficial homophilic L1 functions may prove to be a valuable addition to treatments of nervous system injuries. PMID:26253722

  9. Effects of protein tyrosine kinase inhibitors on cytokine-induced adhesion molecule expression by human umbilical vein endothelial cells.

    May, M. J.; Wheeler-Jones, C. P.; Pearson, J. D.

    1996-01-01

    1. Endothelial cells can be stimulated by the pro-inflammatory cytokines interleukin (IL)-1 alpha and tumour necrosis factor (TNF) alpha to express the leukocyte adhesion molecules E-selectin, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 but the intracellular signalling mechanisms leading to this expression are incompletely understood. We have investigated the role of protein tyrosine kinases (PTK) in adhesion molecule expression by cytokine-activated ...

  10. Intercellular adhesion molecule-1 in patients with idiopathic interstitial pneumonia.

    Takehara H

    2001-08-01

    Full Text Available This study focuses on a possible role of intercellular adhesion molecule-1 (ICAM-1 in interstitial pulmonary diseases. We determined a soluble form of ICAM-1 in serum and bronchoalveolar lavage fluid (BALF using ELISA in patients with usual interstitial pneumonia (UIP, bronchiolitis obliterance organizing pneumonia (BOOP, or nonspecific interstitial pneumonia (NSIP. In addition, we investigated the expression of ICAM-1 in the lung tissues of these patients by means of immunohistochemical staining. Serum levels of soluble ICAM-1 were significantly higher in patients with UIP or NSIP than in healthy subjects, and were also high in patients with BOOP. The soluble ICAM-1 in BALF tended to be higher in patients with UIP, BOOP, or NSIP than in normal subjects. A significant correlation was seen between soluble levels of ICAM-1 in serum and BALF. In the immunostaining of ICAM-1 of the lung tissues, ICAM-1 expression was more pronounced in patients with UIP than in those with BOOP or NSIP. The increased expression of ICAM-1 was seen in type II alveolar epithelium and vascular endothelium in patients with interstitial pneumonia. A positive correlation was observed between the degree of ICAM-1 expression in the lung tissues and the BALF levels of soluble ICAM-1. The expression of ICAM-1 in type II alveolar epithelium suggests that ICAM-1 plays a specific role in the fibrotic process of the lung, and that the measurement of soluble ICAM-1 in sera and BALF could be a useful marker for evaluating the progression of fibrosis.

  11. Activated leukocyte cell adhesion molecule in breast cancer: prognostic indicator

    Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value. The immunohistochemical distribution and location of ALCAM was assessed in normal breast tissue and carcinoma. The levels of ALCAM transcripts in frozen tissue (normal breast, n = 32; breast cancer, n = 120) were determined using real-time quantitative PCR. The results were then analyzed in relation to clinical data including the tumor type, the grade, the nodal involvement, distant metastases, the tumor, node, metastasis (TNM) stage, the Nottingham Prognostic Index (NPI), and survival over a 6-year follow-up period. Immunohistochemical staining on tissue sections in ducts/acini in normal breast and in breast carcinoma was ALCAM-positive. Differences in the number of ALCAM transcripts were found in different types of breast cancer. The level of ALCAM transcripts was lower (P = 0.05) in tumors from patients who had metastases to regional lymph nodes compared with those patients without, in higher grade tumors compared with Grade 1 tumors (P < 0.01), and in TNM Stage 3 tumors compared with TNM Stage 1 tumors (P < 0.01). Tumors from patients with poor prognosis (with NPI > 5.4) had significantly lower levels (P = 0.014) of ALCAM transcripts compared with patients with good prognosis (with NPI < 3.4), and tumors from patients with local recurrence had significantly lower levels than those patients without local recurrence or metastases (P = 0.04). Notably, tumors from patients who died of breast cancer had significantly lower levels of ALCAM transcripts (P = 0.0041) than those with primary tumors but no metastatic disease or local recurrence. Patients with low levels of ALCAM transcripts had significantly (P = 0.009) more incidents (metastasis, recurrence, death) compared with patients with primary breast tumors with high levels of

  12. Homophilic Adhesion Mechanism of Neurofascin, a Member of the L1 Family of Neural Cell Adhesion Molecules

    Liu, Heli; Focia, Pamela J.; He, Xiaolin (NWU, MED)

    2012-02-13

    The L1 family neural cell adhesion molecules play key roles in specifying the formation and remodeling of the neural network, but their homophilic interaction that mediates adhesion is not well understood. We report two crystal structures of a dimeric form of the headpiece of neurofascin, an L1 family member. The four N-terminal Ig-like domains of neurofascin form a horseshoe shape, akin to several other immunoglobulin superfamily cell adhesion molecules such as hemolin, axonin, and Dscam. The neurofascin dimer, captured in two crystal forms with independent packing patterns, reveals a pair of horseshoes in trans-synaptic adhesion mode. The adhesion interaction is mediated mostly by the second Ig-like domain, which features an intermolecular {beta}-sheet formed by the joining of two individual GFC {beta}-sheets and a large but loosely packed hydrophobic cluster. Mutagenesis combined with gel filtration assays suggested that the side chain hydrogen bonds at the intermolecular {beta}-sheet are essential for the homophilic interaction and that the residues at the hydrophobic cluster play supplementary roles. Our structures reveal a conserved homophilic adhesion mode for the L1 family and also shed light on how the pathological mutations of L1 affect its structure and function.

  13. Short-term effect of adrenalin on S-100b and N-CAM level in the different rat brain areas

    Y. P. Kovalchuk

    2015-09-01

    Full Text Available The level of adrenalin grows under stress conditions, sense of danger, anxiety, fear, trauma, burns and shock. In high concentrations adrenaline increases the speed of protein catabolism. Working through the circulatory system, adrenaline affects almost all the functions of organs, causing the body mobilization to counter stressful situations. Due to ELISA the astrocytes-specific protein (S-100b and neural cell adhesion molecule (N-CAM were studied. S-100b is produced mainly by astrocytes іn the brain and depending on the concentration it causes trophic or toxic effect on the neurons and glial cells.Strong stress and ischemia induce re-distribution of calcium-binding protein S-100b and elevation of its level. Quantitative changes of S-100b under the influence of various factors on the body which lead to the metabolic disorder in the brain are considered today as a sign of brain damage (cortical, ischemic one, etc.. Fluctuations in the concentration of S-100b in the brain are not always accompanied by marked deterioration of the physical condition of animals, but they can also lead to a number of violations of integrative functions of the brain depending on over-production of this protein. Most N-CAM are transmembrane proteins that cross the plasma membraneonce; intracellular domains have different size and it is thought they are involved in binding to cytoskeleton or cell signaling. Violation of N-CAM functions leads to disruption of nerve sprouts. Data obtained in our study showed no serious re-distribution of S-100b and N-CAM level in the different areas of rat brain (cerebral cortex, hippocampus and thalamus under effect of adrenalin administered to the animals (under skin in dosage of 0.45–0.60 mg per rat, 1 time per day during 10 days, probably because of the type of injection and/or short time of adrenalin action. Increased dosage of adrenaline 1 hour before decapitation leads to the decrease of level of total protein in membrane

  14. Activated leukocyte cell adhesion molecule and prognosis in acute ischemic stroke

    Smedbakken, Linda; Jensen, Jesper K; Hallén, Jonas;

    2011-01-01

    Biomarkers predicting mortality and functional outcome in stroke may be clinically helpful in identification of patients likely to benefit from intervention. Activated leukocyte cell adhesion molecule (ALCAM) is upregulated during neuroinflammation; we investigated whether ALCAM concentrations ar...

  15. Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study

    M.P.M. de Maat (Moniek); M.L. Bots (Michiel); M.M.B. Breteler (Monique); J. Meijer (John); A.J. Kiliaan (Amanda); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2002-01-01

    textabstractInflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), i

  16. Modulation of lens cell adhesion molecules by particle beams

    McNamara, M. P.; Bjornstad, K. A.; Chang, P. Y.; Chou, W.; Lockett, S. J.; Blakely, E. A.

    2001-01-01

    Cell adhesion molecules (CAMs) are proteins which anchor cells to each other and to the extracellular matrix (ECM), but whose functions also include signal transduction, differentiation, and apoptosis. We are testing a hypothesis that particle radiations modulate CAM expression and this contributes to radiation-induced lens opacification. We observed dose-dependent changes in the expression of beta 1-integrin and ICAM-1 in exponentially-growing and confluent cells of a differentiating human lens epithelial cell model after exposure to particle beams. Human lens epithelial (HLE) cells, less than 10 passages after their initial culture from fetal tissue, were grown on bovine corneal endothelial cell-derived ECM in medium containing 15% fetal bovine serum and supplemented with 5 ng/ml basic fibroblast growth factor (FGF-2). Multiple cell populations at three different stages of differentiation were prepared for experiment: cells in exponential growth, and cells at 5 and 10 days post-confluence. The differentiation status of cells was characterized morphologically by digital image analysis, and biochemically by Western blotting using lens epithelial and fiber cell-specific markers. Cultures were irradiated with single doses (4, 8 or 12 Gy) of 55 MeV protons and, along with unirradiated control samples, were fixed using -20 degrees C methanol at 6 hours after exposure. Replicate experiments and similar experiments with helium ions are in progress. The intracellular localization of beta 1-integrin and ICAM-1 was detected by immunofluorescence using monoclonal antibodies specific for each CAM. Cells known to express each CAM were also processed as positive controls. Both exponentially-growing and confluent, differentiating cells demonstrated a dramatic proton-dose-dependent modulation (upregulation for exponential cells, downregulation for confluent cells) and a change in the intracellular distribution of the beta 1-integrin, compared to unirradiated controls. In contrast

  17. Homophilic interaction of the L1 family of cell adhesion molecules

    Wei, Chun Hua; Ryu, Seong Eon

    2012-01-01

    Homophilic interaction of the L1 family of cell adhesion molecules plays a pivotal role in regulating neurite outgrowth and neural cell networking in vivo. Functional defects in L1 family members are associated with neurological disorders such as X-linked mental retardation, multiple sclerosis, low-IQ syndrome, developmental delay, and schizophrenia. Various human tumors with poor prognosis also implicate the role of L1, a representative member of the L1 family of cell adhesion molecules, and...

  18. Expression of Adhesion Molecules in Synovia of Patients with Treatment-Resistant Lyme Arthritis

    Akin, Evren; Aversa, John; Steere, Allen C.

    2001-01-01

    The expression of adhesion molecules in synovium in patients with Lyme arthritis is surely critical in the control of Borrelia burgdorferi infection but may also have pathologic consequences. For example, molecular mimicry between a dominant T-cell epitope of B. burgdorferi outer surface protein A and an adhesion molecule, human lymphocyte function-associated antigen 1 (LFA-1), has been implicated in the pathogenesis of treatment-resistant Lyme arthritis. Using immunohistochemical methods, we...

  19. N-Glycosylation at the SynCAM (Synaptic Cell Adhesion Molecule) Immunoglobulin Interface Modulates Synaptic Adhesion

    A Fogel; Y Li; Q Wang; T Lam; Y Modis; T Biederer

    2011-12-31

    Select adhesion molecules connect pre- and postsynaptic membranes and organize developing synapses. The regulation of these trans-synaptic interactions is an important neurobiological question. We have previously shown that the synaptic cell adhesion molecules (SynCAMs) 1 and 2 engage in homo- and heterophilic interactions and bridge the synaptic cleft to induce presynaptic terminals. Here, we demonstrate that site-specific N-glycosylation impacts the structure and function of adhesive SynCAM interactions. Through crystallographic analysis of SynCAM 2, we identified within the adhesive interface of its Ig1 domain an N-glycan on residue Asn(60). Structural modeling of the corresponding SynCAM 1 Ig1 domain indicates that its glycosylation sites Asn(70)/Asn(104) flank the binding interface of this domain. Mass spectrometric and mutational studies confirm and characterize the modification of these three sites. These site-specific N-glycans affect SynCAM adhesion yet act in a differential manner. Although glycosylation of SynCAM 2 at Asn(60) reduces adhesion, N-glycans at Asn(70)/Asn(104) of SynCAM 1 increase its interactions. The modification of SynCAM 1 with sialic acids contributes to the glycan-dependent strengthening of its binding. Functionally, N-glycosylation promotes the trans-synaptic interactions of SynCAM 1 and is required for synapse induction. These results demonstrate that N-glycosylation of SynCAM proteins differentially affects their binding interface and implicate post-translational modification as a mechanism to regulate trans-synaptic adhesion.

  20. Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis

    Jian-Min Su; Li-Ying Wang; Yu-Long Liang; Xi-Liang Zha

    2005-01-01

    AIM: Cell adhesion molecules and their signal molecules play a very important role in carcinogenesis. The aim of this study is to elucidate the role of these molecules and the signal molecules of integrins and E-cadherins, such as (focal adhesion kinase) FAK, (integrin linked kinase)ILK, and β-catenin in hepatocellular carcinoma cell apoptosis.METHODS: We first synthesized the small molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it, by element analysis and 1H NMR. To establish the apoptosis model of the SMMC-7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for different concentrations or for various length times in the presence of 20 μmol/L N,N-diphenyl-p-phenylenediamine,which blocks necrotic cell death and identified this model by flow cytometry and DNA ladder. Then we studied the changes of FAK, ILK, β-catenin, and PKB in this apoptotic model by Western blot.RESULTS: We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC-7721 hepatocellular carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or decrease of FAK, ILK, PKB, and β-catenin or the damage of cell-matrix and cell-cell adhesion.CONCLUSION: Our results suggested that the decrease of adhesion signal molecules, FAK, ILK, PKB, and β-catenin,could induce hepatocellular carcinoma cell apoptosis.

  1. Targeting Endothelial Adhesion Molecule Transcription for Treatment of Inflammatory Disease: A Proof-of-Concept Study

    Liam M. Ashander

    2016-01-01

    Full Text Available Targeting the endothelial adhesion molecules that control leukocyte trafficking into a tissue has been explored as a biological therapy for inflammatory diseases. However, these molecules also participate in leukocyte migration for immune surveillance, and inhibiting the physiological level of an adhesion molecule might promote infection or malignancy. We explored the concept of targeting endothelial adhesion molecule transcription during inflammation in a human system. Intercellular adhesion molecule 1 (ICAM-1 mediates leukocyte migration across the retinal endothelium in noninfectious posterior uveitis. We observed an increase in the transcription factor, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1, in parallel with ICAM-1, in human retinal endothelial cells treated with tumor necrosis factor-alpha (TNF-α, and identified putative binding sites for NF-κB1 within the ICAM-1 regulatory region. We targeted induced NF-κB1 expression in endothelial cells with small interfering (siRNA. Knockdown of NF-κB1 significantly decreased cell surface expression of ICAM-1 protein induced by TNF-α but did not reduce constitutive ICAM-1 expression. Consistently, NF-κB1 knockdown significantly reduced leukocyte binding to cell monolayers in the presence of TNF-α but did not impact baseline binding. Findings of this proof-of-concept study indicate that induced transcription of endothelial adhesion molecules might be targeted therapeutically for inflammatory disease in humans.

  2. [The expression level of adhesion molecules on neutrophils depending at segmentation of their nuclei].

    Kashutin, S L; Danilov, S I; Vereshchagina, E N; Kluchareva, S V

    2013-11-01

    The article deals with results of detection of expression level of adhesion molecules on neutrophils and segmentation of their nuclei. It is established that in conditions of absence of antigen stimulation neutrophils of circulating pool express molecules of L-selectin in 53.34%, LFA-1 molecules in 65.64%, ICAM-1 in 40.51%, LE4-3 in 58.72% and PECAM-1 in 59.74%. The full readiness to realization of phase of sliding, strong adhesion and immediately transmigration itselfis detected in neutrophils with five segments in nucleus. PMID:24640111

  3. Hypertonic saline impedes tumor cell-endothelial cell interaction by reducing adhesion molecule and laminin expression.

    Shields, Conor J

    2012-02-03

    BACKGROUND: Hypertonic saline infusion dampens inflammatory responses and suppresses neutrophil-endothelial interaction by reducing adhesion molecule expression. This study tested the hypothesis that hypertonic saline attenuates tumor cell adhesion to the endothelium through a similar mechanism. METHODS: Human colon cancer cells (LS174T) were transfected with green fluorescent protein and exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 under hypertonic and isotonic conditions for 1 and 4 hours. Confluent human umbilical vein endothelial cells were similarly exposed. Cellular apoptosis and expression of adhesion molecules and laminin were measured by flow cytometry. Tumor cell adhesion to endothelium and laminin was assessed with fluorescence microscopy. Data are represented as mean +\\/- standard error of mean, and an ANOVA test was performed to gauge statistical significance, with P <.05 considered significant. RESULTS: Hypertonic exposure significantly reduced tumor cell adhesion despite the presence of the perioperative cell stressors (42 +\\/- 2.9 vs 172.5 +\\/- 12.4, P <.05), attenuated tumor cell beta-1 integrin (14.43 vs 23.84, P <.05), and endothelial cell laminin expression (22.78 +\\/- 2.2 vs 33.74 +\\/- 2.4, P <.05), but did not significantly alter cell viability. CONCLUSION: Hypertonic saline significantly attenuates tumor cell adhesion to endothelium by inhibiting adhesion molecule and laminin expression. This may halt the metastatic behavior of tumor cells shed at surgery.

  4. The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology.

    Winter, M.J.; Nagtegaal, I.D.; Krieken, J.H.J.M. van; Litvinov, S.V.

    2003-01-01

    Cell adhesion receptors (CAMs) are actively involved in regulating various cell processes, including growth, differentiation, and cell death. Therefore, CAMs represent a large group of morphoregulating molecules, mediating cross-talk between cells and of cells with their environment. From this persp

  5. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  6. Cell surface molecules and fibronectin-mediated cell adhesion: effect of proteolytic digestion of membrane proteins

    1982-01-01

    Proteases have been used as a tool to investigate the role of surface molecules in fibronectin-mediated cell adhesion. Proteolytic digestion of membrane-proteins by pronase (1 mg/ml for 20 min at 37 degrees C) completely inhibited adhesion of baby hamster kidney (BHK) fibroblasts on fibronectin-coated plastic dishes. Various degrees of inhibition were also obtained after treatment with proteinase K, chymotrypsin, papain, subtilopeptidase A, and thermolysin. Protein synthesis was required to r...

  7. Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis

    Fazly, Ahmed; Jain, Charu; Dehner, Amie C.; Issi, Luca; Lilly, Elizabeth A.; Ali, Akbar; Cao, Hong; Fidel, Paul L.; P. Rao, Reeta; Kaufman, Paul D.

    2013-01-01

    Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm forma...

  8. Optimization of adhesion mode atomic force microscopy resolves individual molecules in topography and adhesion

    Willemsen, O.H.; Snel, M.M.E.; Noort, van S.J.T.; Werf, van der K.O.; Grooth, de B.G.; Figdor, C.G.; Greve, J.

    1999-01-01

    The force sensor of an atomic force microscope (AFM) is sensitive enough to measure single molecular binding strengths by means of a force–distance curve. In order to combine high-force sensitivity with the spatial resolution of an AFM in topography mode, adhesion mode has been developed. Since this

  9. An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons

    Neiiendam, Johanne Louise; Køhler, Lene Boding; Christensen, Claus;

    2004-01-01

    interaction with FGFR in primary cultures of three different neuronal cell types all expressing FGFR subtype 1: dopaminergic, hippocampal and cerebellar granule neurons. Moreover, we show that the FGL peptide promotes neuronal survival upon induction of cell death in the same three cell types. The effects of...... factor receptor (FGFR). NCAM-mediated adhesion leads to activation of various intracellular signal transduction pathways, including the Ras-mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PI3K)-Akt pathways. A synthetic peptide derived from the second fibronectin type III...... module of NCAM, the FGL peptide, binds to and induces phosphorylation of FGFR without prior homophilic NCAM binding. We here present evidence that this peptide is able to mimic NCAM heterophilic binding to the FGFR by inducing neuronal differentiation as reflected by neurite outgrowth through a direct...

  10. The role of the cytokines and cell-adhesion molecules on the immunopathology of acute appendicitis

    To study the local expression of the proinflammatory cytokine such as interferon gamma and anti-inflammatory cytokine like interleukin-10 (IL-10) and their role in cell adhesion molecules (CAM) expression on the surface of endothelial cell at the site of inflammation in acute appendicitis. The local expression of these cytokines and CAM was correlated with clinical findings to shed light on their role in the pathogenesis of acute appendicitis. Thirty-five patients with acute appendicitis and 6 apparently normal appendices were removed incidentally from individuals presented with problems other than appendicitis, were included in this prospective study. They were attendant of the emergency room in Al-Khadhumiyah Teaching Hospital in Baghdad, from October 2003 to September 2004. Cell adhesion molecules (intracellular adhesion molecule-1 [ICAM-l], ICAM-3 and vascular cell adhesion molecule-1 [VCAM-1]) were detected by immunohistochemistry while IL-10 and interferon gamma were detected by in situ hybridization. The specimens were classified into 5 groups; early acute appendicitis, phlegmonous appendicitis, ulcero-phlegmonousappendicitis, and gangrenous appendicitis, and the fifth group included specimens that showed no histopathological changes, defined as histologically normal appendix. Intracellular adhesion molecule-1, VCAM-I, IL-10 and interferon gamma were expressed weakly in the control group, while ICAM-3 was not detected in the control group. The average score for ICAM-I, VCAM-1 and the percentage of cells expressing IL-l0 and interferon gamma were significantly higher in the patient groups when compared with the control group. Intracellular adhesion molecule-3 was expressed in the patient group. The kinetics of CAM expression were tightly correlated to the balance between IL-10 and interferon gamma especially after 12.5 hours from the first symptoms experienced by the patients. The interferon gamma was the main player and the most significant factor that leads

  11. Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits.

    Um, Min Young; Hwang, Kwang Hyun; Choi, Won Hee; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

    2014-10-01

    Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression. PMID:25282128

  12. Plasma treated polyethylene grafted with adhesive molecules for enhanced adhesion and growth of fibroblasts

    The cell–material interface plays a crucial role in the interaction of cells with synthetic materials for biomedical use. The application of plasma for tailoring polymer surfaces is of abiding interest and holds a great promise in biomedicine. In this paper, we describe polyethylene (PE) surface tuning by Ar plasma irradiating and subsequent grafting of the chemically active PE surface with adhesive proteins or motives to support cell attachment. These simple modifications resulted in changed polymer surface hydrophilicity, roughness and morphology, which we thoroughly characterized. The effect of our modifications on adhesion and growth was tested in vitro using mouse embryonic fibroblasts (NIH 3T3 cell line). We demonstrate that the plasma treatment of PE had a positive effect on the adhesion, spreading, homogeneity of distribution and moderately on proliferation activity of NIH 3T3 cells. This effect was even more pronounced on PE coated with biomolecules. - Graphical abstract: High density polyethylene scaffolds (PE) were modified by deposition to Ar plasma. These surface reactive PE were further grafted with biomolecules to enhance cell attachment and proliferation. The changes in surface physico-chemical properties (hydrophilicity, morphology, roughness) of PE were measured. The effects of used substrates on the adhesion and growth of mouse embryonic fibroblasts were determined by a five-day cell culture study. The method for significant biocompatibility improvement was presented. Highlights: ► Argon plasma treatment altered polyethylene surface morphology and roughness ► Plasma treatment reduced contact angle of polyethylene ► Grafting of polyethylene with biomolecules further reduced contact angle ► Plasma treatment and peptide grafting increased polyethylene biocompatibility

  13. Decreased soluble cell adhesion molecules after tirofiban infusion in patients with unstable angina pectoris

    Aliyev Emil

    2004-04-01

    Full Text Available Abstract Aim The inflammatory response, initiated by neutrophil and monocyte adhesion to endothelial cells, is important in the pathogenesis of acute coronary syndromes. Platelets play an important role in inflammatory process by interacting with monocytes and neutrophils. In this study, we investigated the effect of tirofiban on the levels of cell adhesion molecules (soluble intercellular adhesion molecule-1, sICAM-1, and vascular cell adhesion molecule-1, sVCAM-1 in patients with unstable angina pectoris (AP. Methods Thirty-five patients with unstable AP (Group I, ten patients with stable AP (Group II and ten subjects who had angiographycally normal coronary arteries (Group III were included the study. Group I was divided into two subgroups for the specific treatment regimens: Group IA (n = 15 received tirofiban and Group IB (n = 20 did not. Blood samples for investigating the cell adhesion molecules were drawn at zero time (baseline; 0 h in all patients and at 72 h in Group I. Results The baseline levels of sICAM-1 and sVCAM-1 were higher in Group I than in Groups II and III. They were higher in Group IA than in Group IB. However, the sICAM-1 and sVCAM-1 levels decreased significantly in Group IA after tirofiban infusion. In contrast, these levels remained unchanged or were increased above the baseline value in Group IB at 72 h. Conclusion The levels of cell adhesion molecules in patients with unstable AP decreased significantly after tirofiban infusion. Inhibition of platelet function by specific glycoprotein IIb/IIIa antagonists may decrease platelet-mediated inflammation and the ischemic end-point.

  14. Decreased soluble cell adhesion molecules after tirofiban infusion in patients with unstable angina pectoris

    Ercan, Ertugrul; Bozdemir, Huseyin; Tengiz, Istemihan; Sekuri, Cevad; Aliyev, Emil; Akilli, Azem; Akin, Mustafa

    2004-01-01

    Aim The inflammatory response, initiated by neutrophil and monocyte adhesion to endothelial cells, is important in the pathogenesis of acute coronary syndromes. Platelets play an important role in inflammatory process by interacting with monocytes and neutrophils. In this study, we investigated the effect of tirofiban on the levels of cell adhesion molecules (soluble intercellular adhesion molecule-1, sICAM-1, and vascular cell adhesion molecule-1, sVCAM-1) in patients with unstable angina pectoris (AP). Methods Thirty-five patients with unstable AP (Group I), ten patients with stable AP (Group II) and ten subjects who had angiographycally normal coronary arteries (Group III) were included the study. Group I was divided into two subgroups for the specific treatment regimens: Group IA (n = 15) received tirofiban and Group IB (n = 20) did not. Blood samples for investigating the cell adhesion molecules were drawn at zero time (baseline; 0 h) in all patients and at 72 h in Group I. Results The baseline levels of sICAM-1 and sVCAM-1 were higher in Group I than in Groups II and III. They were higher in Group IA than in Group IB. However, the sICAM-1 and sVCAM-1 levels decreased significantly in Group IA after tirofiban infusion. In contrast, these levels remained unchanged or were increased above the baseline value in Group IB at 72 h. Conclusion The levels of cell adhesion molecules in patients with unstable AP decreased significantly after tirofiban infusion. Inhibition of platelet function by specific glycoprotein IIb/IIIa antagonists may decrease platelet-mediated inflammation and the ischemic end-point. PMID:15059285

  15. Activated leukocyte cell adhesion molecule expression predicts lymph node metastasis in oral squamous cell carcinoma.

    Brand, M. van den; Takes, R.P.; Blokpoel-deRuyter, M.; Slootweg, P.J.; Kempen, L.C.L.T. van

    2010-01-01

    Lymphatic metastasis of oral squamous cell carcinoma (SCC) is important for prognosis and clinical decision making concerning the treatment of the neck but may be difficult to detect. Activated leukocyte cell adhesion molecule (ALCAM), has been shown to correlate with prognosis or tumor grade in dif

  16. Persistent downregulation of the pancarcinoma-associated epithelial cell adhesion molecule via active intranuclear methylation

    van der Gun, Bernardina T. F.; Wasserkort, Reinhold; Monami, Amelie; Jeltsch, Albert; Rasko, Tamits; Slaska-Kiss, Krystyna; Cortese, Rene; Rots, Marianne G.; de Leij, Lou F. M. H.; Ruiters, Marcel H. J.; Kiss, Antal; Weinhold, Elmar; McLaughlin, Pamela M. J.

    2008-01-01

    The epithelial cell adhesion molecule (EpCAM) is expressed at high levels on the surface of most carcinoma cells. SiRNA silencing of EpCAM expression leads to reduced metastatic potential of tumor cells demonstrating its importance in oncogenesis and tumor progression. However, siRNA therapy require

  17. Cell adhesion to agrin presented as a nanopatterned substrate is consistent with an interaction with the extracellular matrix and not transmembrane adhesion molecules

    Wolfram Tobias

    2008-12-01

    Full Text Available Abstract Background Molecular spacing is important for cell adhesion in a number of ways, ranging from the ordered arrangement of matrix polymers extracellularly, to steric hindrance of adhesion/signaling complexes intracellularly. This has been demonstrated using nanopatterned RGD peptides, a canonical extracellular matrix ligand for integrin interactions. Cell adhesion was greatly reduced when the RGD-coated nanoparticles were separated by more than 60 nm, indicating a sharp spacing-dependent threshold for this form of cell adhesion. Results Here we show a similar dependence of cell adhesion on the spacing of agrin, a protein that exists as both a secreted, matrix-bound form and a type-2 transmembrane form in vivo. Agrin was presented as a substrate for cell adhesion assays by anchoring recombinant protein to gold nanoparticles that were arrayed at tunable distances onto glass coverslips. Cells adhered well to nanopatterned agrin, and when presented as uniformly coated substrates, adhesion to agrin was comparable to other well-studied adhesion molecules, including N-Cadherin. Adhesion of both mouse primary cortical neurons and rat B35 neuroblastoma cells showed a spacing-dependent threshold, with a sharp drop in adhesion when the space between agrin-coated nanoparticles increased from 60 to 90 nm. In contrast, adhesion to N-Cadherin decreased gradually over the entire range of distances tested (uniform, 30, 60, 90, and 160 nm. The spacing of the agrin nanopattern also influenced cell motility, and peptide competition suggested adhesion was partially integrin dependent. Finally, differences in cell adhesion to C-terminal agrin fragments of different lengths were detected using nanopatterned substrates, and these differences were not evident using uniformly coated substrates. Conclusion These results suggest nanopatterned substrates may provide a physiological presentation of adhesive substrates, and are consistent with cells adhering to agrin

  18. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin V;

    2003-01-01

    kinase (MAPK) pathway and an increase in intracellular Ca2+ levels. Stimulation of neurones with the synthetic NCAM-ligand, C3, induces neurite outgrowth through signalling pathways similar to the pathways activated through physiological, homophilic NCAM-stimulation. We present here data indicating that...... indicating a survival-promoting effect of NCAM-stimulation by C3 on cerebellar and dopaminergic neurones induced to undergo apoptosis. This protective effect of C3 included an inhibition of both DNA-fragmentation and caspase-3 activation. The survival-promoting effect of NCAM-stimulation was also shown to be...

  19. Proanthocyanidins, from Ribes nigrum leaves, reduce endothelial adhesion molecules ICAM-1 and VCAM-1

    Desmecht D

    2005-08-01

    Full Text Available Abstract Background The effects of proanthocyanidins (PACs, isolated from blackcurrant (Ribes nigrum L. leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro. Methods In vivo studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4 mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1 were detected by immunohistochemistry on lung sections. In vitro studies were conducted on endothelial LT2 cells, stimulated with TNF-α, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were examined by one-way analysis of variance (ANOVA followed by a Scheffe post-hoc test. Results Pretreatment of the animals with PACs (10, 30 and 60 mg/kg inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF165 mRNA expression. Moreover, VEGF121 mRNA expression was dose-dependently enhanced. Conclusion This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-α-induced VEGF transcription.

  20. Intercellular Adhesion Molecule-1 Levels in Experimental Brain Injury and the Effects of Alpha-tocopherol

    Nilgun Senol

    2014-06-01

    Full Text Available Aim: The mechanisms, responsible for the secondary injuries occuring after acute injury of the brain are; release of nitrous oxide which is an inflammatory mediator, abnormal formation of free oxygen radicals and excessive stimulation of excitatory aminoacids. In this study, it is aimed to investigate changes in intercellular adhesion molecule levels in the brain, that occur subsequent to blunt head trauma, and after administration of an antioxidant agent, vitamin E. Material and Method: In this study, rats were divided into 4 groups. In group A; rats had only skin incision, group B; rats were traumatized after the skin incision, group C; isotonic (30mg/kg was given intraperitoneally after 30 minutes of the trauma, group D; alpha-tocopherol (30mg/kg was given intraperitoneally, after 30 minutes of the trauma. All the rats in these groups were sacrified after 24 hours. Biparietal and bifrontal lobs were taken about 3x5x1mm tickness and intercellular adhesion molecule-1 levels were studied by enzyme-linked immunosorbent assay kit. Results: As the result of the statistical analysis, it is detected that although there is an increase in intercellular adhesion molecule levels in brain parenchyma after trauma, it is statistically unsignificant. However, as the traumatized group and the group given alpha-tocopherol after trauma was compared, a statistically significant decrease in intercellular adhesion molecule-1 levels in the alpha-tocopherol given group was seen. Discussion: Alpha-tocopherol, an antioxidant agent, causes decrease in intercellular adhesion molecule levels, by decreasing inflammation.

  1. Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca

    Stella R. Zamuner

    2002-01-01

    Full Text Available It has been shown that Bothrops jararaca venom (BjV induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1, LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1 on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-α, interleukin (IL-1 and IL-6 have been investigated. Anti-mouse LECAM-1, LFA-1, ICAM-1 and PECAM-1 monoclonal antibody injection resulted in a reduction of 42%, 80%, 66% and 67%, respectively, of neutrophil accumulation induced by BjV (250 μg/kg, intraperitoneal injection in male mice compared with isotype-matched control injected animals. The anti-mouse CD18 monoclonal antibody had no significant effect on venom-induced neutrophil accumulation. Concentrations of LTB4, TXA2, IL-6 and TNF-α were significant increased in the peritoneal exudates of animals injected with venom, whereas no increment in IL-1 was detected. This results suggest that ICAM-1, LECAM-1, LFA-1 and PECAM-1, but not CD18, adhesion molecules are involved in the recruitment of neutrophils into the inflammatory site induced by BjV. This is the first in vivo evidence that snake venom is able to up-regulate the expression of adhesion molecules by both leukocytes and endothelial cells. This venom effect may be indirect, probably through the release of the inflammatory mediators evidenced in the present study.

  2. Highly sensitivity adhesion molecules detection in hereditary haemochromatosis patients reveals altered expression.

    Norris, S

    2012-02-01

    Several abnormalities in the immune status of patients with hereditary haemochromatosis (HH) have been reported, suggesting an imbalance in their immune function. This may include persistent production of, or exposure to, altered immune signalling contributing to the pathogenesis of this disorder. Adhesion molecules L-, E- and P-Selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) are some of the major regulators of the immune processes and altered levels of these proteins have been found in pathological states including cardiovascular diseases, arthritis and liver cancer. The aim of this study was to assess L-, E- and P-Selectin, ICAM-1 and VCAM-1 expression in patients with HH and correlate these results with HFE mutation status and iron indexes. A total of 139 subjects were diagnosed with HH (C282Y homozygotes = 87, C282Y\\/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 healthy control subjects with no HFE mutation (N\\/N), 18 normal subjects heterozygous for the H63D mutation served as age-sex-matched controls. We observed a significant decrease in L-selectin (P = 0.0002) and increased E-selectin and ICAM-1 (P = 0.0006 and P = 0.0059) expression in HH patients compared with healthy controls. This study observes for the first time that an altered adhesion molecules profile occurs in patients with HH that is associated with specific HFE genetic component for iron overload, suggesting that differential expression of adhesion molecules may play a role in the pathogenesis of HH.

  3. Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery

    Toft, P; Christiansen, K; Tønnesen, Else Kirstine; Nielsen, C H; Lillevang, S

    1997-01-01

    cytometrically using 123-dihydrorhodamine. A panel of adhesion molecules was measured using monoclonal antibodies. Following CPB the oxidative burst activity and the expression of the adhesion molecule L-selectin more than doubled compared to initial values. There was no difference between the steroid group and...

  4. Correlation of Serum Concentrations of Soluble Thrombomodulin, Soluble Vascular Cell Adhesion Molecule-1,Intracellular Adhesion Molecule -1 And E-Selectin In Patients WithSystemic Lupus Erythematosus

    Malak., A. Mohsen*, Magda.A.Gamil*,Maha. I.Shehata

    2003-09-01

    Full Text Available To date no specific serological parameters are available to assess disease activity in systemic lupus erythematosus (SLE. The objective of this study was to correlate serum levels of thrombomodulin (TM, intracellular adhesion molecule-1 sICAM-1, vascular cell adhesion molecule-1 sVCAM-1, and E-selectin with standard laboratory tests and clinical indices of disease activity in 40 patients with SLE and 20 apparently healthy persons as controls. According to British Isles Lupus Assessment Group (BILAG disease activity index, the 40 patients were divided into two groups, the first consisted of 22 with active disease, and the second consisted of 18 patients with inactive SLE. Serum sTM, sICAM-1, sVCAM-I, and E-selectin were measured in their sera, using enzyme linked immuonosorbent assay (ELISA technique.C-reactiv protein (CRP, Erythrocyte sedimentation rates (ESR and serum creatinines were measured by standard laboratory tests. Total leukocytic count and hemoglobin concentration were detected by coulter counter. Levels of sTM and sVCAM were highly elevated in the group of patients with active SLE as compared to the inactive one (P0.05. In SLE, the BILAG disease activity index, ESR and serum creatinine correlated best with sTM, sVCAM-1 and E-selectin levels while there was a weak association between CRP levels and the adhesion molecules, and no correlation between CRP level and disease activity. In conclusion, sTM and sVCAM were the most important serological indices of disease activity in SLE and might be valuable serological parameters for monitoring therapy.

  5. Lysophosphatidic acid regulates adhesion molecules and enhances migration of human oral keratinocytes.

    Thorlakson, Hong H; Schreurs, Olav; Schenck, Karl; Blix, Inger J S

    2016-04-01

    Oral keratinocytes are connected via cell-to-cell adhesions to protect underlying tissues from physical and bacterial damage. Lysophosphatidic acids (LPAs) are a family of phospholipid mediators that have the ability to regulate gene expression, cytoskeletal rearrangement, and cytokine/chemokine secretion, which mediate proliferation, migration, and differentiation. Several forms of LPA are found in saliva and gingival crevicular fluid, but it is unknown how they affect human oral keratinocytes (HOK). The aim of the present study was therefore to examine how different LPA forms affect the expression of adhesion molecules and the migration and proliferation of HOK. Keratinocytes were isolated from gingival biopsies obtained from healthy donors and challenged with different forms of LPA. Quantitative real-time RT-PCR, immunocytochemistry, and flow cytometry were used to analyze the expression of adhesion molecules. Migration and proliferation assays were performed. Lysophosphatidic acids strongly promoted expression of E-cadherin and occludin mRNAs and translocation of E-cadherin protein from the cytoplasm to the membrane. Occludin and claudin-1 proteins were up-regulated by LPA. Migration of HOK in culture was increased, but proliferation was reduced, by the addition of LPA. This indicates that LPA can have a role in the regulation of the oral epithelial barrier by increasing the expression of adhesion molecules of HOK, by promotion of migration and by inhibition of proliferation. PMID:26913569

  6. Adhesion molecule levels in serum and cerebrospinal fluid in children with bacterial meningitis and sepsis

    Soad M Jaber

    2009-01-01

    Full Text Available Background : Adhesion molecules play a role in leukocyte recruitment during central nervous system (CNS inflammation. Aim: This study was designed to compare serum, cerebrospinal fluid (CSF concentrations of adhesion molecules in children with meningitis and sepsis, and to evaluate their sources. Setting : This study was carried out at Pediatric Department, King Abdulaziz University Hospital from January 2007 to June 2008. Design: Serum and CSF samples were collected on admission from meningitis (n = 40, sepsis (n = 20 patients, and sera from controls (n = 20. Materials and Methods : Endothelial (E, leukocyte (L, platelet (P selectins intercellular cell adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecules-1 (VCAM-1 were measured using ELISA. Statistics : ANOVA and Spearman′s correlations were used. Adhesion molecules with albumin concentration were estimated in CSF/serum to calculate concentration quotients. Results : In meningitis, serum sE-, sL-, sP-selectins sICAM-1, sVCAM-1 levels were higher than controls. Compared to sepsis, serum sE-selectin, sL-selectin, sVCAM-1, CSF-sL-selectin, CSF-sVCAM-1, VCAM-1 ratio and index were higher, while serum sP-selectin was lower than meningitis. sE-selectin ratio, CSF sICAM-1 were higher in meningitis with positive than negative culture. The sE-selectin index was higher in meningitis with neurological complication than those without it. In meningitis, correlation was found between CSF protein and CSF white blood cell counts (WBCs, CSF sICAM-1, CSF sVCAM-1 and between CSF sE-selectin and CSF sICAM-1. Conclusions : This study supports the role of adhesion molecules especially sL-selectin, sVCAM-1 in meningitis and suggests further research to determine their use as biomarkers for meningitis and use of their antagonists as therapeutic for CNS inflammation. The presence of discrepancy of CSF/serum ratios for molecules of same molecular weight suggest intrathecal shedding in addition to

  7. INFLUENCE OF SOLUBLE PLACENTAL TISSUE-DERIVED MOLECULES UPON EXPRESSION OF ADHESION MOLECULES BY EA.HY926 ENDOTHELIAL CELLS

    O. I. Stepanova

    2014-07-01

    Full Text Available Abstract.  Leukocyte  recruitment  to  placental  tissue  is  an  important  factor  of  its  development.  In  this respect, adhesion molecules at the endothelial cell surface represent a key determining factor of leukocyte adhesion and their trans-endothelial migration. The goal of investigation was to evaluate changed expression of adhesion molecules on the endothelial cells induced by supernates of placental tissue cultures. Placental tissue supernatants produced by the first- and third-trimester placental tissue from normal pregnancy, as well as from women with gestosis, induced higher expression of CD31, CD9, CD62E, CD62P, CD34, CD54, CD51/61, CD49d  and  integrin  β7  expression  by  endothelial  cells,  as  compared  with  their  baseline  levels.  However, the  supernates  from  pre-eclamptic  placental  tissue (3rd  trimester  caused  an  increased  CD9  expression by  endothelial  cells,  as  compared  with  effects  of placental  supernates  from  eclampsia-free  cases.  Our data  contribute  to  understanding  a  possible  role  of endothelial cell adhesion molecules in recruitment of leukocytes to placental tissue and possible participation of adhesion molecules in pathogenesis of pre-eclampsia. The work was supported by a grant from Russian Ministry of Education and Science ГК №02.740.11.0711 and Presidential grant № НШ-3594.2010.7 and МД-150.2011.7. (Med. Immunol., 2011, vol. 13, N 6, pp 589-596

  8. MONOCYTE ADHESION MOLECULES EXPRESSION IN PATIENTS WITH CHRONIC HEPATITIS C AND LIVER CIRRHOSIS

    Nora E.I. El-Bassiouni

    2013-09-01

    Full Text Available Abstract: Introduction: Chronic viral hepatitis is histologically characterized by predominantly periportal infiltration of mononuclear cells, including monocytes/macrophages. Intralobular infiltration of these inflammatory cells is an ominous sign of deterioration and a criterion for disease activity. We aimed to study the expression of monocytes adhesion molecules and their endothelial ligands in patients with chronic hepatitis C (CHC and liver cirrhosis (LC. The influence of cytokines and chemokine on monocyte adhesion was also taken into account. Material and Methods: The current study included 30 cases of CHC, 30 cases of LC and 15 normal healthy controls. Flow cytometric quantification of CD11a, CD11b and CD49d monocyte surface antigen expression was performed. Circulating sE-selectin, sICAM-1, sVCAM-1, TNF-α, IL-1 and MCP-1 were measured by ELISA kits. Results: The expression of CD11b, CD49d, and the serum level of sICAM-1, sVCAM-1, TNF-α showed progressive increase from non-cirrhotic to cirrhotic patients. correlation was found between monocyte adhesion molecules CD11a, CD11b and CD49d and each of sICAM-1 and sVCAM-1 Conclusions: These findings suggest that the modulation of monocyte-subset recruitment into the liver via adhesion molecules or cytokines/cytokine receptors may represent promising approaches for therapeutic interventions in human liver fibrosis. Measurement of serum soluble adhesion molecules may be useful for monitoring progression of liver inflammation and fibrosis during CHC.

  9. Fluoxetine Increases the Expression of NCAM140 and pCREB in Rat C6 Glioma Cells

    Choi, Mi Ran; Oh, Dong Hoon; Kim, Seok Hyeon; Jung, Kyoung Hwa; Das, Nando Dulal; Chai, Young Gyu

    2012-01-01

    Objective Dysfunction of neural plasticity in the brain is known to alter neural networks, resulting in depression. To understand how fluoxetine regulates molecules involved in neural plasticity, the expression levels of NCAM, NCAM140, CREB and pCREB, in rat C6 glioma cells after fluoxetine treatment were examined. Methods C6 cells were cultured after 20 min or after 6, 24 or 72 h treatments with 10 µM fluoxetine. Immunocytochemistry was used to determine the effect of fluoxetine on the expre...

  10. Surface plasmon-enhanced optical trapping of quantum-dot-conjugated surface molecules on neurons cultured on a plasmonic chip

    Miyauchi, Kohei; Tawa, Keiko; Kudoh, Suguru N.; Taguchi, Takahisa; Hosokawa, Chie

    2016-06-01

    Living neurons in a complex neuronal network communicate with each other through synaptic connections. The molecular dynamics of cell surface molecules localized at synaptic terminals is essential for functional connections via synaptic plasticity in the neuronal network. Here, we demonstrate surface-plasmon-resonance-based optical trapping using a plasmonic chip toward realizing effective manipulation of molecules on the surface of neurons. Surface-plasmon-enhanced optical trapping was evaluated by the fluorescence analysis of nanoparticles suspended in water and neural cell adhesion molecules (NCAMs) labeled with quantum dots (Q-dots) on rat hippocampal neurons. The motion of nanoparticles in water and the molecular dynamics of NCAMs on neuronal cells cultured on a plasmonic chip were constrained at the laser focus more effectively than those on a glass substrate because of the surface plasmon resonance effect.

  11. Soluble fms-like tyrosine kinase-1 and endothelial adhesion molecules (intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) as predictive markers for blood pressure reduction after renal sympathetic denervation.

    Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Rixe, Johannes; Hamm, Christian; Nef, Holger

    2014-05-01

    Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (P<0.001) as were ICAM-1 (P<0.001) and VCAM-1 levels (P<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718-0.921; P<0.001), 0.754 (0.654-0.854; P<0.001), and 0.684 (0.564-804; P=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation. PMID:24470464

  12. Inhibitors of 5-lipoxygenase inhibit expression of intercellular adhesion molecule-1 in human melanoma cells

    Yin WANG; Bin ZHOU; Ji LI; Yong-bing CAO; Xin-sheng CHEN; Ming-he CHENG; Ming YIN

    2004-01-01

    AIM: To study the effect of 5-lipoxygenase inhibitors on the expression of intercellular adhesion molecule-1 (ICAM-1) in melanoma cells. METHODS: ICAM-1 protein of human melanoma cell a375 was detected by enzyme-linked immunosorbent, flow cytometry and Western blot analysis. Level of ICAM-1 mRNA in a375 was evaluated by Northern blot analysis. Adhesion of a375 to endothelial cell EC304 was analyzed by isotopic tracing. RESULTS:5-Lipoxygenase inhibitors nordihydroguaiaretic acid, AA861 and MK886, could suppress the expression of ICAM-1 protein as well as of its mRNA in a375 cells and reduce the adhesion of a375 to EC304. CONCLUSION:5-Lipoxygenase inhibitors can inhibit the expression of ICAM-1 in human melanoma cells and may be valuable for treatment of melanoma metastasis.

  13. Influence of platelet activating factor on expression of adhesion molecules in experimental pancreatitis

    Hua Zhao; Ji-Wei Chen; Ya-Kui Zhou; Xue-Feng Zhou; Pei-Yun Li

    2003-01-01

    AIM: To determine whether Platelet activating factor (PAF)has a regulation role in the expression of adhesion moleculesand accumulation of neutrophils in a murine model of acutepancreatitis.METHODS: One hundred twenty-eight Kunming mice weredivided into four groups. Group 1 received 0.1 mi saline s.c.every hour for three hours (sham). Group 2 received cerulein(50 μg/kg dose s.c.) every hour for three hours. Group 3received AP and additional challenge of PAF (50 rg/kg inabsolute ethanol) (AP/PAF). Group 4 received AP, plustherapeutic treatment with GAB (25 mg dose i.p.) immediatelyafter the first challenge of cerulein (AP/GAB). Animals weresacrificed at 12 h after the first challenge of saline or cerulein.Adhesion molecules of pancreas were semi-quantified bySP methods. Standard assays were performed for serumamylase and myeloperoxidase activity (MPO) of pancreas.Histology of pancreas was scored in a blind manner. Watercontent of pancreas was also measured at the same time.RESULTS: Control pancreata showed negligible adhesionmolecule expression and neutrophil accumulation. Therewere evident adhesion molecules expression and neutrophilaccumulation in AP and AP/PAF compared with sham (P<0.05).AP/GAB had a lower level of adhesion molecules, neutrophils,and water content versus AP and AP/PAF (P<0.05). Histologyshowed a trend toward improvement in AP/GAB, but didnot reach statistical significance.CONCLUSION: PAF can induce the expression of adhesionmolecules that mediate neutrophil accumulation. The PAFantagonist reduces the expression of adhesion moleculesand the severity of inflammation when given immediatelyafter the induction of mild AP in mice. These results suggestthat PAF antagonism may be useful in the treatment of mildpancreatitis after its clinical onset.

  14. Changes of synaptophysin and neural cell adhesion molecule immunopositive substances in hippocampus after fear extinction%条件性恐惧消退与海马突触素、神经细胞黏附分子免疫反应阳性物质的动态变化

    田玉娥; 张燕; 李敏; 王进礼; 刘江杰; 韦美; 李培培; 张丽丽

    2008-01-01

    Objective To study the changes of synaptophysin and neural cell adhesion molecule (NCAM)immunopositive substances in hippocampus after fear extinction.Methods 72 male adult SD rats were randomly divided into natural extinction group,immediate extinction group and 24-hour extinction group.Conditinned fear animal model of rats was established by tone paired foot shock.Fear extinction was trained in 15 minutes or 24-hours after establishment of fear memory.Extinction retention test and immunohistochemistry of synaptophysin and NCAM of hippocampus were done at 1 st,3rd,7th and 20th days after fear extinction.The corrected optical density of the positive synaptophysin and NCAM staining in the hippocampus was measured by the computer natural extinction group,24-hour extinction group was better,it was shorter during the early stage after fear extinction,synaptophysin and NCAM immunopositive substances in hippocampus were increased quickly and reached the highest at 3rd day then decreased for all groups.Synaptophysin and NCAM expressed obviously in 24-hour extinction group at different time after fear extinction,the expression of synaptophysin(0.0140±0.0088,0.0345±0.0076,0.0277±0.0067,0.0112±0.0031,P<0.01),NCAM(0.0235±0.0084,0.0613±0.0057,0.0515±0.0115.0.0249±0.0115,P<0.05 or P<0.01)in hippocampus in rats of 24 hour extinction group were higher than those in natural extinction group.Synaptophysin and NCAM expressed increase in immediate extinction group,but there were no significantly difference between immediate extinction group and natural extinction group.Conclusion Exposure therapy could decrease fear memory and might enhance fear extinction by increase the level of synaptophysin and NCAM in hippocampus,but exposure therapy given in different time show different therapeutic effeets.%目的 研究条件性恐惧消退过程中消退记忆保持成绩与海马神经细胞黏附分子(NCAM)、突触索的动态变化.方法 成年雄性SD大鼠72只,随机

  15. Cadmium exposure, intercellular adhesion molecule-1 and peripheral artery disease: a cohort and an experimental study

    Fagerberg, Björn; Bergström, Göran; Borén, Jan; Barregard, Lars

    2013-01-01

    Objectives Cadmium exposure has been found to be associated with atherosclerotic plaques in the carotid arteries and with circulating levels of the proatherogenic intercellular adhesion molecule-1 (ICAM-1). The research questions were (1) if blood and urinary cadmium levels are associated with low ankle-brachial index (ABI) as a measure of peripheral artery disease in a longitudinal study and (2) if ICAM-1 mediates proatherogenic effects of cadmium exposure. Design A prospective, observationa...

  16. Association between two single base polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease

    Habibi, Manijeh; Naderi, Nosratllah; Farnood, Alma; Balaii, Hedieh; Dadaei, Tahereh; Almasi, Shohreh; Zojaji, Homayoun; Asadzadeh Aghdae, Hamid; Zali, Mohammad Reza

    2016-01-01

    Aim: The present study evaluated the association between G241R and K469E polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease in Iranian population. Background: Inflammatory bowel disease including ulcerative colitis and Crohn’s disease, is a chronic idiopathic inflammatory disease of the gastrointestinal tract. There are two single base polymorphisms of intercellular adhesion molecule 1gene, G241R and K469E, reported to be associated with inflammatory disorders. Patients and methods: In this case-control study, 156 inflammatory bowel disease patients (110 ulcerative colitis and 46 Crohn’s disease patients) and 131 healthy controls were enrolled. Two polymorphisms of intercellular adhesion molecule 1 gene, including G241R and K469E, were assessed by polymerase chain reaction followed by restriction fragment length polymorphism. Results: The E469 allele of K469E polymorphism was significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 1.83; 95% CI: 1.13 to 2.96). The mutant homozygote genotype of K469E polymorphism (E/E) was also significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 4.23; 95% CI: 1.42 to 12.59). No difference was observed in the frequency of K469E polymorphism among ulcerative colitis patients compared to controls. There were no significant differences in genotype and allele frequencies of G241R polymorphism among ulcerative colitis and Crohn’s disease patients compared to control subjects. Conclusion: According to our findings, K469E polymorphism of intercellular adhesion molecule 1 gene may probably participate in the pathogenesis of Crohn’s disease in Iran. PMID:27099667

  17. Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung

    Chapin, Cheryl; Bailey, Nicole A.; Gonzales, Linda W.; Lee, Jae-Woo; Gonzalez, Robert F.; Ballard, Philip L.

    2011-01-01

    Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycophosphatidylinositol-anchored protein expressed in epithelial cells of various primate tissues. It binds gram-negative bacteria and is overexpressed in human cancers. CEACAM6 is associated with lamellar bodies of cultured type II cells of human fetal lung and protects surfactant function in vitro. In this study, we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature ...

  18. Cell surface adhesion molecules and cytokine profiles in primary progressive multiple sclerosis

    Ukkonen, Maritta; Wu, Xingchen; Reipert, Birgit; Dastidar, Prasun; Elovaara, Irina

    2007-01-01

    OBJECTIVE: We evaluated the utility of adhesion molecule (AM) and cytokine/chemokine expressions in blood and cerebrospinal fluid (CSF) as markers of disease activity in primary progressive multiple sclerosis (PPMS). METHODS: The expressions of AMs and the levels of 17 cytokines in patients with...... synthesis of MCP-1 and IL-8 in PPMS indicate the importance of inflammatory changes in the pathogenesis of PPMS....

  19. Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets

    Cicmil, Milenko; Stevens, Jo; Leduc, Mireille; Bon, Cassian; Gibbins, Jonathan M.

    2002-01-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130-kd transmembrane glycoprotein and a member of the growing family of receptors with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PECAM-1 is expressed on platelets, certain T cells, monocytes, neutrophils, and vascular endothelial cells and is involved in a range of cellular processes, though the role of PECAM-1 in platelets is unclear. Cross-linking of PECAM-1 results in phosphorylation of the ITIM allowing the r...

  20. Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial cell adhesion molecule 1.

    Lu, T T; Yan, L G; Madri, J. A.

    1996-01-01

    Platelet-endothelial cell adhesion molecule 1 (PECAM-1, CD31) is a 130-kDa member of the immunoglobulin gene superfamily expressed on endothelial cells, platelets, neutrophils, and monocytes and plays a role during endothelial cell migration. Phosphoamino acid analysis and Western blot analysis with anti-phosphotyrosine antibody show that endothelial PECAM-1 is tyrosine-phosphorylated. Phosphorylation is decreased with endothelial cell migration on fibronectin and collagen and with cell sprea...

  1. Effects of a healthy life exercise program on arteriosclerosis adhesion molecules in elderly obese women

    Lim, Seung-Taek; Min, Seok-Ki; Park, Hyuntae; Park, Jong-Hwan; Park, Jin-Kee

    2015-01-01

    [Purpose] The aim of this study was to investigate the change in the arteriosclerosis adhesion molecules after a healthy life exercise program that included aerobic training, anaerobic training, and traditional Korean dance. [Subjects] The subjects were 20 elderly women who were over 65 years of age and had 30% body fat. [Methods] The experimental group underwent a 12-week healthy life exercise program. To evaluate the effects of the healthy life exercise program, measurements were performed ...

  2. Levels of soluble adhesion molecules in patients with various clinical presentations of coronary atherosclerosis

    LU Hui-he; SHENG Zheng-qiang; WANG Yi; ZHANG Li

    2010-01-01

    Background Adhesion molecules play an important role in the development and progression of coronary atherosclerosis. The aim of this study was to compare concentrations of soluble forms of adhesion molecules in patients with different clinical presentations of coronary artery disease (CAD).Methods One hundred and twenty-eight patients with CAD were divided into three groups; the first group was acute myocardial infarction group (AMI group, n=45), the second group was unstable angina pectoris group (UAP group, n=48),the third group was stable angina pectoris group (SAP group, n=35). We compared them with patients with normal coronary arteries (control group, n=31). The serum levels of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were measured in all subjects.Results The serum level of VCAM-1 in the AMI group was significantly higher than in the UAP, SAP and control groups (P <0.01). The level in the UAP group was significantly higher than the SAP group and control group (P <0.01) and the level in the SAP group was significantly higher than in the control group (P <0.01). The serum ICAM-1 level was significantly elevated in the AMI, UAP and SAP groups as compared to the control group (P <0.01). The levels of serum E-selectin and P-selectin in the AMI and UAP groups were significantly higher than in the SAP and control groups (P<0.01).Conclusions Increased levels of VCAM-1 and ICAM-1, E-selectin and P-selectin, as markers of inflammation, showed the importance of inflammatory processes in the development of atherosclerosis and clinical expression of CAD. Soluble ICAM-1, VCAM-1, E-selectin and P-selectin concentrations are useful indicators of the presence of atherosclerosis and the severity of CAD clinical presentation.

  3. The cell adhesion molecule nectin-1 is critical for normal enamel formation in mice

    Barron, Martin J.; Brookes, Steven J.; Draper, Clare E.; Garrod, David; Kirkham, Jennifer; Shore, Roger C.; Dixon, Michael J

    2008-01-01

    Nectin-1 is a member of a sub-family of immunoglobulin-like adhesion molecules and a component of adherens junctions. In the current study, we have shown that mice lacking nectin-1 exhibit defective enamel formation in their incisor teeth. Although the incisors of nectin-1-null mice were hypomineralized, the protein composition of the enamel matrix was unaltered. While strong immunostaining for nectin-1 was observed at the interface between the maturation-stage ameloblasts and the underlying ...

  4. Adhesion Molecules, Altered Vasoreactivity, and Brain Atrophy in Type 2 Diabetes

    Novak, Vera; ZHAO, PENG; Manor, Brad; Sejdić, Ervin; Alsop, David; Abduljalil, Amir; Roberson, Paula K.; Munshi, Medha; Novak, Peter

    2011-01-01

    OBJECTIVE To investigate the effects of inflammation on perfusion regulation and brain volumes in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 147 subjects (71 diabetic and 76 nondiabetic, aged 65.2 ± 8 years) were studied using 3T anatomical and continuous arterial spin labeling magnetic resonance imaging. Analysis focused on the relationship between serum soluble vascular and intercellular adhesion molecules (sVCAM and sICAM, respectively, both markers of endothelial integrity), ...

  5. Red cell adhesion molecules, foetal haemoglobin and endothelial factors in sickle cell disorders

    Mundee, Y.

    2001-01-01

    Sickle cell anaemia (SS) is a haemoglobinopathy involving production of sickle haemoglobin (HbS, β⁶Glu-->Val), which is able to polymerise leading to vaso-occlusion. Hydroxyurea (HU) treatment increases foetal haemoglobin (HbF) levels but decreases vaso-occlusion and red cell adhesion molecule (AM) expression, and therefore improves clinical symptoms. In this thesis, the contribution of AMs, HbF and endothelial factors to the severity of sickle cell disease has been studied....

  6. Cellular Adhesion Molecules in Healthy Subjects: Short Term Variations and Relations to Flow Mediated Dilation

    Claus Dethlefsen

    2008-01-01

    Full Text Available The objective was primarily to describe short term intra-individual variation in serum levels of soluble adhesion molecules (sCAMs: E-selectin, P-selectin, intercellular adhesion molecule-1(sICAM-1 and vascular cellular adhesion molecule-1(sVCAM-1 in healthy subjects. Secondly, sCAMs were correlated to brachial artery fl ow mediated vasodilation (FMD.Forty healthy subjects aged 24–66 years had sCAMs measured twice with 4 week intervals and short-term intra-individual variation was estimated as variation in the paired measurements after correcting for the analytical precision of the used method. At baseline, brachial FMD was measured. No difference was observed in mean sCAMs in the whole study group. Estimated intra-subject variations in sCAMs were 7.6–11.3%. In a regression analysis, significant negative association was found between sE-selectin and FMD after controlling for possible confounders (p < 0.04 while no significant correlation could be demonstrated between the other sCAMs and FMD.In conclusion, short term intra-individual variations in sCAMs were 7.6–11.3% in healthy subjects. We also found a significant negative association between sE-selectin and FMD, indicating an possible association between inflammation and dysfunction of the vascular endothelium; however further studies are required to confirm this preliminary finding.

  7. Role of adhesion molecules and inflammation in Venezuelan equine encephalitis virus infected mouse brain

    Honnold Shelley P

    2011-04-01

    Full Text Available Abstract Background Neuroinvasion of Venezuelan equine encephalitis virus (VEEV and subsequent initiation of inflammation in the brain plays a crucial role in the outcome of VEEV infection in mice. Adhesion molecules expressed on microvascular endothelial cells in the brain have been implicated in the modulation of the blood brain barrier (BBB and inflammation in brain but their role in VEEV pathogenesis is not very well understood. In this study, we evaluated the expression of extracellular matrix and adhesion molecules genes in the brain of VEEV infected mice. Findings Several cell to cell adhesion molecules and extracellular matrix protein genes such as ICAM-1, VCAM-1, CD44, Cadherins, integrins, MMPs and Timp1 were differentially regulated post-VEEV infection. ICAM-1 knock-out (IKO mice infected with VEEV had markedly reduced inflammation in the brain and demonstrated a delay in the onset of clinical symptoms of disease. A differential regulation of inflammatory genes was observed in the IKO mice brain compared to their WT counterparts. Conclusions These results improve our present understanding of VEEV induced inflammation in mouse brain.

  8. The neural adhesion molecule TAG-1 modulates responses of sensory axons to diffusible guidance signals.

    Law, Chris O; Kirby, Rebecca J; Aghamohammadzadeh, Soheil; Furley, Andrew J W

    2008-08-01

    When the axons of primary sensory neurons project into the embryonic mammalian spinal cord, they bifurcate and extend rostrocaudally before sending collaterals to specific laminae according to neuronal subclass. The specificity of this innervation has been suggested to be the result both of differential sensitivity to chemorepellants expressed in the ventral spinal cord and of the function of Ig-like neural cell adhesion molecules in the dorsal horn. The relationship between these mechanisms has not been addressed. Focussing on the pathfinding of TrkA+ NGF-dependent axons, we demonstrate for the first time that their axons project prematurely into the dorsal horn of both L1 and TAG-1 knockout mice. We show that axons lacking TAG-1, similar to those lacking L1, are insensitive to wild-type ventral spinal cord (VSC)-derived chemorepellants, indicating that adhesion molecule function is required in the axons, and that this loss of response is explained in part by loss of response to Sema3A. We present evidence that TAG-1 affects sensitivity to Sema3A by binding to L1 and modulating the endocytosis of the L1/neuropilin 1 Sema3A receptor complex. However, TAG-1 appears to affect sensitivity to other VSC-derived chemorepellants via an L1-independent mechanism. We suggest that this dependence of chemorepellant sensitivity on the functions of combinations of adhesion molecules is important to ensure that axons project via specific pathways before extending to their final targets. PMID:18550718

  9. Evaluation of C-Reactive Protein, Endothelin-1, Adhesion Molecule(s), and Lipids as Inflammatory Markers in Type 2 Diabetes Mellitus Patients

    2007-01-01

    This study compared lipids, the product of lipid peroxidation malondialdehyde (MDA), the acute phase reactant high-sensitive C-reactive protein (hsCRP), endothelin-1 (ET-1), P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) between healthy controls, subjects with ischemic heart disease (IHD) and type 2 diabetes mellitus (DM) subjects who did not perform coronary artery bypass graft (CABG) surgery as well as type 2 DM subjects who performed ...

  10. Propofol protects against high glucose-induced endothelial adhesion molecules expression in human umbilical vein endothelial cells

    Zhu Minmin

    2013-01-01

    Full Text Available Abstract Background Hyperglycemia could induce oxidative stress, activate transcription factor nuclear factor kappa B (NF-κB, up-regulate expression of endothelial adhesion molecules, and lead to endothelial injury. Studies have indicated that propofol could attenuate oxidative stress and suppress NF-κB activation in some situations. In the present study, we examined whether and how propofol improved high glucose-induced up-regulation of endothelial adhesion molecules in human umbilical vein endothelial cells (HUVECs. Methods Protein expression of endothelial adhesion molecules, NF-κB, inhibitory subunit of NF-κBα (IκBα, protein kinase Cβ2 (PKCβ2, and phosphorylation of PKCβ2 (Ser660 were measured by Western blot. NF-κB activity was measured by electrophoretic mobility shift assay. PKC activity was measured with SignaTECT PKC assay system. Superoxide anion (O2.- accumulation was measured with the reduction of ferricytochrome c assay. Human peripheral mononuclear cells were prepared with Histopaque-1077 solution. Results High glucose induced the expression of endothelial selectin (E-selectin, intercellular adhesion molecule 1 (ICAM-1, vascular cell adhesion molecule 1 (VCAM-1, and increased mononuclear-endothelial adhesion. High glucose induced O2.- accumulation, PKCβ2 phosphorylation and PKC activation. Further, high glucose decreased IκBα expression in cytoplasm, increased the translocation of NF-κB from cytoplasm to nuclear, and induced NF-κB activation. Importantly, we found these high glucose-mediated effects were attenuated by propofol pretreatment. Moreover, CGP53353, a selective PKCβ2 inhibitor, decreased high glucose-induced NF-κB activation, adhesion molecules expression, and mononuclear-endothelial adhesion. Conclusion Propofol, via decreasing O2.- accumulation, down-regulating PKCβ2 Ser660 phosphorylation and PKC as well as NF-κB activity, attenuated high glucose-induced endothelial adhesion molecules expression

  11. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  12. Nuclear factor kappaB-mediated down-regulation of adhesion molecules: possible mechanism for inhibitory activity of bigelovin against inflammatory monocytes adhesion to endothelial cells.

    Nam, Kung-Woo; Oh, Goo Taeg; Seo, Eun-Kyoung; Kim, Kyeong Ho; Koo, Uk; Lee, Sung-Jin; Mar, Woongchon

    2009-06-22

    The flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae) are used in traditional medicine to treat asthma, chronic bronchitis, and acute pleurisy in China and Korea. However, the pharmacological actions of Inula britannica L. var. chinensis on endothelial cells and inflammatory monocytes are not clear. In this study, we investigated whether bigelovin, a sesquiterpene lactone isolated from the flowers of Inula britannica L. var. chinensis, inhibits monocyte adhesion and adhesion molecule expression in brain endothelial cells. We measured tumor necrosis factor-alpha (TNF-alpha)-enhanced Raw264.7 monocyte binding to brain endothelial cells and the levels of cell adhesion molecules, including vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and endothelial-selectin (E-selectin) on the surface of brain endothelial cells. Bigelovin significantly inhibited these in a dose-dependent manner without affecting cell viability. Furthermore, bigelovin suppressed the nuclear factor kappaB (NF-kappaB) promoter-driven luciferase activity, NF-kappaB activation, and degradation of NF-kappaB inhibitor protein alpha (IkappaBalpha). These results indicate that bigelovin inhibits inflammatory monocyte adhesion to endothelial cells and the expression of VCAM-1, ICAM-1, and E-selectin by blocking IkappaBalpha degradation and NF-kappaB activation. PMID:19429369

  13. Gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells during sepsis

    吴荣谦; 徐迎新; 宋旭华; 孟宪钧

    2002-01-01

    To study the gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells during sepsis in mice. Methods: Male mice were subjected to cecal ligation and puncture (CLP) and microvascular endothelial cells in pulmonary and hepatic tissues were harvested at 3 hours (early sepsis) and 12 hours (late sepsis) after CLP, respectively. Gene expression of the adhesion molecules was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the alterations of myeloperoxidase (MPO) activity in pulmonary and hepatic tissues were also examined. Results: E-selectin mRNA levels markedly increased at 3 hours after CLP in both pulmonary and hepatic microvascular endothelial cells, then they returned to the normal level at 12 hours after CLP. Increases in intercellular adhesion molecule-1 (ICAM-1) mRNA levels were found at 3 hours after CLP in both pulmonary and hepatic microvascular endothelial cells, and these levels became higher at 12 hours after CLP. Adhesion molecule-1 (VCAM-1) mRNA expression of vascular cells also increased significantly at 3 hours and 12 hours after CLP in both pulmonary and hepatic microvascular endothelial cells. The level of VCAM-1 mRNA in hepatic microvascular endothelial cells was higher at 3 hours than that at 12 hours after CLP, while the level of VCAM-1 mRNA in pulmonary microvascular endothelial cells was higher at 12 hours than that at 3 hours after CLP. The MPO activity in pulmonary and hepatic tissues increased at 3 hours after CLP, compared with that of the sham group. They both declined significantly at 12 hours after CLP, but they were still higher than that of the sham group. Conclusions: The up-regulation of the gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells is an important step for the migration and accumulation of leukocytes at the site of inflammation, which plays a critical role in organ damage during sepsis. And the contribution

  14. Regulation of N-CAM and ganglioside expression in neuroblastoma x glioma hybrid, NG108-15, cells

    A monoclonal antibody (Mab) that recognizes the neural cell-adhesion sialoglycoprotein, N-CAM, and another Mab, A2B5, that recognizes a family of gangliosides were used to study the regulation of their expression in NG108-15 cells. Radioimmunoassay of membrane fractions or analysis of western blots of solubilized proteins with 125I-labelled antibodies was performed. Retinoic acid (1.6 μM: 48 hr) and the potent tumor promoter, PMA (0.16 μM: 48 hr), were found to elevate N-CAM and ganglioside levels 2-3 fold over controls. Under the same conditions, phorbol alone had no effect but dibutyrl-cyclic AMP (1 mM) was found to inhibit N-CAM expression (by 50%) but stimulate A2B5 binding 2-fold. When NG108-15 cells were cocultured with fetal rat muscle, muscle conditioned medium or in the presence of exudates from muscle cultures, marked effects on the expression of the different molecular weight forms of N-CAM were observed. These results further support the idea that cell surface sialoglycoconjugate expression is under complex control, perhaps involving the regulation of glycosyltransferases by cyclic-AMP-dependent protein kinase and protein kinase C

  15. Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

  16. Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

    Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T. [Department of Kinesiology, The University of Toledo, Toledo, OH (United States); Pierre, Philippe [Centre d’Immunologie de Marseille-Luminy U2M, Aix-Marseille Université, Marseille (France); INSERM U631, Institut National de la Santé et Recherche Médicale, Marseille (France); CNRS UMR6102, Centre National de la Recherche Scientifique, Marseille (France); Chadee, Deborah N. [Department of Biological Sciences, The University of Toledo, Toledo, OH (United States); Pizza, Francis X., E-mail: Francis.Pizza@utoledo.edu [Department of Kinesiology, The University of Toledo, Toledo, OH (United States)

    2015-02-15

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

  17. The cell adhesion molecules Echinoid and Friend of Echinoid coordinate cell adhesion and cell signaling to regulate the fidelity of ommatidial rotation in the Drosophila eye

    Fetting, Jennifer L.; Spencer, Susan A; Wolff, Tanya

    2009-01-01

    Directed cellular movements are a universal feature of morphogenesis in multicellular organisms. Differential adhesion between the stationary and motile cells promotes these cellular movements to effect spatial patterning of cells. A prominent feature of Drosophila eye development is the 90° rotational movement of the multicellular ommatidial precursors within a matrix of stationary cells. We demonstrate that the cell adhesion molecules Echinoid (Ed) and Friend of Echi...

  18. Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo

    Joussen, Antonia M; Poulaki, Vassiliki; Qin, Wenying; Kirchhof, Bernd; Mitsiades, Nicholas; Wiegand, Stanley J; Rudge, John; George D. Yancopoulos; Adamis, Anthony P.

    2002-01-01

    Leukocyte adhesion to the diabetic retinal vasculature results in early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM-1) and CD18 are required for these processes. However the relevant in vivo stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current study investigated the causal role of endogenous vascular endothelial growth factor (VEGF) and nitric oxid...

  19. Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery

    Toft, P; Christiansen, K; Tønnesen, Else Kirstine;

    1997-01-01

    Following cardiac surgery with cardiopulmonary bypass (CPB), activated granulocytes may be involved with ischaemia/ reperfusion injury. The purpose of this study was to investigate whether steroids could reduce the oxidative burst activity of granulocytes, the expression of adhesion molecules on...... cytometrically using 123-dihydrorhodamine. A panel of adhesion molecules was measured using monoclonal antibodies. Following CPB the oxidative burst activity and the expression of the adhesion molecule L-selectin more than doubled compared to initial values. There was no difference between the steroid group and...... the control group regarding the expression of adhesion molecules or the oxidative burst activity. In the steroid group the fluid gain during extracorporeal circulation (ECC) was 683 ml (median) compared to 1488 ml in the control group. Steroids prevented hyperthermia in the postoperative period but...

  20. Neutrophil surface adhesion molecule and toll like receptor dynamics in crossbred cows suffering from Staphylococcus aureus subclinical and clinical mastitis

    Dilip Kumar Swain

    2016-06-01

    Conclusion: Host elicits stage specific expression of surface adhesion molecules and TLR2 and TLR4 as dynamic host innate immune response against Staphylococcal mastitis. [J Adv Vet Anim Res 2016; 3(2.000: 99-105

  1. Depletion of water molecules during ethanol wet-bonding with etch and rinse dental adhesives

    The treatment of demineralized dentin with ethanol has been proposed as a way to improve hydrophobic monomer penetration into otherwise water saturated collagen fibrils. The ethanol rinse is expected to preserve the fibrils from collapsing while optimizing resin constituent infiltration for better long term adhesion. The physico-chemical investigations of demineralized dentin confirmed objectively these working hypotheses. Namely, Differential Scanning Calorimetry (DSC) measurements of the melting point of water molecules pointed to the presence of free and bound water states. Unfreezable water was the main type of water remaining following a rinsing step with absolute ethanol. Two different liquid water phases were also observed by Magic Angle Spinning (MAS) solid state Nuclear magnetic Resonance (NMR) spectroscopy. Infrared spectra of ethanol treated specimens illustrated differences with the fully hydrated specimens concerning the polar carbonyl vibrations. Optical microscopy observations as well as scanning electron microscopy showed an improved dentin-adhesive interface with ethanol wet bonding. The results indicate that water can be confined to strongly bound structural molecules when excess water is removed with ethanol prior to adhesive application. This should preserve collagen from hydrolysis upon aging of the hybrid layer. - Highlights: ► Non-freezable water exists in demineralized dentine. ► Free water can be removed by ethanol rinse of the demineralized collagen. ► Ethanol wet bonding leads to a homogeneous hybrid layer free of defects.

  2. Depletion of water molecules during ethanol wet-bonding with etch and rinse dental adhesives

    Gregoire, Genevieve, E-mail: gregoire@cict.fr [Department of Biomaterials, Faculty of Odontology, University Toulouse III, 31062, Toulouse (France); Sharrock, Patrick [Medical and Spatial Imaging Laboratory, University Toulouse III, Ave. Pompidou, 81104, Castres (France); Delannee, Mathieu [Department of Biomaterials, Faculty of Odontology, University Toulouse III, 31062, Toulouse (France); Delisle, Marie-Bernadette [Faculty of Medicine, University Toulouse III, 31062, Toulouse (France)

    2013-01-01

    The treatment of demineralized dentin with ethanol has been proposed as a way to improve hydrophobic monomer penetration into otherwise water saturated collagen fibrils. The ethanol rinse is expected to preserve the fibrils from collapsing while optimizing resin constituent infiltration for better long term adhesion. The physico-chemical investigations of demineralized dentin confirmed objectively these working hypotheses. Namely, Differential Scanning Calorimetry (DSC) measurements of the melting point of water molecules pointed to the presence of free and bound water states. Unfreezable water was the main type of water remaining following a rinsing step with absolute ethanol. Two different liquid water phases were also observed by Magic Angle Spinning (MAS) solid state Nuclear magnetic Resonance (NMR) spectroscopy. Infrared spectra of ethanol treated specimens illustrated differences with the fully hydrated specimens concerning the polar carbonyl vibrations. Optical microscopy observations as well as scanning electron microscopy showed an improved dentin-adhesive interface with ethanol wet bonding. The results indicate that water can be confined to strongly bound structural molecules when excess water is removed with ethanol prior to adhesive application. This should preserve collagen from hydrolysis upon aging of the hybrid layer. - Highlights: Black-Right-Pointing-Pointer Non-freezable water exists in demineralized dentine. Black-Right-Pointing-Pointer Free water can be removed by ethanol rinse of the demineralized collagen. Black-Right-Pointing-Pointer Ethanol wet bonding leads to a homogeneous hybrid layer free of defects.

  3. Mice lacking the synaptic adhesion molecule Neph2/Kirrel3 display moderate hyperactivity and defective novel object preference

    Su Yeon eChoi; Kihoon eHan; Tyler eCutforth; Woosuk eChung; Haram ePark; Dongsoo eLee; Ryunhee eKim; Myeong-Heui eKim; Yeeun eChoi; Kang eShen; Eunjoon eKim

    2015-01-01

    Synaptic adhesion molecules regulate diverse aspects of neuronal synapse development, including synapse specificity, formation, and maturation. Neph2, also known as Kirrel3, is an immunoglobulin superfamily adhesion molecule implicated in intellectual disability, neurocognitive delay associated with Jacobsen syndrome, and autism spectrum disorders. We here report mice lacking Neph2 (Neph2-/- mice) display moderate hyperactivity in a familiar, but not novel, environment and defective novel obj...

  4. Tauopathy Differentially Affects Cell Adhesion Molecules in Mouse Brain: Early Down-Regulation of Nectin-3 in Stratum Lacunosum Moleculare

    Hervé Maurin; Claire Marie Seymour; Benoit Lechat; Peter Borghgraef; Herman Devijver; Tomasz Jaworski; Schmidt, Mathias V.; Sebastian Kuegler; Fred Van Leuven

    2013-01-01

    Cell adhesion molecules are important structural substrates, required for synaptic plasticity and synaptogenesis. CAMs differ widely in their expression throughout different brain regions and their specific structural and functional roles in the brain remain to be elucidated. Here, we investigated selected cell adhesion molecules for alterations in expression levels and neuronal localization in validated mouse models for Alzheimer's disease that mimic the age-related progression of amyloid ac...

  5. The carbon monoxide releasing molecule (CORM-3) inhibits expression of vascular cell adhesion molecule-1 and E-selectin independently of haem oxygenase-1 expression

    Song, H.; Bergstrasser, C.; Rafat, N.; Hoeger, S.; Schmidt, M.; Endres, N.; Goebeler, M.; Hillebrands, J. L.; Brigelius-Flohe, R.; Banning, A.; Beck, G.; Loesel, R.; Yard, B. A.

    2009-01-01

    Background and purpose: Although carbon monoxide (CO) can modulate inflammatory processes, the influence of CO on adhesion molecules is less clear. This might be due to the limited amount of CO generated by haem degradation. We therefore tested the ability of a CO releasing molecule (CORM-3), used i

  6. Neutrophil transmigration under shear flow conditions in vitro is junctional adhesion molecule-C independent.

    Sircar, Monica; Bradfield, Paul F; Aurrand-Lions, Michel; Fish, Richard J; Alcaide, Pilar; Yang, Lin; Newton, Gail; Lamont, Deanna; Sehrawat, Seema; Mayadas, Tanya; Liang, Tony W; Parkos, Charles A; Imhof, Beat A; Luscinskas, Francis W

    2007-05-01

    Endothelial cell junctional adhesion molecule (JAM)-C has been proposed to regulate neutrophil migration. In the current study, we used function-blocking mAbs against human JAM-C to determine its role in human leukocyte adhesion and transendothelial cell migration under flow conditions. JAM-C surface expression in HUVEC was uniformly low, and treatment with inflammatory cytokines TNF-alpha, IL-1beta, or LPS did not increase its surface expression as assessed by FACS analysis. By immunofluorescence microscopy, JAM-C staining showed sparse localization to cell-cell junctions on resting or cytokine-activated HUVEC. Surprisingly, staining of detergent-permeabilized HUVEC revealed a large intracellular pool of JAM-C that showed little colocalization with von Willebrand factor. Adhesion studies in an in vitro flow model showed that functional blocking JAM-C mAb alone had no inhibitory effect on polymorphonuclear leukocyte (PMN) adhesion or transmigration, whereas mAb to ICAM-1 significantly reduced transmigration. Interestingly, JAM-C-blocking mAbs synergized with a combination of PECAM-1, ICAM-1, and CD99-blocking mAbs to inhibit PMN transmigration. Overexpression of JAM-C by infection with a lentivirus JAM-C GFP fusion protein did not increase adhesion or extent of transmigration of PMN or evoke a role for JAM-C in transendothelial migration. These data suggest that JAM-C has a minimal role, if any, in PMN transmigration in this model and that ICAM-1 is the preferred endothelial-expressed ligand for PMN beta(2) integrins during transendothelial migration. PMID:17442972

  7. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array

    Bekő Gabriella

    2010-12-01

    Full Text Available Abstract Background Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive arms of the immune system. Cytokines, chemokines and adhesion molecules are central to innate and adaptive immune processes. The purpose of this study was to determine circulating levels of cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia in a comprehensive manner, and to investigate their relationship to the clinical features and laboratory parameters of the study participants, including markers of overall inflammation (C-reactive protein, endothelial activation (von Willebrand factor antigen and endothelial injury (fibronectin, oxidative stress (malondialdehyde and trophoblast debris (cell-free fetal DNA. Results Serum levels of interleukin (IL-1beta, IL-1 receptor antagonist (IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, transforming growth factor (TGF-beta1, interferon-gamma-inducible protein (IP-10, monocyte chemotactic protein (MCP-1, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 were measured in 60 preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by multiplex suspension array and ELISA. In normal pregnancy, the relative abundance of circulating IL-18 over IL-12p70 and the relative deficiency of the bioactive IL-12p70 in relation to IL-12p40 might favour Th2-type immunity. Although decreased IL-1ra, TNF-alpha and MCP-1 concentrations of healthy pregnant relative to non-pregnant women reflect anti-inflammatory changes in circulating cytokine profile, their decreased serum IL-10 and increased IP-10 levels might drive pro-inflammatory responses. In addition to a shift towards Th1-type immunity (expressed by the increased IL-2/IL-4 and IFN-gamma/IL-4 ratios, circulating levels of

  8. Cytoskeletal inhibitors, anti-adhesion molecule antibodies, and lectins inhibit hepatocyte spheroid formation.

    Nakamura M

    2002-02-01

    Full Text Available We investigated the role of cytoskeletons, adhesion molecules, membrane-glycosylations, and proteoglycans in forming the shape of adult rat hepatocyte spheroids. Isolated hepatocytes were cultured on dishes coated with chondroitin sulfate phosphatidyl ethanolamine (CS-PE. Spheroid-forming ability was observed after adding cytoskeletal inhibitors (cytochalasin D, colchicine, okadaic acid, mycalolide B, anti-adhesion molecule antibodies (anti-E-cadherin, anti-connexin 32, anti-zo-1, a glycosphingolipid synthetic inhibitor (N-butyldeoxynojirimycin, a proteoglycan synthetic inhibitor (p-nitrophenyl-beta-D-xylopyranoside, and several lectins. Localization of actin was studied using confocal microscopy after rhodamine-phalloidin staining. Adding cytoskeletal inhibitors on the initial day resulted in weakly clustered cell aggregates rather than smoothly formed spheroids. These effects disappeared at lower reagent concentrations. When reagents were added on day 3, after the formation of spheroids, only mycalolide B was associated with an irregular spheroid surface; the others had no effect. Adding the anti-E-cadherin, anti-connexin 32 on the initial day showed inhibition of spheroid formation, but anti-zo-1 and proteoglycan synthetic inhibitor had no effects. Among the several lectins, only Wheat Germ Agglutinin (WGA, Ricinus communis Agglutinin I (RCA-I, and Concanavalin A (ConA showed inhibition. These results suggest that cytoskeletal conformation and some adhesion molecules are necessary to form spheroids. Based on the interactions between lectins and hepatocytes in the present study, hepatocytes appear to contain an N-linked complex or N-linked hybrid glycosylated chains.

  9. Serum Soluble Intercellular Adhesion Molecule-1 Level in Acute Lymphoblastic Leukemia in Children

    Impaired migration of leucocytes is a characteristic feature of leukemia. Knowledge of the mechanisms of leukemic cells migration has expanded greatly in recent years. Leukocyte infiltrates are formed in surrounding tissues due to changes in chemokines and adhesion molecules concentrations. The present study included 45 patients with acute lymphoblastic leukemia (ALL). The mean of their ages was 6.10±4.39 years. They were 29 males and 16 females. They were chosen from those attending the Oncology Clinic and inpatient wards of the National Cancer Institute, Cairo University. They were classified into 3 groups according to the disease activity: Group I: Comprised 15 newly diagnosed cases of ALL. Group II: Consisted of 15 cases of ALL during relapse period. Group III included 15 cases of ALL during complete remission. Also, 15 apparently healthy children with matched age and sex as a control group (group IV). All the studied cases were subjected to thorough clinical examination as well as the following investigations: complete blood picture, bone marrow biopsy and estimation of serum intercellular adhesion molecule-1 (sICAM-1) by ELISA.The results of this study revealed that serum ICAM-l showed no significant changes in its value on comparing group I (newly diagnosed cases) and group II (cases during relapse). On the other hand, a significant higher level of sICAM-1 was observed on comparing groups I and II with group III (cases during remission) separately (P0.05).From this it was concluded that the levels of serum soluble intercellular circulating adhesion molecule ICAM-1 can be utilized for monitoring disease activity of ALL and its response to treatment, as well as for early detection of relapse.

  10. Intercellular Adhesion Molecule 1 Promotes HIV-1 Attachment but Not Fusion to Target Cells

    Naoyuki Kondo; Melikyan, Gregory B.

    2012-01-01

    Incorporation of intercellular adhesion molecule 1 (ICAM-1) into HIV-1 particles is known to markedly enhance the virus binding and infection of cells expressing lymphocyte function-associated antigen-1 (LFA-1). At the same time, ICAM-1 has been reported to exert a less pronounced effect on HIV-1 fusion with lymphoid cells. Here we examined the role of ICAM-1/LFA-1 interactions in productive HIV-1 entry into lymphoid cells using a direct virus-cell fusion assay. ICAM-1 promoted HIV-1 attachme...

  11. Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis

    Okuda, Ryo; Matsushima, Hidekazu; Aoshiba, Kazutetsu; Oba, Tomohiro; Kawabe, Rie; Honda, Koujiro; Amano, Masako

    2015-01-01

    The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other inte...

  12. Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

    Edwards, B D; Andrew, S M; O'Driscoll, J B; Chalmers, R J; Ballardie, F W; Freemont, A J

    1993-01-01

    AIM--To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules. METHODS--Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin. Biopsy specimens taken from skin before, during, and after cyclosporin treatment were stained immunohistochemically for CD 54 (ICAM-1), CD 29 (beta-1 integrins), and CD18 (beta-2 integrins). RESULTS--There was a highly significant (p < 0.01) c...

  13. Neuron-glia cell adhesion molecule interacts with neurons and astroglia via different binding mechanisms

    1988-01-01

    The neuron-glia cell adhesion molecule (Ng-CAM) is present in the central nervous system on postmitotic neurons and in the periphery on neurons and Schwann cells. It has been implicated in binding between neurons and between neurons and glia. To understand the molecular mechanisms of Ng-CAM binding, we analyzed the aggregation of chick Ng- CAM either immobilized on 0.5-micron beads (Covaspheres) or reconstituted into liposomes. The results were correlated with the binding of these particles t...

  14. Linear organization of the liver cell adhesion molecule L-CAM.

    Cunningham, B A; Leutzinger, Y; Gallin, W J; Sorkin, B C; Edelman, G M

    1984-01-01

    A linear model of the liver cell adhesion molecule L-CAM from embryonic chickens is proposed in terms of its orientation on the cell surface, the number, type, and distribution of carbohydrate moieties, and sites of phosphorylation. L-CAM is isolated from cell membranes as a glycoprotein of Mr = 124,000. A soluble fragment (Ft1) of Mr = 81,000 can be released from cells by digestion with trypsin in the presence of calcium. Radiochemical amino acid sequence analyses indicated that both polypep...

  15. A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

    Damotte, V; Guillot-Noel, L; Patsopoulos, N A; Madireddy, L; El Behi, M; De Jager, P L; Baranzini, S E; Cournu-Rebeix, I; Fontaine, B; Sørensen, Per Soelberg

    2014-01-01

    interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell...... adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes...

  16. Environmental impacts on the developing CNS: CD15, NCAM-L1, and GFAP expression in rat neonates exposed to hypergravity

    Sulkowski, G. M.; Li, G.-H.; Sajdel-Sulkowska, E. M.

    2004-01-01

    We have previously reported that the developing rat cerebellum is affected by hypergravity exposure. The effect is observed during a period of both granule and glial cell proliferation and neuronal migration in the cerebellum and coincides with changes in thyroid hormone levels. The present study begins to address the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of cerebellar proteins that are known to be directly involved in cell-cell interactions [protein expressing 3-fucosyl- N-acetyl-lactosamine antigen (CD15), neuronal cell adhesion molecule (NCAM-L1)] and those that affect cell-cell interactions indirectly [glial fibrillary acidic protein (GFAP)] in rat neonates exposed to centrifuge-produced hypergravity. Cerebellar mass and protein expression in rat neonates exposed to hypergravity (1.5 G) from gestational day (G) 11 to postnatal day (P) 30 were compared at one of six time points between P6 and P30 against rat neonates developing under normal gravity. Proteins were analyzed by quantitative western blots of cerebellar homogenates prepared from male or female neonates. Cerebellar size was most clearly reduced in male neonates on P6 and in female neonates on P9, with a significant gender difference; differences in cerebellar mass remained significant even when change in total body mass was factored in. Densitometric analysis of western blots revealed both quantitative and temporal changes in the expression of selected cerebellar proteins that coincided with changes in cerebellar mass and were gender-specific. In fact, our data indicated certain significant differences even between male and female control animals. A maximal decrease in expression of CD15 was observed in HG females on P9, coinciding with maximal change in their cerebellar mass. A shift in the time-course of NCAM-L1 expression resulted in a significant increase in NCAM-L1 in HG males on P18, an isolated time at which

  17. Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression.

    Masato Murakami

    Full Text Available Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A-/- tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target.

  18. Cytokines and adhesion molecules in multiple sclerosis patients treated with interferon-beta1b

    Jensen, Jakob; Krakauer, Martin; Sellebjerg, Finn

    2005-01-01

    Multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS), is thought to be caused by a T cell-mediated attack on CNS myelin and axons. Recombinant interferon (IFN)-beta is an established treatment of multiple sclerosis, and is known to reduce the number of...... disease relapses and the development of irreversible symptoms and signs of disease. The mechanism of action of IFN-beta treatment is, however, not completely understood. Previous studies have suggested major effects on mononuclear cell cytokine production and T cell migration, but results have been...... inconsistent. We found decreases in CD4 and CD8 T cell expression of the CD49d/VLA-4 molecule, increases in plasma concentrations of soluble vascular cell adhesion molecule (sVCAM-1), and increases in plasma concentrations of tumor necrosis factor and interleukin (IL)-12 p40 chain in patients with MS who were...

  19. Influence of dose-rate on inflammatory damage and adhesion molecule expression after abdominal radiation in the rat

    Purpose: The goal of this study was to assess the effects of two clinically relevant radiation dose-rates on endothelial adhesion molecule expression, inflammatory response, and microvascular dysfunction. Methods and Materials: Rats were irradiated with 10 Gy at low (0.9 Gy/min) or high (3 Gy/min) dose-rates. Control animals received sham irradiation. Leukocyte rolling, adhesion, emigration, and microvascular permeability were assessed in mesenteric venules by intravital microscopy 6 hours after irradiation. P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression were measured using radiolabeled monoclonal antibodies. Results: Low dose-rate (LDR) abdominal irradiation increased leukocyte adhesion compared with sham-irradiated animals, whereas high dose-rate (HDR) irradiation resulted in enhanced leukocyte rolling, adhesion, and emigration, compared with the LDR or with sham-irradiated rats. Both dose-rates increased microvascular permeability, although this effect was significantly greater after radiation with the high (8-fold) than the low (5-fold) dose-rate. HDR radiation induced significantly larger increments in P-selectin expression in splanchnic organs than LDR, whereas in most organs ICAM-1 expression was only upregulated by the HDR. Blockade of ICAM-1, but not P-selectin, abrogated leukocyte adhesion at both dose-rates. Conclusions: The magnitude of upregulation of endothelial adhesion molecules, leukocyte recruitment, and endothelial barrier dysfunction elicited by radiation therapy is dependent on the dose-rate at which the radiation is delivered

  20. Effect of Cell Adhesion Molecule 1 Expression on Intracellular Granule Movement in Pancreatic α Cells.

    Yokawa, Satoru; Furuno, Tadahide; Suzuki, Takahiro; Inoh, Yoshikazu; Suzuki, Ryo; Hirashima, Naohide

    2016-09-01

    Although glucagon secreted from pancreatic α cells plays a role in increasing glucose concentrations in serum, the mechanism regulating glucagon secretion from α cells remains unclear. Cell adhesion molecule 1 (CADM1), identified as an adhesion molecule in α cells, has been reported not only to communicate among α cells and between nerve fibers, but also to prevent excessive glucagon secretion from α cells. Here, we investigated the effect of CADM1 expression on the movement of intracellular secretory granules in α cells because the granule transport is an important step in secretion. Spinning disk microscopic analysis showed that granules moved at a mean velocity of 0.236 ± 0.010 μm/s in the mouse α cell line αTC6 that expressed CADM1 endogenously. The mean velocity was significantly decreased in CADM1-knockdown (KD) cells (mean velocity: 0.190 ± 0.016 μm/s). The velocity of granule movement decreased greatly in αTC6 cells treated with the microtubule-depolymerizing reagent nocodazole, but not in αTC6 cells treated with the actin-depolymerizing reagent cytochalasin D. No difference in the mean velocity was observed between αTC6 and CADM1-KD cells treated with nocodazole. These results suggest that intracellular granules in pancreatic α cells move along the microtubule network, and that CADM1 influences their velocity. PMID:27262873

  1. Association of adipokines and adhesion molecules with indicators of obesity in women undergoing mammography screening

    Isoppo de Souza Caroline

    2012-10-01

    Full Text Available Abstract Background The soluble cell adhesion molecules and adipokines are elevated in patients with obesity, hypertension, type 2 diabetes mellitus, breast cancer and atherosclerosis. Objective To investigate the relationship between anthropometric profile, dietary intake, lipid profile and fasting glycemia with serum levels of adipokines (adiponectin and PAI-1 and adhesion molecules (ICAM-1 and VCAM-1 in women without breast cancer undergoing routine mammographic screening. Design Transversal study. Subjects One hundred and forty-five women over 40-years old participated in this study. Results In 39.3% of cases the BMI was above 30 kg/m2; 46.9% had hypertension, 14.5% had type 2 Diabetes Mellitus, 31.7% had dyslipidemia and 88.3% presented a waist-to-hip ratio ≥ 0.8. A linear correlation was found between serum levels of PAI-1 and triglycerides, between serum levels of PAI-1 and WHR and between serum levels of VCAM-1 and BMI. Conclusion We found a high prevalence of obesity and metabolic syndrome. PAI-1 and VCAM-1 levels were correlated with clinical indicators of obesity and overweight.

  2. Antithrombin can modulate coagulation, cytokine production, and expression of adhesion molecules in abdominal aortic aneurysm repair surgery.

    Nishiyama, Tomoki

    2006-04-01

    We investigated the effects of antithrombin on coagulation, fibrinolysis, and production of cytokines and adhesion molecules in abdominal aortic aneurysm repair surgery. Sixteen patients for Y-shaped graft replacement of abdominal aortic aneurysm were divided into an antithrombin group and a control group. In the antithrombin group, 3000 U antithrombin was infused over 30 min before heparin administration and 24 h later. White blood cell counts, platelet counts, prothrombin time ratio, and serum concentrations of antithrombin, polymorphonuclear leukocyte elastase, interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and adhesion molecules, and variables of coagulation and fibrinolysis were measured before surgery, at the end of surgery, and 1 and 2 days after surgery. The antithrombin concentration decreased in the control group, whereas it increased in the antithrombin group with significant differences between the groups. Prothrombin time ratio, concentrations of d-dimer, thrombin-antithrombin complex, and intercellular adhesion molecule-1 increased only in the control group and polymorphonuclear leukocyte elastase, IL-6, tumor necrosis factor-alpha, and vascular cell adhesion molecule-1 increased in both groups. They were significantly less in the antithrombin group except for intercellular adhesion molecule-1. In conclusion, antithrombin could decrease hypercoagulation and inflammatory activation during abdominal aortic aneurysm surgery, which may decrease adverse events. PMID:16551889

  3. Alcohol inhibits cell-cell adhesion mediated by human L1.

    Ramanathan, R; Wilkemeyer, M F; Mittal, B; Perides, G; Charness, M E

    1996-04-01

    Mental retardation, hydrocephalus, and agenesis of the corpus callosum are observed both in fetal alcohol syndrome (FAS) and in children with mutations in the gene for the cell adhesion molecule L1. We studied the effects of ethanol on cell-cell adhesion in mouse fibroblasts transfected with human L1. L1-transfected fibroblasts exhibited increased cell-cell adhesion compared with wild-type or vector-transfected controls. Ethanol potently and completely inhibited L1-mediated adhesion both in transfected L cells and NIH/3T3 cells. Half-maximal inhibition was observed at 7 mM ethanol, a concentration achieved in blood and brain after ingesting one alcoholic beverage. In contrast, ethanol did not inhibit the adhesion of fibroblasts transfected with vector alone or with N-CAM-140. L1-mediated cell-cell adhesion was inhibited with increasing potency by n-propanol and n-butanol, but was not inhibited at all by n-alcohols of 5 to 8 carbons, acetaldehyde, or acetate, suggesting that ethanol interacts directly with a small hydrophobic pocket within L1. Phenylalanine, teratogenic anticonvulsants, and high concentrations of glucose did not inhibit L1-mediated cell-cell adhesion. Ethanol also inhibited potently the heterotypic adhesion of rat cerebellar granule cells to a monolayer of L1-transfected NIH/3T3 cells, but had no effect on their adhesion to N-CAM-140 or vector-transfected NIH/3T3 cells. Because L1 plays a role in both neural development and learning, ethanol inhibition of L1-mediated cell-cell interactions could contribute to FAS and ethanol-associated memory disorders. PMID:8609170

  4. Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules

    Kazuhiko Nakamura; Kuniomi Honda; Takahiro Mizutani; Hirotada Akiho; Naohiko Harada

    2006-01-01

    The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which non-specifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Such recent advances in the understanding of the pathogenesis of IBD created a recent trend of novel biological therapies which specifically inhibit the molecules involved in the inflammatory cascade. Major targets for such treatment are inflammatory cytokines and their receptors, and adhesion molecules. A chimeric anti-TNF-α monoclonal antibody, infliximab, has become a standard therapy for CD and it is also likely to be beneficial for UC. Several anti-TNF reagents have been developed but most of them seem to not be as efficacious as infliximab. A humanized anti-TNF monoclonal antibody, adalimumab may be useful for the treatment of patients who lost responsiveness or developed intolerance to infliximab.Antibodies against IL-12 p40 and IL-6 receptor could be alternative new anti-cytokine therapies for IBD. Antiinterferon-γ and anti-CD25 therapies were developed,but the benefit of these agents has not yet been established. The selective blocking of migration of leukocytes into intestine seems to be a nice approach.Antibodies against α4 integrin and α4β7 integrin showed benefit for IBD. Antisense oligonucleotide of intercellular adhesion molecule 1 (ICAM-1) may be efficacious for IBD. Clinical trials of such compounds have been either recently reported or are currently underway. In this article, we review the efficacy and safety of such novel biological therapies for IBD.

  5. Effect of 16 Hz 30 dB infrasound on the expression of PSA-NCAM in the rat hippocampus%次声作用对大鼠海马PSA-NCAM表达的影响

    唐晨; 李玲; 袁华; 陈景藻

    2009-01-01

    Objective To observe the expression of polysialic acid-neural cell adhesion molecule (PSA-NCAM) in the rat hippocampus after infrasound exposure. Methods Ninety-six Sprague-Dawley rats were random-ized into a 16 Hz 130 dB infrasound exposure group (n =72) and a control group (n =24). Rats of the infrasound exposure group were exposed to 16 Hz 130 dB infrasound in a barochamber 2 h/d for 1, 7, 14 and 21 d. The rats' brains were removed and immunohistochemieal methods were used to detect the expression of PSA-NCAM in the hip-pocampus on the 1st, 7th, 14th, and 21st day during treatment and on the lat, 7th, and 14th day after the treatment ended. Results The expression of PSA-NCAM in the rats' hippocampuses increased after exposure for 1 d, reached its peak at the 14th day, then had decreased by the 21st day but remained at a higher level than in the controls (P≤ 0.05). Conclusion The expression of PSA-NCAM in the rat hippocampus is increased by exposure to 16 Hz 130 dB infrasound, but the levels recover somewhat after infrasound exposure ends. lnfrasound could induce neural injury and promote the migration of neural stem cells. PSA-NCAM might participate in the repair of neural injuries re-suiting from infrasound exposure.%目的 研究实验大鼠海马区多聚唾液酸神经细胞黏附因子(PSA.NCAM)经次声作用后的表达情况.方法 将96只SD大鼠随机分为次声作用组和对照组,将次声作用组大鼠暴露于16 Hz,130 dB次声环境中,2 h/d;对照组大鼠于相同时间置于次声压力舱内,但期间不给予次声干预.采用免疫组织化学染色法观察次声作用后不同时间点(次声作用后第1、7、14及21天)及次声结束后即日、第7天和第14天时大鼠海马区PSA-NCAM的表达情况.结果 大鼠海马区PSA-NCAM于次声作用1 d后即开始增加,于次声连续作用第14天时达到峰值,第21天后有所降低,但仍显著高于对照组水平(P<0.05).当停止次声作用后,发现实验大鼠海马

  6. Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow

    Yang H

    2011-09-01

    Full Text Available Hong Yang, Xiaoyan Xiong, Lie Zhang, Chunhui Wu, Yiyao LiuDepartment of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of ChinaAbstract: The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, microbubbles with a specific ligand to receptors expressed at the site of specific diseases are constructed. The present study aimed to engineer a novel type of bio-functionalized microbubbles (vascular cell adhesion molecule 1 [VCAM-1]-targeted microbubbles, and determine whether VCAM-1-targeted microbubbles exhibit specific adhesion to lipopolysaccharide (LPS-activated endothelial cells. Our data showed that VCAM-1expression was significantly upregulated in both LPS-activated endothelial cells in vitro and endothelium in a rat atherosclerosis model in vivo. Targeted microbubbles were designed by conjugating anti-VCAM-1 monoclonal antibodies to the shell of microbubbles using biotin–avidin bridging chemistry methods. Microbubble adhesion to endothelial cells was assessed in a flow chamber at two shear stress conditions (6.3 and 10.4 dynes/cm2. Our data showed that microbubble adhesion depends on both the surface anti-VCAM-1 antibody densities and the exposed shear stresses. Adhesion of VCAM-1-targeted microbubbles onto LPS-activated endothelial cells increased with the surface antibody densities, and decreased with the exposed shear stresses. These findings showed that the specific ligand-carrying microbubbles have considerable potential in targeted ultrasound molecular imaging or ultrasound-assisted drug/gene delivery applications.Keywords: targeted microbubbles, VCAM-1, adhesion, HUVEC-CS, shear flow

  7. 腰神经根损伤后神经细胞粘附分子(N-CAM)在神经肌肉接头部的表达%Expression of neural cell adhesion molecule at neuromuscular junction after lumber nerve root injury

    周重建; 侯宝兴; 王拥军; 刘梅; 施杞

    2003-01-01

    AIM: To investigate the expression of neural cell adhesion molecule(N-CAM) at the neuromuscular junction after lumber nerve root injury.METHODS: The distribution changes of N-CAM at flatfish muscle neuro-muscular junction of rat in its embryon phase, 14-day after birth, adulthood and 10, 20 and 30 days after its L5 lumber nerve root injury were observed by immunohistochemistry and confocal laser scanning microscopy technologies.RESULTS: N-CAM at muscle canal surface and neuromuscular junction were dyed intensively in strength at the embryon phase in rat, and the strength decreased during its growth and almost disappeared in its adulthood. However,N-CAM's repetition appeared after the innervation loss in muscle.Expression of N-CAM is regulated by the condition of nerve control.%目的:研究大鼠腰神经根损伤后,神经细胞黏附分子(N-CAM)在神经肌肉接头部的表达.方法:采用免疫组织化学方法和激光共聚焦显微扫描(confocal iaserscaring microscopy)技术,观察了大鼠胚胎期,出生后14 d,成年期以及L5神经根受压后10,20,和30 d,大鼠比且鱼肌神经肌肉接头部N-CAM的分布变化.结果:大鼠胚胎期,肌管的表面和神经肌肉接头部N-CAM呈强烈着染,在发育过程中其浓度逐渐减退,至成年肌肉时几乎消失.而当肌肉失神经支配后可导致N-CAM重新再现.结论:N-CAM在肌肉中的表达是通过神经支配状况调节的.

  8. Integrin Activation by Regulated Dimerization and Oligomerization of Platelet Endothelial Cell Adhesion Molecule (Pecam)-1 from within the Cell

    Zhao, Tieming; Newman, Peter J.

    2001-01-01

    Platelet endothelial cell adhesion molecule (PECAM)-1 is a 130-kD transmembrane glycoprotein having six Ig homology domains within its extracellular domain and an immunoreceptor tyrosine–based inhibitory motif within its cytoplasmic domain. Previous studies have shown that addition of bivalent anti–PECAM-1 mAbs to the surface of T cells, natural killer cells, neutrophils, or platelets result in increased cell adhesion to immobilized integrin ligands. However, the mechanism by which this occur...

  9. Comparative effect of genistein and daidzein on the expression of MCP-1, eNOS, and cell adhesion molecules in TNF-α-stimulated HUVECs

    Cho, Hye Yeon; Park, Chung Mu; Kim, Mi Jeong; Chinzorig, Radnaabazar; Cho, Chung Won; Song, Young Sun

    2011-01-01

    We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a do...

  10. Plasma matrix metalloproteinases, low density lipoprotein oxidisability and soluble adhesion molecules after a glucose load in Type 2 diabetes

    Brown Jackie

    2004-06-01

    Full Text Available Abstract Background Acute hyperglycaemia is an independent cardiovascular risk factor in Type 2 diabetes which may be mediated through increased oxidative damage to plasma low density lipoprotein, and in vitro, high glucose concentrations promote proatherogenic adhesion molecule expression and matrix metalloproteinase expression. Methods We examined these atherogenic risk markers in 21 subjects with Type 2 diabetes and 20 controls during an oral 75 g glucose tolerance test. Plasma soluble adhesion molecule concentrations [E-selectin, VCAM-1 and ICAM-1], plasma matrix metalloproteinases [MMP-3 and 9] and plasma LDL oxidisability were measured at 30 minute intervals. Results In the diabetes group, the concentrations of all plasma soluble adhesion molecules fell promptly [all p Conclusions A glucose load leads to a rapid fall in plasma soluble adhesion molecule concentrations in Type 2 diabetes and controls, perhaps reflecting reduced generation of soluble from membrane forms during enhanced leukocyte – endothelial adhesion or increased hepatic clearance, without changes in plasma matrix metalloproteinase concentrations or low density lipoprotein oxidisability. These in vivo findings are in contrast with in vitro data.

  11. Optical tweezers for single molecule force spectroscopy on bacterial adhesion organelles

    Andersson, Magnus; Axner, Ove; Uhlin, Bernt Eric; Fällman, Erik

    2006-08-01

    Instrumentation and methodologies for single molecule force spectroscopy on bacterial adhesion organelles by the use of force measuring optical tweezers have been developed. A thorough study of the biomechanical properties of fimbrial adhesion organelles expressed by uropathogenic E. coli, so-called pili, is presented. Steady-state as well as dynamic force measurements on P pili, expressed by E. coli causing pyelonephritis, have revealed, among other things, various unfolding and refolding properties of the helical structure of P pili, the PapA rod. Based on these properties an energy landscape model has been constructed by which specific biophysical properties of the PapA rod have been extracted, e.g. the number of subunits, the length of a single pilus, bond lengths and activation energies for bond opening and closure. Moreover, long time repetitive measurements have shown that the rod can be unfolded and refolded repetitive times without losing its intrinsic properties. These properties are believed to be of importance for the bacteria's ability to maintain close contact with host cells during initial infections. The results presented are considered to be of importance for the field of biopolymers in general and the development of new pharmaceuticals towards urinary tract infections in particular. The results show furthermore that the methodology can be used to gain knowledge of the intrinsic biomechanical function of adhesion organelles. The instrumentation is currently used for characterization of type 1 pili, expressed by E. coli causing cystitis, i.e. infections in the bladder. The first force spectrometry investigations of these pili will be presented.

  12. Human cell adhesion molecules: annotated functional subtypes and overrepresentation of addiction-associated genes.

    Zhong, Xiaoming; Drgonova, Jana; Li, Chuan-Yun; Uhl, George R

    2015-09-01

    Human cell adhesion molecules (CAMs) are essential for proper development, modulation, and maintenance of interactions between cells and cell-to-cell (and matrix-to-cell) communication about these interactions. Despite the differential functional significance of these roles, there have been surprisingly few systematic studies to enumerate the universe of CAMs and identify specific CAMs in distinct functions. In this paper, we update and review the set of human genes likely to encode CAMs with searches of databases, literature reviews, and annotations. We describe likely CAMs and functional subclasses, including CAMs that have a primary function in information exchange (iCAMs), CAMs involved in focal adhesions, CAM gene products that are preferentially involved with stereotyped and morphologically identifiable connections between cells (e.g., adherens junctions, gap junctions), and smaller numbers of CAM genes in other classes. We discuss a novel proposed mechanism involving selective anchoring of the constituents of iCAM-containing lipid rafts in zones of close neuronal apposition to membranes expressing iCAM binding partners. We also discuss data from genetic and genomic studies of addiction in humans and mouse models to highlight the ways in which CAM variation may contribute to a specific brain-based disorder such as addiction. Specific examples include changes in CAM mRNA splicing mediated by differences in the addiction-associated splicing regulator RBFOX1/A2BP1 and CAM expression in dopamine neurons. PMID:25988664

  13. Junctional adhesion molecule-C (JAM-C) regulates polarized neutrophil transendothelial cell migration in vivo

    Woodfin, Abigail; Voisin, Mathieu-Benoit; Beyrau, Martina; Colom, Bartomeu; Caille, Dorothée; Diapouli, Frantzeska-Maria; Nash, Gerard B; Chavakis, Triantafyllos; Albelda, Steven M.; Rainger, G Ed; Meda, Paolo; Imhof, Beat A.; Nourshargh, Sussan

    2011-01-01

    Neutrophil migration into inflamed tissues is a fundamental component of innate immunity. A decisive step in this process is the polarised migration of blood neutrophils through endothelial cells (ECs) lining the venular lumen (transendothelial cell migration; TEM) in a luminal to abluminal direction. Using real-time confocal imaging we report that neutrophils can exhibit disrupted polarised TEM (“hesitant” and “reverse”) in vivo. These events were noted in inflammation following ischemia-reperfusion injury, characterised by reduced expression of junctional adhesion molecule C (JAM-C) from EC junctions, and were enhanced by EC JAM-C blockade or genetic deletion. The results identify JAM-C as a key regulator of polarised neutrophil TEM in vivo and suggest that reverse TEM neutrophils can contribute to dissemination of systemic inflammation. PMID:21706006

  14. Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion

    1992-01-01

    Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid indu...

  15. Adhesion molecules in subjects with COPD and healthy non-smokers: a cross sectional parallel group study

    Blidberg, Kristin; Palmberg, Lena; James, Anna; Billing, Bo; Henriksson, Elisabeth; Lantz, Ann-Sofie; Larsson, Kjell; Dahlén, Barbro

    2013-01-01

    Background The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD. Methods Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included. Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, C...

  16. Effect of irradiation on gene expression of rat liver adhesion molecules. In vivo and in vitro studies

    Moriconi, Federico; Malik, Ihtzaz; Ahmad, Ghayyor; Dudas, Joszef; Ramadori, Giuliano [Dept. of Gastroenterology and Endocrinology, Goettingen Univ. (Germany); Rave-Fraenk, Margret; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans [Dept. of Radiotherapy, Goettingen Univ. (Germany)

    2009-07-15

    Background and purpose: Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro. Material and methods: Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology. Results: Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), {beta}{sub 1}-integrin, {beta}{sub 2}-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, {beta}{sub 1}-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), {beta}{sub 2}-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-){alpha}, interleukin-(IL-)1{beta}, or IL-6 plus TNF-{alpha} led to an upregulation of P-selectin, ICAM-1 and VCAM-1. Conclusion: The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of

  17. Soluble adhesion molecules ICAM-1, VCAM-1, P-selectin in children with Helicobacter pylori infection

    Elzbieta Maciorkowska; Maciej Kaczmarski; Anatol Panasiuk; Katarzyna Kondej-Muszynska; Andrzej Kemonai

    2005-01-01

    AIM: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children withHelicobacter pylori(H pylori)infection and to evaluate their significance for the morphological changes found in gastric mucosa.METHODS: The study included 106 children: 59children (55.7%) with chronic gastritis and positive IgG against H pylori, 29 children (27.3%) after previous H pylori infection without the bacterium colonization but with positive IgG against H pylori, and 18 children (17%) with functional disorders of the gastrointestinal system but with normal IgG against H pylori. Endoscopic and histopathological evaluation of gastric mucosa was performed based on the Sydney System classification.The evaluation of sP-selectin, sIC AM-1, sVCAM-1 levels in the sera of children was carried out using ELISA test.RESULTS: The assessment of gastritis activity degrees indicated statistically significant values in the antrum and corpus (P<0.001) of children examined. Serum sVCAM-1 levels were higher in group with gastritis due to H pylori infection than in group without infection and differed statistically (P<0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive molecules in infected children and decreased after eradication of H pylori. Serum sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were similar in children with and without H pylori infection.CONCLUSION: Assessment of adhesive molecules (sPselectin, sICAM-1, sVCAM-1) in the sera of children with active H pylori infection can show the participation of sVCAM-1 in the pathogenesis of gastric mucosal inflammation, sP-selectin and sICAM-1 concentrations in the sera of children with H pylori infection after eradication cannot reveal any significant differences as compared to healthy children.

  18. The Neuroplastin adhesion molecules: key regulators of neuronal plasticity and synaptic function.

    Beesley, Philip W; Herrera-Molina, Rodrigo; Smalla, Karl-Heinz; Seidenbecher, Constanze

    2014-11-01

    The Neuroplastins Np65 and Np55 are neuronal and synapse-enriched immunoglobulin superfamily molecules that play important roles in a number of key neuronal and synaptic functions including, for Np65, cell adhesion. In this review we focus on the physiological roles of the Neuroplastins in promoting neurite outgrowth, regulating the structure and function of both inhibitory and excitatory synapses in brain, and in neuronal and synaptic plasticity. We discuss the underlying molecular and cellular mechanisms by which the Neuroplastins exert their physiological effects and how these are dependent upon the structural features of Np65 and Np55, which enable them to bind to a diverse range of protein partners. In turn this enables the Neuroplastins to interact with a number of key neuronal signalling cascades. These include: binding to and activation of the fibroblast growth factor receptor; Np65 trans-homophilic binding leading to activation of p38 MAPK and internalization of glutamate (GluR1) receptor subunits; acting as accessory proteins for monocarboxylate transporters, thus affecting neuronal energy supply, and binding to GABAA α1, 2 and 5 subunits, thus regulating the composition and localization of GABAA receptors. An emerging theme is the role of the Neuroplastins in regulating the trafficking and subcellular localization of specific binding partners. We also discuss the involvement of Neuroplastins in a number of pathophysiological conditions, including ischaemia, schizophrenia and breast cancer and the role of a single nucleotide polymorphism in the human Neuroplastin (NPTN) gene locus in impairment of cortical development and cognitive functions. Neuroplastins are neuronal cell adhesion molecules, which induce neurite outgrowth and play important roles in synaptic maturation and plasticity. This review summarizes the functional implications of Neuroplastins for correct synaptic membrane protein localization, neuronal energy supply, expression of LTP and LTD

  19. Adenovirus viral interleukin-10 inhibits adhesion molecule expressions induced by hypoxia/reoxygenation in cerebrovascular endothelial cells1

    Hui KANG; Peng-yuan YANG; Yao-cheng RUI

    2008-01-01

    Aim: To investigate the effects of recombinant adenovirus encoding viral interleukin-10 (vIL-10), a potent anti-inflammatory cytokine, on adhesion mol-ecule expressions and the adhesion rates of leukocytes to endothelial cells in cerebrovascular endothelial cells injured by hypoxia/reoxygenation (H/R). Methods: A recombinant adenovirus expressing vIL-10 (Ad/vIL-10 (or the green fluorescent protein (Ad/GFP) gene was constructed. A cerebrovascular endothe-lial cell line bend.3 was pretreated with a different multiplicity of infection (MOI) of Ad/vIL-10 or Ad/GFP and then exposed to hypoxia for 9 h followed by reoxygenation for 12 h. The culture supernatants were tested for the expression of vIL-10 and endogenous murine IL-10 (mIL-10) by ELISA. The effects of Ad/vIL-10 on monocyte-endothelial cell adhesion were represented as the adhesion rate. Subsequently, the expressions of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1(VCAM-1) in the endothelial cells after treat-ment with Ad/vIL-10 and H/R were analyzed by Western blotting and real-time PCR. Results: vIL-10 was expressed in cultured bEnd.3 after Ad/vIL-10 transfec-tion and was significantly increased by H/R. Ad/vIL-10 or Ad/GFP did not affect the mlL-10 level. H/R increased the mIL-10 expression, but insignificantly. Mono-cyte-endothelial cell adhesion induced by H/R was significantly inhibited by pretreatment with Ad/vIL-10 (MOI: 80). ICAM-I, and VCAM-1 in bEnd.3 and were significantly increased after H/R, while pretreatment with Ad/vIL-10 (MOI: 80) significantly inhibited their expressions. Ad/GFP did not markedly affect mono-cyte-endothelial adhesion and the expressions of ICAM-1 and VCAM-1 induced by H/R. Conclusion: Ad/vIL-10 significantly inhibits the upregulation of endot-helial adhesion molecule expressions and the increase of adhesion of monocytes-endothelial cells induced by H/R, indicating that vIL-10 gene transfer is of far-reaching significance in the therapy of

  20. Cellular adhesion molecules on endothelial cells participate in radiation-mediated inflammation

    Purpose: The acute and subacute clinical manifestations of ionizing radiation mimic the inflammatory response to a number of stimuli. During the early stages of the inflammatory response, endothelial cells rapidly and transiently express a number of glycoproteins such as E-selectin, P-selectin, ICAM-1 and VCAM-1 which influence leucocyte adhesion. We quantified the expression of these cellular adhesion molecules (CAMs) in irradiated endothelial cells in order to determine whether these glycoproteins participate in radiation-mediated inflammation. Methods: Primary cultures of human umbilical vein endothelial cells (HUVEC) and HMEC cells were grown to 90% confluence and irradiated with a GE Maxitron x-ray generator. The cells were incubated with primary IgG1 antibody (mouse anti-human ICAM-1, VCAM-1, P-selectin and E-selectin and incubated with FITC-conjugated secondary antibody (goat anti-mouse IgG1). Fluorescence-activated cell sorting (FACS) analysis was utilized for quantitation of receptor expression of each CAM on irradiated endothelial cells. Electrophoretic mobility gel shift assays of nuclear protein extracts from irradiated HUVEC cells were performed using the E-selectin NFkB binding sequence (5'AGCTTAGAGGGGATTTCCGAGAGGA-3'). The E-selectin promoter was ligated to the growth hormone reporter. Plasmids pE-sel(-587 +35)GH or pE-sel(-587 +35)GH Δ NFκB (5 μg) was transfected into HMEC or HUVEC cells by use of lipofection. Transfectants were incubated for 16 h after transfection followed by treatment with 10 Gy (1 Gy/min, GE Maxitron) of ionizing radiation, and or with TNF or IL-1. Leukocyte adhesion to irradiated endothelial cells was quantified by HL-60 binding. Results: The log fluorescence of cells incubated with the antibody to E-selectin shifted by 32% at 4 h after irradiation. In comparison, a shift of 35% occurred 20 h after irradiation for cells incubated with the antibody to ICAM. However, there was no significant increase in P-selectin or VCAM

  1. Cryptotanshinone inhibits oxidized LDL-induced adhesion molecule expression via ROS dependent NF-κB pathways.

    Zhao, Wenwen; Wu, Chuanhong; Chen, Xiuping

    2016-05-01

    Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, play important roles in the initial stage of atherosclerosis. Cryptotanshinone (CPT), a natural compound isolated from Salvia miltiorrhiza Bunge, exhibits anti-atherosclerotic activity although the underlying mechanisms remain elusive. In this study, the protective effect of CPT against oxidized low-density lipoprotein (ox-LDL)-induced adhesion molecule expression was investigated in human umbilical vein endothelial cells. Ox-LDL significantly induced ICAM-1, VCAM-1, and E-selectin expression at the mRNA and protein levels but reduced eNOS phosphorylation and NO generation, which were reversed by CPT pretreatment. Sodium nitroprusside, a NO donor, N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger, and BAY117082, a NF-κB inhibitor, inhibited ox-LDL-induced ICAM-1, VCAM-1, and E-selectin expression. Ox-LDL-induced ROS production was significantly inhibited by CPT and NAC. Furthermore, ox-LDL activated the NF-κB signaling pathway by inducing phosphorylation of IKKβ and IκBα, promoting the interaction of IKKβ and IκBα, and increasing p65 nuclear translocation, which were significantly inhibited by CPT. In addition, CPT, NAC, and BAY117082 inhibited ox-LDL-induced membrane expression of ICAM-1, VCAM-1, E-selectin, and endothelial-monocyte adhesion and restored eNOS phosphorylation and NO generation. Results suggested that CPT inhibited ox-LDL-induced adhesion molecule expression by decreasing ROS and inhibiting the NF-κB pathways, which provides new insight into the anti-atherosclerotic mechanism of CPT. PMID:26647279

  2. Osteoblast adhesion to orthopaedic implant alloys: effects of cell adhesion molecules and diamond-like carbon coating.

    Kornu, R; Maloney, W J; Kelly, M A; Smith, R L

    1996-11-01

    In total joint arthroplasty, long-term outcomes depend in part on the biocompatibility of implant alloys. This study analyzed effects of surface finish and diamond-like carbon coating on osteoblast cell adhesion to polished titanium-aluminum-vanadium and polished or grit-blasted cobalt-chromium-molybdenum alloys. Osteoblast binding was tested in the presence and absence of the cell adhesion proteins fibronectin, laminin, fibrinogen, and vitronectin and was quantified by measurement of DNA content. Although adherence occurred in serum-free medium, maximal osteoblast binding required serum and was similar for titanium and cobalt alloys at 2 and 12 hours. With the grit-blasted cobalt alloy, cell binding was reduced 48% (p Coating the alloys with diamond-like carbon did not alter osteoblast adhesion, whereas fibronectin pretreatment increased cell binding 2.6-fold (p enhance cell adhesion. These results support the hypothesis that cell adhesion proteins can modify cell binding to orthopaedic alloys. Although osteoblast binding was not affected by the presence of diamond-like carbon, this coating substance may influence other longer term processes, such as bone formation, and deserves further study. PMID:8982128

  3. Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow

    Liu, Yiyao

    2011-01-01

    Hong Yang, Xiaoyan Xiong, Lie Zhang, Chunhui Wu, Yiyao LiuDepartment of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of ChinaAbstract: The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, mic...

  4. Influence of levofloxacin on soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of patients with pulmonary tuberculosis

    Qing-Zhou He; Qian-Shu Hu

    2016-01-01

    Objective:To observe the influence of levofloxacin on soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of patients with pulmonary tuberculosis. Methods:A total of 50 patients with pulmonary tuberculosis who had been treated in our hospital from March 2014 to April 2015 were randomly divided into the control group (conventional treatment) and the observation group (conventional treatment plus levofloxacin). Each group had 25 cases. Then, the soluble selection,interleukin,adhesion molecule and pulmonary surfactant protein levels of the two groups at the second, fourth and sixth months before and after treatment were compared. Results:Before treatment, the differencess of the levels of the soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of the two groups were significant (P>0.05), while the detection levels of all the aspects of the observation group at the second, fourth and sixth months after treatment were all significantly lower than those of the control group (P<0.05). The detection results of the two groups at the second, fourth and sixth months after treatment showed significant differences. Conclusions:Lvofloxacin has significant effect on the soluble selection, interleukin, adhesion molecule and pulmonary surfactant protein of patients with pulmonary tuberculosis.

  5. Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study

    A.E. Hak (Liesbeth); H.A.P. Pols (Huib); C.D. Stehouwer (Coen); J. Meijer (John); A.J. Kiliaan (Amanda); M.M.B. Breteler (Monique); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2001-01-01

    textabstractInsulin resistance, which is highly prevalent in the elderly, is suggested to be accompanied by an increased acute phase response. Until now, it is unclear whether cellular adhesion molecules are involved in the clustering of insulin resistance. In the present study, we

  6. Functional mapping of the cytoplasmic region of intercellular adhesion molecule-3 reveals important roles for serine residues

    Hayflick, J S; Stine, J; Fox, R; Hoekstra, D; Gallatin, W M

    1997-01-01

    Intercellular adhesion molecule-3 (ICAM-3), a ligand for beta2 integrins, elicits a variety of activation responses in lymphocytes. We describe a functional mapping study that focuses on the 37-residue cytoplasmic region of ICAM-3. Carboxyl-terminal truncations delineated portions involved in T cell

  7. Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1

    Brown, Alan; Turner, Louise; Christoffersen, Stig;

    2013-01-01

    The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria. The...

  8. Platelet endothelial cell adhesion molecule-1 polymorphism in patients with bronchial asthma.

    Ebrahim Nadi

    2012-12-01

    Full Text Available Asthma is considered as a chronic inflammatory airway disease and defined as increased tracheobronchial responsiveness to variety of stimuli. Edema and inflammatory cell infiltration in airway is observed in the asthmatic patients. One of the essential changes in inflammation is adhesion of leukocyte to endothelium and transmigration of leukocytes to the sites of inflammation. Unfortunately, little is known about the role of platelet endothelial cell adhesion molecule-1 (PECAM-1 polymorphism in asthma inflammatory process. The purpose of this study was to determine whether PECAM-1 polymorphisms affect the risk of asthma or not.Forty-five asthmatic patients (including 27 men and 18 women and 45 healthy volunteers (11 men and 34 women were studied. To determine the severity of the asthmas situation, a questionnaire was prepared asking the following information: age, sex, clinical signs and symptoms and past medical history. All subjects were genotyped for PECAM-1 polymorphism by using amplification refractory mutation system -polymerase chain reaction (ARMS-PCR. The genotype distribution of PECAM-1 80 Val/Met polymorphism in all asthmatic patients were Val/Val while non asthmatic controls were 95.6% Val/Val and 4.4% Val/Met. However, these differences were not statistically significant (p<0.05. The allele and genotype frequencies of PECAM-1 125 Val/Leu polymorphism were significantly different between asthmatic patients and controls. On the other hand, the presence of 125 Leu allele was associated with an increasing risk of asthma with an odds ratio of 2.8 (95% CI; 1.5-5.3, p=0.002. Our findings suggest that the PECAM-1 125 Val/leu polymorphism might be a genetic factor that may be associated with asthma.

  9. Expression of intercellular adhesion molecule-1and HLA-DR antigens in uveitis

    1999-01-01

    目的:研究细胞间粘附分子-1(intellular adhesion molecule-1,ICAM-1)和人体组织相关抗原(human leudocyte antigen,HLA-DR)在萄萄膜炎免疫反应中的作用.方法:应用免疫组织化学染色检查20只正常眼和54例葡萄糖膜炎眼球摘除眼(其中外源性33例和内源性21例)的脉络膜和视网膜组织中ICAM-1和HLA-DR的表达.结果:正常眼的脉络膜和视网膜组织没有ICAM-1的阳性染色,没有或较少有HLA-DR的表达,葡萄膜炎眼中二者有增高表达(P<0.01),而外源性和内源性葡萄膜炎眼组间表达统计学上无显著差异(P>0.05).结论:ICAM-1、HLA-DR分子能够介导白细胞和炎症部位组织细胞的识别和粘附,二者的共同表达说明它们在葡萄糖膜炎脉络膜视网膜组织的免疫性损伤中具有重要意义.%Objective :To study the effects of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen (HAL-DR) on the immunopathologic process of uveitis. Methods:Imn- munohistochemical techniques were applied to detect their expression in eyes of both the health (20 cases from eye bank) and patients with uveitis (54 cases with 54 eyes which included 33 ex- ogenous uveitis and 21 endogenous one). Results:Both the two ant igens were detectable in the choroidal and retinal tissues in eyes of uveitis while all the normal eyes showed negative expres- sion of ICAM-1 and negative or little expression of HLA-DR (P<0. 01). However,there was no statistically significant difference between exogenous and endogenous types (P>0. 05). Conclu- sion: Both ICAM-1 and HLA-DR may be responsible for cell recognition and binding in the in- flarnmatory tissues. The co-expression of ICAM-1 and HAL-DR showed that these two factors might play an important role in the immunologic damage of the choroid and retina in uveitis.

  10. Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

    Tyagi Prajesh K

    2008-12-01

    Full Text Available Abstract Background Host adhesion molecules play a significant role in the pathogenesis of Plasmodium falciparum malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, ICAM1, PECAM1 and CD36, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India. Methods The frequency distribution of seven selected SNPs of ICAM1, PECAM1 and CD36 was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR for risk assessment was estimated using EpiInfo™ version 3.4. Results Association of the ICAM1 rs5498 (exon 6 G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively. The CD36 rs1334512 (-53 T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004. Interestingly, a SNP of the PECAM1 gene (rs668, exon 3, C/G with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region. Conclusion The data highlights the significance of variations in the ICAM1, PECAM1 and CD36 genes in the manifestation of falciparum malaria in India. The PECAM1 exon 3 SNP exhibits altered association with disease in the

  11. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin Volmer;

    2003-01-01

    phosphatidylinositol 3-kinase (PI3K) is required for NCAM-mediated neurite outgrowth from PC12-E2 cells and from cerebellar and dopaminergic neurones in primary culture, and that the thr/ser kinase Akt/protein kinase B (PKB) is phosphorylated downstream of PI3K after stimulation with C3. Moreover, we present data...

  12. Intercellular adhesion molecule 1 promotes HIV-1 attachment but not fusion to target cells.

    Naoyuki Kondo

    Full Text Available Incorporation of intercellular adhesion molecule 1 (ICAM-1 into HIV-1 particles is known to markedly enhance the virus binding and infection of cells expressing lymphocyte function-associated antigen-1 (LFA-1. At the same time, ICAM-1 has been reported to exert a less pronounced effect on HIV-1 fusion with lymphoid cells. Here we examined the role of ICAM-1/LFA-1 interactions in productive HIV-1 entry into lymphoid cells using a direct virus-cell fusion assay. ICAM-1 promoted HIV-1 attachment to cells in a temperature-dependent manner. It exerted a marginal effect on virus binding in the cold, but enhanced binding up to 4-fold at physiological temperature. ICAM-1-independent attachment in the cold was readily reversible upon subsequent incubation at elevated temperature, whereas ICAM-1-bearing particles were largely retained by cells. The better virus retention resulted in a proportional increase in HIV-1 internalization and fusion, suggesting that ICAM-1 did not specifically accelerate endocytosis or fusion steps. We also measured the rates of CD4 engagement, productive endocytosis and HIV-endosome fusion using specific fusion inhibitors. These rates were virtually independent of the presence of ICAM-1 in viral particles. Importantly, irrespective of the presence of ICAM-1, HIV-1 escaped from the low temperature block, which stopped virus endocytosis and fusion, much later than from a membrane-impermeant fusion inhibitor targeting surface-accessible particles. This result, along with the complete inhibition of HIV-1 fusion by a small molecule dynamin inhibitor, implies this virus enters lymphoid cells used in this study via endocytosis and that this pathway is not altered by the viral ICAM-1. Our data highlight the role of ICAM-1 in stabilizing the HIV-1 attachment to LFA-1 expressing cells, which leads to a proportional enhancement of the receptor-mediated uptake and fusion with endosomes.

  13. Netrin-1 induces local translation of down syndrome cell adhesion molecule in axonal growth cones.

    Jain, Shruti; Welshhans, Kristy

    2016-07-01

    Down syndrome cell adhesion molecule (DSCAM) plays an important role in many neurodevelopmental processes such as axon guidance, dendrite arborization, and synapse formation. DSCAM is located in the Down syndrome trisomic region of human chromosome 21 and may contribute to the Down syndrome brain phenotype, which includes a reduction in the formation of long-distance connectivity. The local translation of a select group of mRNA transcripts within growth cones is necessary for the formation of appropriate neuronal connectivity. Interestingly, we have found that Dscam mRNA is localized to growth cones of mouse hippocampal neurons, and is dynamically regulated in response to the axon guidance molecule, netrin-1. Furthermore, netrin-1 stimulation results in an increase in locally translated DSCAM protein in growth cones. Deleted in colorectal cancer (DCC), a netrin-1 receptor, is required for the netrin-1-induced increase in Dscam mRNA local translation. We also find that two RNA-binding proteins-fragile X mental retardation protein (FMRP) and cytoplasmic polyadenylation element binding protein (CPEB)-colocalize with Dscam mRNA in growth cones, suggesting their regulation of Dscam mRNA localization and translation. Finally, overexpression of DSCAM in mouse cortical neurons results in a severe stunting of axon outgrowth and branching, suggesting that an increase in DSCAM protein results in a structural change having functional consequences. Taken together, these results suggest that netrin-1-induced local translation of Dscam mRNA during embryonic development may be an important mechanism to regulate axon growth and guidance in the developing nervous system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 799-816, 2016. PMID:26518186

  14. High expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 and 8 in primary myelofibrosis

    Hasselbalch, Hans Carl; Skov, Vibe; Larsen, Thomas Stauffer; Thomassen, Mads; Riley, Caroline Hasselbalch; Jensen, Morten; Bjerrum, Ole Weis; Kruse, Torben A

    2011-01-01

    Primary myelofibrosis (PMF) is characterized by leukoerythroblastic anemia with circulating immature myeloid cells, including CD34+ cells, progressive splenomegaly and accumulation of connective tissue and neoangiogenesis in the bone marrow. Altered bone marrow stroma and cell adherence account for...... the egress of CD34+ cells from the bone marrow. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6 has been implicated in cell adhesion, cellular invasiveness, angiogenesis, and inflammation, which are all key processes in the pathophysiology of PMF. Accordingly, CEACAMs may play an...

  15. Evaluation of Activated Leukocyte Cell Adhesion Molecule as a Biomarker for Breast Cancer in Egyptian Patients

    In this study, serum activated leukocyte cell adhesion molecule (ALCAM) levels were evaluated in 41 primary breast cancer patients and 20 healthy females, and its diagnostic value was quantified, and compared with those of carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA). Also, its prognostic value was examined. Serum ALCAM levels were also evaluated before and after surgical treatment. Serum levels of ALCAM and CA 15-3 were significantly higher in breast cancer patients than healthy controls (P=0.002, P=0.043 respectively), but the difference in serum CEA levels did not reach statistical significance. Serum ALCAM levels had significant area under the curve (AUC) (P=0.002), but serum levels of CA 15-3 and CEA had nonsignificant AUCs, and various combinations between them did not result in any improvement. A significant association was found between serum levels of ALCAM and CEA with age and menopausal status in breast cancer patients. Non-significant difference was shown in serum levels of ALCAM, CA 15-3 and CEA before and after surgical treatment. In conclusion, this study suggests that serum ALCAM may represent a novel diagnostic bio marker for breast cancer

  16. Adhesion molecules levels in blood correlate with MRI activity and clinical activity in multiple sclerosis

    Research into pathogenesis of multiple sclerosis (MS) has prompted efforts to identify immunological markers associated with disease activity. Adhesion molecules ICAM-1 and VCAM-1 are associated with inflammatory mediated blood-brain barrier (BBB) dysfunction. In this study investigates the correlation between blood level of circulating ICAM-1 and VCAM-1 and magnetic resonance imaging (MRI) activity in different clinical phases of patients with MS. We show that RRMS and SPMS patients in clinically active phase with Gd-enhancing lesions in CNS had higher blood levels of cICAM-1 and cVCAM-1 compared these parameters levers of RRMS patients in remission stage. These results suggest that cICAM-1 and cVCAM-1 is a sensitive indicator of disease activity associated with BBB inflammatory dysfunction. Elevated blood level of cICAM-1 more strongly correlated with clinical activity and BBB damage, than cVCAM-1 and that could be used as biological marker of disease activity. Circulating VCAM-1 as an early indicator of BBB disturbance, may also serve as marker of beneficial activity in relapses phase of MS course. (authors)

  17. Association of Intercellular Adhesion Molecule 1 (ICAM1 with Diabetes and Diabetic Nephropathy

    HarvestFGu

    2013-01-01

    Full Text Available Diabetes and diabetic nephropathy are complex diseases affected by genetic and environmental factors. Identification of the susceptibility genes and investigation of their roles may provide useful information for better understanding of the pathogenesis and for developing novel therapeutic approaches. Intercellular adhesion molecule 1 (ICAM1 is a cell surface glycoprotein expressed on endothelial cells and leukocytes in the immune system. The ICAM1 gene is located on chromosome 19p13 within the linkage region of diabetes. In the recent years, accumulating reports have implicated that genetic polymorphisms in the ICAM1 gene are associated with diabetes and diabetic nephropathy. Serum ICAM1 levels in diabetes patients and the icam1 gene expression in kidney tissues of diabetic animals are increased compared to the controls. Therefore, ICAM1 may play a role in the development of diabetes and diabetic nephropathy. In this review, we present genomic structure, variation and regulation of the ICAM1 gene, summarized genetic and biological studies of this gene in diabetes and diabetic nephropathy and discussed about the potential application using ICAM1 as a biomarker and target for prediction and treatment of diabetes and diabetic nephropathy.

  18. T cells, adhesion molecules and modulation of apoptosis in visceral leishmaniasis glomerulonephritis

    Goto Hiro

    2010-05-01

    Full Text Available Abstract Background Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L. chagasi that causes visceral leishmaniasis (VL. The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-α, IL-1α were searched and quantified. Results We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In

  19. Omentin inhibits TNF-α-induced expression of adhesion molecules in endothelial cells via ERK/NF-κB pathway

    Highlights: ► Omentin inhibited TNF-α-induced adhesion of THP-1 cells to HUVECs. ► Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-α in HUVECs. ► Omentin inhibits TNF-α-induced ERK and NF-κB activation in HUVECs. ► Omentin supreeses TNF-α-induced expression of ICAM-1 and VCAM-1 via ERK/NF-κB pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-α (TNF-α) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-α-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-α-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-α-activated signal pathway of nuclear factor-κB (NF-κB) by preventing NF-κB inhibitory protein (IκBα) degradation and NF-κB/DNA binding activity. Omentin pretreatment significantly inhibited TNF-α-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-α-induced NF-κB activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-α. These results suggest that omentin may inhibit TNF-α-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-κB pathway.

  20. Mice lacking the synaptic adhesion molecule Neph2/Kirrel3 display moderate hyperactivity and defective novel object preference

    Su Yeon eChoi

    2015-07-01

    Full Text Available Synaptic adhesion molecules regulate diverse aspects of neuronal synapse development, including synapse specificity, formation, and maturation. Neph2, also known as Kirrel3, is an immunoglobulin superfamily adhesion molecule implicated in intellectual disability, neurocognitive delay associated with Jacobsen syndrome, and autism spectrum disorders. We here report mice lacking Neph2 (Neph2–/– mice display moderate hyperactivity in a familiar but not novel environment and novel object recognition deficit with normal performances in Morris water maze spatial learning and memory, contextual fear conditioning and extinction, and pattern separation tests. These mice show normal levels of anxiety-like behaviors, social interaction, and repetitive behaviors. At the synapse level, Neph2–/– dentate gyrus granule cells exhibit unaltered dendritic spine density and spontaneous excitatory synaptic transmission. These results suggest that Neph2 is important for normal locomotor activity and object recognition memory.

  1. Nitric oxide pretreatment enhances atheroma component highlighting in vivo with intercellular adhesion molecule-1-targeted echogenic liposomes.

    Kee, Patrick H; Kim, Hyunggun; Huang, Shaoling; Laing, Susan T; Moody, Melanie R; Vela, Deborah; Klegerman, Melvin E; McPherson, David D

    2014-06-01

    We present an ultrasound technique for the detection of inflammatory changes in developing atheromas. We used contrast-enhanced ultrasound imaging with (i) microbubbles targeted to intercellular adhesion molecule-1 (ICAM-1), a molecule of adhesion involved in inflammatory processes in lesions of atheromas in New Zealand White rabbits, and (ii) pretreatment with nitric oxide-loaded microbubbles and ultrasound activation at the site of the endothelium to enhance the permeability of the arterial wall and the penetration of ICAM-1-targeted microbubbles. This procedure increases acoustic enhancement 1.2-fold. Pretreatment with nitric oxide-loaded echogenic liposomes and ultrasound activation can potentially facilitate the subsequent penetration of targeted echogenic liposomes into the arterial wall, thus allowing improved detection of inflammatory changes in developing atheromas. PMID:24613216

  2. Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules: the Normative Aging Study

    Vokonas Pantel S

    2011-05-01

    Full Text Available Abstract Background Particulate air pollution has been associated with cardiovascular morbidity and mortality, but it remains unclear which time windows and pollutant sources are most critical. MicroRNA (miRNA is thought to be involved in cardiovascular regulation. However, little is known about whether polymorphisms in genes that process microRNAs influence response to pollutant exposure. We hypothesized that averaging times longer than routinely measured one or two day moving averages are associated with higher soluble intercellular adhesion molecule-1 (sICAM-1 and vascular cell adhesion molecule-1 (sVCAM-1 levels, and that stationary and mobile sources contribute differently to these effects. We also investigated whether single nucleotide polymorphisms (SNPs in miRNA-processing genes modify these associations. Methods sICAM-1 and sVCAM-1 were measured from 1999-2008 and matched to air pollution monitoring for fine particulate matter (PM2.5 black carbon, and sulfates (SO42-. We selected 17 SNPs in five miRNA-processing genes. Mixed-effects models were used to assess effects of pollutants, SNPs, and interactions under recessive inheritance models using repeated measures. Results 723 participants with 1652 observations and 1-5 visits were included in our analyses for black carbon and PM2.5. Sulfate data was available for 672 participants with 1390 observations. An interquartile range change in seven day moving average of PM2.5 (4.27 μg/m3 was associated with 3.1% (95%CI: 1.6, 4.6 and 2.5% (95%CI: 0.6, 4.5 higher sICAM-1 and sVCAM-1. Interquartile range changes in sulfates (1.39 μg/m3 were associated with 1.4% higher (95%CI: 0.04, 2.7 and 1.6% (95%CI: -0.4, 3.7 higher sICAM-1 and sVCAM-1 respectively. No significant associations were observed for black carbon. In interaction models with PM2.5, both sICAM-1 and sVCAM-1 levels were lower in rs1062923 homozygous carriers. These interactions remained significant after multiple comparisons

  3. The role of cell adhesion molecules in visual circuit formation: From neurite outgrowth to maps and synaptic specificity

    Missaire, Mégane; Hindges, Robert

    2015-01-01

    ABSTRACT The formation of visual circuitry is a multistep process that involves cell–cell interactions based on a range of molecular mechanisms. The correct implementation of individual events, including axon outgrowth and guidance, the formation of the topographic map, or the synaptic targeting of specific cellular subtypes, are prerequisites for a fully functional visual system that is able to appropriately process the information captured by the eyes. Cell adhesion molecules (CAMs) with th...

  4. A Chinese Herbal Preparation Containing Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum Reduces Circulating Adhesion Molecules

    Kylie A. O’Brien

    2011-01-01

    Full Text Available Circulating adhesion molecules (CAMs, surface proteins expressed in the vascular endothelium, have emerged as risk factors for cardiovascular disease (CVD. CAMs are involved in intercellular communication that are believed to play a role in atherosclerosis. A Chinese medicine, the “Dantonic Pill” (DP (also known as the “Cardiotonic Pill”, containing three Chinese herbal material medica, Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum, has been used in China for the prevention and management of CVD. Previous laboratory and animal studies have suggested that this preparation reduces both atherogenesis and adhesion molecule expression. A parallel double blind randomized placebo-controlled study was conducted to assess the effects of the DP on three species of CAM (intercellular cell adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 and endothelial cell selectin (E-selectin in participants with mild-moderate hypercholesterolemia. Secondary endpoints included biochemical and hematological variables and clinical effects. Forty participants were randomized to either treatment or control for 12 weeks. Treatment with DP was associated with a statistically significant decrease in ICAM-1 (9% decrease, P = .03 and E-Selectin (15% decrease, P = .004. There was no significant change in renal function tests, liver function tests, glucose, lipids or C-reactive protein levels and clinical adverse effects did not differ between the active and the control groups. There were no relevant changes in participants receiving placebo. These results suggest that this herbal medicine may contribute to the development of a novel approach to cardiovascular risk reduction.

  5. The Drosophila cell adhesion molecule Klingon is required for long-term memory formation and is regulated by Notch

    Matsuno, Motomi; Horiuchi, Junjiro; Tully, Tim; Saitoe, Minoru

    2008-01-01

    The ruslan (rus) mutant was previously identified in a behavioral screen for mutants defective in long-lasting memory, which consists of two consolidated memory types, anesthesia-resistant memory, and protein synthesis-dependent long-term memory (LTM). We demonstrate here that rus is a new allele of klingon (klg), which encodes a homophilic cell adhesion molecule. Klg is acutely required for LTM but not anesthesia-resistant memory formation, and Klg expression increases upon LTM induction. LT...

  6. Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development

    Anderson, Garret R.; Galfin, Timothy; XU, WEI; Aoto, Jason; Malenka, Robert C.; Südhof, Thomas C.

    2012-01-01

    Mutations in the contactin-associated protein 2 (CNTNAP2) gene encoding CASPR2, a neurexin-related cell-adhesion molecule, predispose to autism, but the function of CASPR2 in neural circuit assembly remains largely unknown. In a knockdown survey of autism candidate genes, we found that CASPR2 is required for normal development of neural networks. RNAi-mediated knockdown of CASPR2 produced a cell-autonomous decrease in dendritic arborization and spine development in pyramidal neurons, leading ...

  7. Effect of spironolactone on renal and intercellular adhesion molecule-1 expression in Type 2 diabetic rats

    Objective: To observe the influence of spironolactone on the serum and urine intercellular adhesion molecule-1 (ICAM-1) level, and the change of renal structure and function of type 2 diabetic rats. Methods: 30 healthy male SD rats were chosen 10 of them were randomly selected as normal controls (group NC) n=10; Then these rats were randomly divided into type 2 diabetes group (group DM) n=10 and type 2 diabetes + spironolactone treated group (group SPI) n=10. After 8 weeks, the levels of blood glucose, serum lipids, urine biochemical, renal pathological changes were examined; while the serum and urine ICAM-1 levels changes were also detected. Results: 1. Compared with group NC, the levels of fBG and HbA1c were significantly increased in group DM and group SPI (P0.05). 2. After 8 weeks,the levels of ACR, URBP, UICAM-1, SICAM-1 and kidney/body weight ratio in group DM and group SPI were higher than group NC (P<0.05); the five indexes were significantly lower in group SPI compared with group DM (P<0.05). In addition, UICAM-1 excretion rate and SICAM-1 level showed positive correlations with ACR, URBP excretion rate and kidney/body weight ratio (P<0.01). 3. Pathology showed that the extent of glomerular lesions in rats in group SPI apparently reduced, ICAM-1 expression was decreased compared with that in group DM (P<0.01). Conclusion: Spironolactone can definitely protect type 2 diabetic kidney,and this protective effect was independent on the hypoglycemic effect. The mechanisms might be associated with its inhibition effect on ICAM-1 expression and its excretion. (authors)

  8. Intercellular Adhesion Molecule and Endogenous NOS Inhibitor: Asymmetric Dimethylarginine in Pregnant Women with Gestational Diabetes Mellitus

    Poniedziałek-Czajkowska, Elżbieta; Mierzyński, Radzisław; Szymula, Dariusz; Leszczyńska-Gorzelak, Bożena; Oleszczuk, Jan

    2016-01-01

    Objective. The aim of the study was to evaluate the concentrations of soluble intercellular adhesion molecule-1 (s-ICAM-1) and endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), as markers of endothelium dysfunction in patients with gestational diabetes mellitus (GDM). Patients and Methods. The levels of s-ICAM-1 and ADMA were analysed in the group of 56 patients with GDM and compared to 25 healthy pregnant women. The concentrations of s-ICAM-1 and ADMA were measured in serum using ELISA tests. Results. The groups did not differ by baseline descriptors: age (30.75 ± 6.32 versus 28.50 ± 4.95 years, NS) and gestational age (28.96 ± 2.85 versus 29.12 ± 2.96 hbd, NS). The patients with GDM were more obese (BMI 27.93 ± 7.02 versus 22.34 ± 4.21 kg/m2, p = 0.032) and had higher concentration of C-reactive protein (6.46 ± 6.03 versus 3.18 ± 3.83 mg/L, p = 0.029). In the GDM group the level of ADMA was lower (0.38 ± 0.17 versus 0.60 ± 0.28 μmol/L, p = 0.001) and the level of s-ICAM-1 was significantly higher (289.95 ± 118.12 versus 232.56 ± 43.31 ng/mL, p = 0.036) compared to controls. Conclusions. The pregnant women with GDM are characterized by higher concentration of s-ICAM-1 that reflects the activation and dysfunction of the endothelial cells. The decreased ADMA level in GDM patients seems to be preventive in the limitation of NO synthesis caused by the impaired insulin action and the endothelial dysfunction. PMID:26981539

  9. Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

    Kamran Ghaffarzadehgan; Mostafa Jafarzadeh; Hamid Reza Raziee; Harold Reza Sima; Ehsan Esmaili-Shandiz; Hanieh Hosseinnezhad; Ail Taghizadeh Kermani; Omeed Moaven; Maryam Bahrani

    2008-01-01

    AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was used for histological evaluation, including the type (Lauren's classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P=0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.

  10. Loss of cell adhesion molecule CHL1 improves homeostatic adaptation and survival in hypoxic stress.

    Huang, X; Sun, J; Rong, W; Zhao, T; Li, D H; Ding, X; Wu, L Y; Wu, K; Schachner, M; Xiao, Z C; Zhu, L L; Fan, M

    2013-01-01

    Close homologue of L1 (CHL1) is a transmembrane cell adhesion molecule that is critical for brain development and for the maintenance of neural circuits in adults. Recent studies revealed that CHL1 has diverse roles and is involved in the regulation of recovery after spinal cord injury. CHL1 expression was downregulated in the cerebral cortex, hypothalamus, and brain stem after the induction of acute hypoxia (AH). In the current study, we sought to address the role of CHL1 in regulating homeostasis responses to hypoxia using CHL1-knockout (CHL1(-/-)) mice. We found that, compared with wild-type littermates, CHL1(-/-) mice showed a dramatically lower mortality rate and an augmented ventilatory response after they were subjected to AH. Immunofluorescence staining revealed that CHL1 was expressed in the carotid body (CB), the key oxygen sensor in rodents, and CHL1 expression level in the CB as assayed by western blot was decreased after hypoxic exposure. The number of glomus cells and the expression of tyrosine hydroxylase (a marker for glomus cells) in the CB of CHL1(-/-) mice appeared to be increased compared with CHL1(+/+) mice. In addition, in the ex vivo CB preparation, hypoxia induced a significantly greater afferent nerve discharge in CHL1(-/-) mice compared with CHL1(+/+) mice. Furthermore, the arterial blood pressure and plasma catecholamine levels of CHL1(-/-) mice were also significantly higher than those of CHL1(+/+) mice. Our findings first demonstrate that CHL1 is a novel intrinsic factor that is involved in CB function and in the ventilatory response to AH. PMID:23949217