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Sample records for adhesion molecule stabilization

  1. Wheat proteins enhance stability and function of adhesion molecules in cryopreserved hepatocytes.

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    Grondin, Mélanie; Hamel, Francine; Averill-Bates, Diana A; Sarhan, Fathey

    2009-01-01

    Cryopreserved hepatocytes with good hepatospecific functions upon thawing are important for clinical transplantation and for in vitro drug toxicity testing. However, cryopreservation reduces viability and certain hepatospecific functions, but the most pronounced change is diminished attachment efficiency of hepatocytes. Adhesion of cells to the extracellular matrix and cell-cell contacts are crucial for many aspects of cellular function. These processes are partly mediated and controlled by cellular adhesion molecules. The mechanisms responsible for reduced attachment efficiency of cryopreserved hepatocytes are not well understood. To address this question, we investigated the effect of a new cryopreservation procedure, using wheat proteins (WPs) or mixtures of recombinant forms of wheat freezing tolerance-associated proteins, on the stability of three important adhesion molecules (beta1-integrin, E-cadherin, and beta-catenin). Immunoblot analyses revealed that the levels of beta1-integrin, E-cadherin, and beta-catenin were much lower in cryopreserved rat hepatocytes, when compared to fresh cells. Protein expression of the adhesion molecules was generally lower in cells cryopreserved with DMSO, compared to WPs. Moreover, the stability of the adhesion molecules was not affected by cryopreservation to the same degree, with more pronounced decreases occurring for beta1-integrin (62-74%) > beta-catenin (51-58%) > E-cadherin (21-37%). However, when hepatocytes were cryopreserved with partially purified WPs (SulWPE, AcWPE) or with mixtures of recombinant wheat proteins, there was a clear protective effect against the loss of protein expression of beta1-integrin, E-cadherin, and beta-catenin. Protein expression was only 10-20% lower than that observed in fresh hepatocytes. These findings clearly demonstrate that WPs, and more particularly, partially purified WPs and recombinant wheat proteins, were more efficient for cryopreservation of rat hepatocytes by maintaining good

  2. [Endothelial cell adhesion molecules].

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    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu

    2014-01-01

    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  3. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    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...

  4. Cell adhesion molecules and sleep.

    Science.gov (United States)

    O'Callaghan, Emma Kate; Ballester Roig, Maria Neus; Mongrain, Valérie

    2017-03-01

    Cell adhesion molecules (CAMs) play essential roles in the central nervous system, where some families are involved in synaptic development and function. These synaptic adhesion molecules (SAMs) are involved in the regulation of synaptic plasticity, and the formation of neuronal networks. Recent findings from studies examining the consequences of sleep loss suggest that these molecules are candidates to act in sleep regulation. This review highlights the experimental data that lead to the identification of SAMs as potential sleep regulators, and discusses results supporting that specific SAMs are involved in different aspects of sleep regulation. Further, some potential mechanisms by which SAMs may act to regulate sleep are outlined, and the proposition that these molecules may serve as molecular machinery in the two sleep regulatory processes, the circadian and homeostatic components, is presented. Together, the data argue that SAMs regulate the neuronal plasticity that underlies sleep and wakefulness. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  5. Adhesion molecules in experimental phacoanaphylactic endophthalmitis.

    Science.gov (United States)

    Till, G O; Lee, S; Mulligan, M S; Wolter, J R; Smith, C W; Ward, P A; Marak, G E

    1992-11-01

    Intraocular accumulation of inflammatory neutrophils is an important feature of experimental phacoanaphylactic endophthalmitis (EPE). Increasing evidence suggests that localization of neutrophils to the site of inflammation requires the participation of neutrophil and endothelial adhesion molecules. These studies were undertaken to determine if blocking of adhesion molecules on neutrophils (CD18) or endothelium (ELAM-1) could attenuate EPE in Lewis rats. Treatment of experimental animals with anti-CD18 or anti-ELAM-1 significantly suppressed intraocular neutrophil accumulation, retinal hemorrhage, and vasculitis, and attenuated retinal edema formation by 48% and 70%, respectively. These observations demonstrate that antibodies directed against adhesion molecules on the neutrophil (CD18) or the vascular endothelial cell (ELAM-1) exhibit potent anti-inflammatory effects, resulting in a striking amelioration of injury in EPE in rats.

  6. Role of Adhesion Molecules in Eosinophil Activation: A Comparative Study on the Effect of Adhesion Molecules on Eosinophil Survival

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    Kazutoshi Yamaguchi

    2004-01-01

    Conclusions: The regulation of adhesion molecules, by not only preventing eosinophil adhesion but also eosinophil activation, may be a potential target in the treatment of allergic inflammatory disorders.

  7. Systemic Inflammatory Response and Adhesion Molecules

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    L. V. Molchanova

    2005-01-01

    Full Text Available The lecture presents the materials of foreign studies on the mechanisms responsible for the formation of a systemic inflammatory response syndrome (SIRS. The hypotheses accounting for the occurrence of SIRS in emergencies are described. Adhesion molecules (AM and endothelial dysfunction are apparent to be involved in the inflammatory process, no matter what the causes of SIRS are. The current classification of AM and adhesion cascades with altered blood flow is presented. There are two lines in the studies of AM. One line is to measure the concentration of AM in the plasma of patients with emergencies of various etiology. The other is to study the impact of antiadhesion therapy on the alleviation of the severity of terminal state and its outcome. The studies provide evidence for that an adhesive process is a peculiar prelude to a systemic inflammatory response.

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

    DEFF Research Database (Denmark)

    Halberg, Kenneth Agerlin; Rainey, Stephanie M.; Veland, Iben Rønn

    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....

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

    NARCIS (Netherlands)

    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.

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

    NARCIS (Netherlands)

    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

  11. Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1/CD31): A Multifunctional Vascular Cell Adhesion Molecule.

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    Delisser, H M; Baldwin, H S; Albelda, S M

    1997-08-01

    PECAM-1/CD31 is a member of the immunoglobulin gene superfamily found on platelets, leukocytes, and endothelial cells, where it concentrates at cell-cell borders. It has been shown to both mediate cell-cell adhesion through homophilic and heterophilic interactions and to transduce intracellular signals that upregulate the function of integrins on leukocytes. Its cellular distribution and ability to mediate adhesive and signaling phenomena suggested that PECAM-1 was a multifunctional vascular cell adhesion molecule involved in leukocyte-endothelial and endothelial-endothelial interactions. These initial suggestions have been largely confirmed as recent studies have implicated PECAM-1 in the inflammatory process and in the formation of blood vessels. As our understanding of the molecular and functional properties of PECAM-1 grows, new insights will be gained that may have therapeutic implications for cardiovascular development and disease. (Trends Cardiovasc Med 1997;7:203-210). © 1997, Elsevier Science Inc.

  12. Circulating adhesion molecules in obstructive sleep apnea and cardiovascular disease.

    Science.gov (United States)

    Pak, Victoria M; Grandner, Michael A; Pack, Allan I

    2014-02-01

    Over 20 years of evidence indicates a strong association between obstructive sleep apnea (OSA) and cardiovascular disease. Although inflammatory processes have been heavily implicated as an important link between the two, the mechanism for this has not been conclusively established. Atherosclerosis may be one of the mechanisms linking OSA to cardiovascular morbidity. This review addresses the role of circulating adhesion molecules in patients with OSA, and how these may be part of the link between cardiovascular disease and OSA. There is evidence for the role of adhesion molecules in cardiovascular disease risk. Some studies, albeit with small sample sizes, also show higher levels of adhesion molecules in patients with OSA compared to controls. There are also studies that show that levels of adhesion molecules diminish with continuous positive airway pressure therapy. Limitations of these studies include small sample sizes, cross-sectional sampling, and inconsistent control for confounding variables known to influence adhesion molecule levels. There are potential novel therapies to reduce circulating adhesion molecules in patients with OSA to diminish cardiovascular disease. Understanding the role of cell adhesion molecules generated in OSA will help elucidate one mechanistic link to cardiovascular disease in patients with OSA.

  13. Yielding elastic tethers stabilize robust cell adhesion.

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    Matt J Whitfield

    2014-12-01

    Full Text Available Many bacteria and eukaryotic cells express adhesive proteins at the end of tethers that elongate reversibly at constant or near constant force, which we refer to as yielding elasticity. Here we address the function of yielding elastic adhesive tethers with Escherichia coli bacteria as a model for cell adhesion, using a combination of experiments and simulations. The adhesive bond kinetics and tether elasticity was modeled in the simulations with realistic biophysical models that were fit to new and previously published single molecule force spectroscopy data. The simulations were validated by comparison to experiments measuring the adhesive behavior of E. coli in flowing fluid. Analysis of the simulations demonstrated that yielding elasticity is required for the bacteria to remain bound in high and variable flow conditions, because it allows the force to be distributed evenly between multiple bonds. In contrast, strain-hardening and linear elastic tethers concentrate force on the most vulnerable bonds, which leads to failure of the entire adhesive contact. Load distribution is especially important to noncovalent receptor-ligand bonds, because they become exponentially shorter lived at higher force above a critical force, even if they form catch bonds. The advantage of yielding is likely to extend to any blood cells or pathogens adhering in flow, or to any situation where bonds are stretched unequally due to surface roughness, unequal native bond lengths, or conditions that act to unzip the bonds.

  14. Angiogenic Effect of Intercellular Adhesion Molecule-1

    Institute of Scientific and Technical Information of China (English)

    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

  15. Adhesion Molecules: Master Controllers of the Circulatory System.

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    Schmidt, Eric P; Kuebler, Wolfgang M; Lee, Warren L; Downey, Gregory P

    2016-03-15

    This manuscript will review our current understanding of cellular adhesion molecules (CAMs) relevant to the circulatory system, their physiological role in control of vascular homeostasis, innate and adaptive immune responses, and their importance in pathophysiological (disease) processes such as acute lung injury, atherosclerosis, and pulmonary hypertension. This is a complex and rapidly changing area of research that is incompletely understood. By design, we will begin with a brief overview of the structure and classification of the major groups of adhesion molecules and their physiological functions including cellular adhesion and signaling. The role of specific CAMs in the process of platelet aggregation and hemostasis and leukocyte adhesion and transendothelial migration will be reviewed as examples of the complex and cooperative interplay between CAMs during physiological and pathophysiological processes. The role of the endothelial glycocalyx and the glycobiology of this complex system related to inflammatory states such as sepsis will be reviewed. We will then focus on the role of adhesion molecules in the pathogenesis of specific disease processes involving the lungs and cardiovascular system. The potential of targeting adhesion molecules in the treatment of immune and inflammatory diseases will be highlighted in the relevant sections throughout the manuscript.

  16. An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis.

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    Dong, Xintong; Liu, Oliver W; Howell, Audrey S; Shen, Kang

    2013-10-10

    Robust dendrite morphogenesis is a critical step in the development of reproducible neural circuits. However, little is known about the extracellular cues that pattern complex dendrite morphologies. In the model nematode Caenorhabditis elegans, the sensory neuron PVD establishes stereotypical, highly branched dendrite morphology. Here, we report the identification of a tripartite ligand-receptor complex of membrane adhesion molecules that is both necessary and sufficient to instruct spatially restricted growth and branching of PVD dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations in the surrounding hypodermal tissue, whereas DMA-1 acts as the cognate receptor on PVD. Mutations in this complex lead to dramatic defects in the formation, stabilization, and organization of the dendritic arbor. Ectopic expression of SAX-7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a DMA-1-dependent manner. Both in vivo and in vitro experiments indicate that all three molecules are needed for interaction.

  17. Adhesion molecules in breast carcinoma: a challenge to the pathologist

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    Claudia Rossetti

    2015-02-01

    Full Text Available The role of adhesion molecules is very important both in the activation of carcinogenesis and in the differentiation of subtypes of breast carcinoma, aiding in diagnosis, prognosis and therapeutic choice in these tumors. Therefore, understanding the functions and interrelationships among these molecules is crucial to the pathologist, who often uses these factors as a resource to differentiate tumors and further classify them according to a molecular point of view. Our goal is to describe the applicability and the difficulties encountered by the pathologist in the diagnosis of breast carcinoma, discussing the most commonly used markers of adhesion in routine analyses.

  18. Role of adhesion molecules in mobilization of hematopoietic cells

    Institute of Scientific and Technical Information of China (English)

    陈彤; 谢毅

    2003-01-01

    Objective To study the changes of adhesion molecules' expressions during the recombinant human granulocyte-colony-stimulating factor (rhG-CSF) mobilization in periphera l blood stem cell transplantation (PBSCT), and to confirm the influence of rhG- CSF on hematopoietic stem cells, which are proposed to guide mobilization in PBS CT. Methods Mice were injected subcutaneously with diluted rhG-CSF or normal saline for 7 days. The blood Sca-1+ stem cell count and bone marrow (BM) nucleated cell count were enumerated. The expressions of CD49d and CD44 and the adhesive ability of mononuclear cells to bone marrow matrix (fibronectin) were examined by flow c ytometry and 51Cr adhesive assay, respectively.Results The mobilizing effect of rhG-CSF on mice was the same as on humans. The number of Sca-1+ cells in peripheral blood reached the peak on the seventh day, the BM nucleated cell count was reduced, and the expressions of CD49d and the cells ' adhesive ability in BM and PB declined. Conclusions rhG-CSF can reduce some cell adhesion molecules' expressions and the adhesive a bility of hematopoietic stem cells to BM matrix, therefore mobilizing hematopoie tic stem cells (HSC) from the BM to the peripheral blood.

  19. Investigating single molecule adhesion by atomic force spectroscopy.

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    Stetter, Frank W S; Kienle, Sandra; Krysiak, Stefanie; Hugel, Thorsten

    2015-02-27

    Atomic force spectroscopy is an ideal tool to study molecules at surfaces and interfaces. An experimental protocol to couple a large variety of single molecules covalently onto an AFM tip is presented. At the same time the AFM tip is passivated to prevent unspecific interactions between the tip and the substrate, which is a prerequisite to study single molecules attached to the AFM tip. Analyses to determine the adhesion force, the adhesion length, and the free energy of these molecules on solid surfaces and bio-interfaces are shortly presented and external references for further reading are provided. Example molecules are the poly(amino acid) polytyrosine, the graft polymer PI-g-PS and the phospholipid POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine). These molecules are desorbed from different surfaces like CH3-SAMs, hydrogen terminated diamond and supported lipid bilayers under various solvent conditions. Finally, the advantages of force spectroscopic single molecule experiments are discussed including means to decide if truly a single molecule has been studied in the experiment.

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

    DEFF Research Database (Denmark)

    Nielsen, Janne; Kulahin, Nikolaj; Walmod, Peter

    2008-01-01

    Cell adhesion molecules (CAMs) mediate cell-to-cell interactions and interactions between cells and the extracellular matrix (ECM). The neural cell adhesion molecule (NCAM), a prototypic member of the immunoglobulin (Ig) superfamily of CAMs, mediates adhesion through homophilic and heterophilic i...

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

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    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.

  2. Syntenin-1 and ezrin proteins link activated leukocyte cell adhesion molecule to the actin cytoskeleton

    NARCIS (Netherlands)

    Tudor, C.; Riet, J. te; Eich, C.; Harkes, R.; Smisdom, N.; Bouhuijzen-Wenger, J.; Ameloot, M.; Holt, M.; Kanger, J.S.; Figdor, C.G.; Cambi, A.; Subramaniam, V.

    2014-01-01

    Activated leukocyte cell adhesion molecule (ALCAM) is a type I transmembrane protein member of the immunoglobulin superfamily of cell adhesion molecules. Involved in important pathophysiological processes such as the immune response, cancer metastasis, and neuronal development, ALCAM undergoes both

  3. EXPRESSION OF ADHESION MOLECULES ON PERIPHERAL BLOOD MONOCYTES DURING PREGNANCY

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    V. A. Mikhaylova

    2010-01-01

    Full Text Available Peripheral blood monocytes play a key role in regulation of immune response during pregnancy. Intensive adhesion of monocytes to endothelium proves that monocytes are activated during pregnancy. To determine a potential role of adhesion molecules for ability of monocytes to adhere, we studied expression of CD11a, CD11b, CD11c, CD18, CD49d, CD29 markers of monocytes from non-pregnant and pregnant women. Expression of adhesion molecules on monocytes was analyzed by flow cytometry. The amounts of CD11b-expressing monocytes increased during pregnancy, as compared with non-pregnant women. Intensity of CD11a, CD11b, CD11c, CD29 expression on the monocytes did also increase at normal pregnancy. These results suggest that intense adhesion of monocytes to endothelium during uncomplicated pregnancy may be determined by increased expression of CD11a, CD11b, CD11c, CD29, and higher amounts of CD11b+ monocytes.

  4. Growth hormone increases vascular cell adhesion molecule 1 expression

    DEFF Research Database (Denmark)

    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 treatment, compared with placebo [net difference between groups 151.8 microg/liter (95...

  5. Air Pollution, Obesity, Genes, and Cellular Adhesion Molecules

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    Madrigano, Jaime; Baccarelli, Andrea; Wright, Robert O.; Suh, Helen; Sparrow, David; Vokonas, Pantel S.; Schwartz, Joel

    2011-01-01

    Objectives Particulate matter (PM) has been associated with acute cardiovascular outcomes, but our understanding of the mechanism is incomplete. We examined the association between PM and cell adhesion molecules. We also investigated the modifying effect of genotype and phenotype variation to gain insight into the relevant biological pathways for this association. Methods We used mixed regression models to examine the association of PM2.5 and black carbon (BC) with serum concentrations of soluble Intercellular Adhesion Molecule (sICAM-1) and soluble Vascular Cell Adhesion Molecule (sVCAM-1), markers of endothelial function and inflammation, in a longitudinal study of 809 participants in the Normative Aging Study (1819 total observations). We also examined whether this association was modified by genotype, obesity, or diabetes status. Genes selected for analyses were either related to oxidative stress, endothelial function, lipid metabolism or metal processing. Results BC during the 2 days prior to blood draw was significantly associated with increased sVCAM-1 (4.5% increase per 1μg/m3 95% CI 1.1, 8.0). Neither pollutant was associated with sICAM-1. Larger effects of BCon sVCAM were seen in subjects with obesity (p=0.007) and who were GSTM1 null (p=0.02). Conclusions BC is associated with markers of endothelial function and inflammation. Genes related to oxidative defense may modify this association. PMID:19884647

  6. The role of adhesive molecules in endometrial cancer: part I

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    Michał Wojciechowski

    2010-10-01

    Full Text Available The carcinogenesis is a result of both functional and structural disorders in the tissue. It initiates as a mutation in a gene encoding protein that is essential for cellular function. The subsequent cascade of events leads to accumulation of mutations and loss of cellular function. The cell loses its tissue-specific morphology, disconnects from other cells and extracellular matrix and migrates – the invasion begins. It is now clear that adhesive molecules are a key player in this cascade. These proteins of the cell membrane surface are responsible for attachment of the cells to each other and to the extracellular matrix. These interactions are crucial for both structural and functional tissue organization. Lack of this homeostasis destroys the tissue architecture, impairs its function and results in invasion. Abnormal expression of adhesive molecules was reported in all examined cancers, including endometrial cancer.Endometrial cancer is the most common gynaecological cancer in developed countries. Although in many cases it is diagnosed and treated in early stages, and thus with good results, some patients cannot be cured. A complete knowledge of the pathogenesis of the disease will be helpful in identifying patients with negative prognostic factors, increased risk of recurrence and, perhaps, finding other therapeutic options. In the paper we are trying to sum up the up-to-date knowledge of the role of adhesive molecules in pathogenesis of endometrial cancer.

  7. Increased Expression of Intercellular Adhesion Molecule-1, Vascular Cellular Adhesion Molecule-1 and Leukocyte Common Antigen in Diabetic Rat Retina

    Institute of Scientific and Technical Information of China (English)

    Ningyan Bai; Shibo Tang; Jing Ma; Yan Luo; Shaofeng Lin

    2003-01-01

    Purpose: To understand the expression and distribution of intercellular adhesion molecule- 1(ICAM- 1),vascular cellular adhesion molecule- 1 (VCAM- 1)and CD45 (Leukocyte Common Antigen) in the control nondiabetic and various courses of diabetic rats retina. To explore the role of adhesion molecules (Ams) and the adhesion of leukocytes to vascular endothelial cells via Ams in diabetic retinopathy(DR).Methods: Sixty healthy adult male Wistar rats were randomly divided into diabetic groups(induced by Streptozotocin, STZ) and normal control groups. Rats in these two groups were further randomly divided into 3, 7, 14, 30, 90 and 180 days-group,including 5 rats respectively. The immunohistochemical studies of ICAM-1, VCAM-1 and CD45 were carried out in the retinal digest preparations or retinal paraffin sections, and the results were analyzed qualitatively, semi-quantitatively.Results: No positive reaction of VCAM-1 was found, and weak reactions of ICAM-1,CD45 were found in nondiabetic rats retina. The difference of 6 control groups had no statistical significance(P > 0.05). The increased ICAM-1 and CD45 staining pattern were detectable 3 days after diabetes induction, and a few VCAM-1 positive cells were observed in the retinal blood capillaries. The difference of diabetes and control is significant( P < 0.05).Following the course, the expressions of ICAM-1, VCAM-1 and CD45 were increasingly enhanced, reaching a peak at the 14th day.Conclusion: Increased expression of ICAM-1, VCAM-1 and leukocytes adhering and stacking in retinal capillaries are the very early events in DR. Coherence of expression and distribution of the three further accounts for it is the key point for the onset of DR that Ams mediates leukocytes adhesion and endothelial cell injury.

  8. Adiponectin Enhances Intercellular Adhesion Molecule-1 Expression and Promotes Monocyte Adhesion in Human Synovial Fibroblasts

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    Chen, Hsien-Te; Tsou, Hsi-Kai; Chen, Jui-Chieh; Shih, James Meng-Kun; Chen, Yen-Jen; Tang, Chih-Hsin

    2014-01-01

    Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPKα1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy. PMID:24667577

  9. The role of adhesive molecules in endometrial cancer: part II

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    Andrzej Malinowski

    2010-12-01

    Full Text Available The carcinogenesis is a result of both functional and structural disorders in the tissue. It initiates as a mutationin a gene encoding protein that is essential for cellular function. The subsequent cascade of eventsleads to accumulation of mutations and loss of cellular function. The cell loses its tissue-specific morphology,disconnects from other cells and extracellular matrix and migrates – the invasion begins. It is now clear thatadhesive molecules are a key player in this cascade. These proteins of the cell membrane surface are responsiblefor attachment of the cells to each other and to the extracellular matrix. These interactions are crucial forboth structural and functional tissue organization. Lack of this homeostasis destroys the tissue architectureand impairs its function and results in invasion. Abnormal expression of adhesive molecules was reported in allexamined cancers, including endometrial cancer.Endometrial cancer is the most common gynaecological cancer in developed countries. Although in many casesdiagnosed and treated in early stages, and thus with good results, some patients cannot be cured. Completeknowledge of the pathogenesis of the disease will be helpful in identifying the patients with negative prognosticfactors, increased risk of recurrence and, perhaps, to find other therapeutic options. In the paper we are trying tosum up the up-to-date knowledge of the role of adhesive molecules in pathogenesis of endometrial cancer.

  10. Adhesion Molecules Associated with Female Genital Tract Infection.

    Directory of Open Access Journals (Sweden)

    Jamal Qualai

    Full Text Available 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.

  11. Predicting the Stability of Hypervalent Molecules

    Science.gov (United States)

    Mitchell, Tracy A.; Finnocchio, Debbie; Kua, Jeremy

    2007-01-01

    An exercise is described which introduces students to using concepts in thermochemistry to predict relative stability of a hypervalent molecule. Students will compare the energies of formation for both fluoride and the hydride by calculations and they will also explore the issue of partial ionic character in polar covalent bonds.

  12. Reduced immunohistochemical expression of adhesion molecules in vitiligo skin biopsies.

    Science.gov (United States)

    Reichert Faria, Adriane; Jung, Juliana Elizabeth; Silva de Castro, Caio César; de Noronha, Lucia

    2017-03-01

    Because defects in adhesion impairment seem to be involved in the etiopathogenesis of vitiligo, this study aimed to compare the immunohistochemical expression of several adhesion molecules in the epidermis of vitiligo and non lesional vitiligo skin. Sixty-six specimens of lesional and non lesional skin from 33 volunteers with vitiligo were evaluated by immunohistochemistry using anti-beta-catenin, anti-E-cadherin, anti-laminin, anti-beta1 integrin, anti-collagen IV, anti-ICAM-1 and anti-VCAM-1 antibodies. Biopsies of vitiligo skin demonstrated a significant reduction in the expression of laminin and integrin. The average value of the immunohistochemically positive reaction area of the vitiligo specimens was 3053.2μm(2), compared with the observed value of 3431.8μm(2) in non vitiligo skin (p=0.003) for laminin. The immuno-positive area was 7174.6μm(2) (vitiligo) and 8966.7μm(2) (non lesional skin) for integrin (p=0.042). A reduction in ICAM-1 and VCAM-1 expression in the basal layer of the epidermis in vitiligo samples was also observed (p=0.001 and pskin. Our results suggest that an impairment in adhesion exists in vitiligo skin, which is supported by the diminished immunohistochemical expression of laminin, beta1 integrin, ICAM-1 and VCAM-1.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  14. Exenatide Alters Gene Expression of Neural Cell Adhesion Molecule (NCAM), Intercellular Cell Adhesion Molecule (ICAM), and Vascular Cell Adhesion Molecule (VCAM) in the Hippocampus of Type 2 Diabetic Model Mice

    Science.gov (United States)

    Gumuslu, Esen; Cine, Naci; Gökbayrak, Merve Ertan; Mutlu, Oguz; Celikyurt, Ipek Komsuoglu; Ulak, Guner

    2016-01-01

    Background Glucagon-like peptide-1 (GLP-1), a potent and selective agonist for the GLP-1 receptor, ameliorates the symptoms of diabetes through stimulation of insulin secretion. Exenatide is a potent and selective agonist for the GLP-1 receptor. Cell adhesion molecules are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. Material/Methods The present study demonstrated the effects of exenatide treatment (0.1 μg/kg, subcutaneously, twice daily for 2 weeks) on the gene expression levels of cell adhesion molecules, neural cell adhesion molecule (NCAM), intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) in the brain tissue of diabetic BALB/c male mice by real-time quantitative polymerase chain reaction (PCR). Diabetes was induced by streptozotocin/nicotinamide (STZ-NA) injection to male mice. Results The results of this study revealed that hippocampal gene expression of NCAM, ICAM, and VCAM were found to be up-regulated in STZ-NA-induced diabetic mice compared to those of controls. A significant decrease in the gene expression levels of NCAM, ICAM, and VCAM were determined after 2 weeks of exenatide administration. Conclusions Cell adhesion molecules may be involved in the molecular mechanism of diabetes. Exenatide has a strong beneficial action in managing diabetes induced by STZ/NA by altering gene expression of NCAM, ICAM, and VCAM. PMID:27465247

  15. Changes in cell adhesion molecule expression on T cells associated with systemic virus infection

    DEFF Research Database (Denmark)

    Andersson, E C; Christensen, Jan Pravsgaard; Marker, O

    1994-01-01

    Virus-induced changes in adhesion molecule expression on T cells were investigated to understand how antiviral effector cells migrate into infectious foci. FACS analysis revealed that after systemic infection with lymphocytic choriomeningitis virus a number of cell adhesion molecules, including VLA...... analyses showed that T cells with a changed adhesion molecule profile tended to present other cell surface markers indicating a state of cellular activation, e.g., IL-2R, and included all virus-specific CTL effectors. Regarding the physiologic significance of these changes in adhesion molecule expression...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Development of Capsular Adhesive Systems and Evaluation of Their Stability.

    Science.gov (United States)

    1985-07-26

    AD-A159 913 DEVELOPMENT OF CAPSULAR ADHESIVE SYSTEMS AND EVALUATION ii OF THEIR STABILIT..(I) INSTITUTO NACIONAL OE TECNICA AEROESPACIRL MADRID...by polymerization of some low molecular monomeric consti- tuents, partially solubilized in the aqueous phase. The hazy liquid was discarded by...incomplete solubility of Loctite 270, it is assumed that the insoluble portion of this adhesive 5 concerns the high molecular polymeric constituent, inclu

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

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Walmod, Peter

    2008-01-01

    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 ...

  19. Intercellular adhesion molecule-1 mediates murine colon adenocarcinoma invasion.

    Science.gov (United States)

    Howard, Kenton; Lo, Karen K; Ao, Lihua; Gamboni, Fabia; Edil, Barish H; Schulick, Richard; Barnett, Carlton C

    2014-03-01

    Intercellular adhesion molecule-1 (ICAM-1) modulates cell-cell adhesion and is a receptor for cognate ligands on leukocytes. Upregulation of ICAM-1 has been demonstrated in malignant transformation of adenomas and is associated with poor prognosis for many malignancies. ICAM-1 is upregulated on the invasive front of pancreatic metastases and melanomas. These data suggest that the upregulated ICAM-1 expression promotes malignant progression. We hypothesize that the downregulation of ICAM-1 will mitigate tumor progression. Mouse colon adenocarcinoma cells (MC38) were evaluated for the expression of ICAM-1 using Western immunoblot analysis. Short hairpin RNA (shRNA) transduction was used to downregulate ICAM-1. Tumor invasion determined via a modified Boyden chamber was used as a surrogate of tumor progression examining MC38 cells, MC38 ICAM-1 knockdowns, and MC38 transduced with vehicle control. The cells were cultured in full media for 24 h and serum-starved for 24 h. A total of 5 × 10(4) cells were plated and allowed to migrate for 24 h using full media with 10% fetal bovine serum as a chemoattractant. Inserts were fixed and stained with crystal violet. Blinded investigators counted the cells using a stereomicroscope. Statistical analysis was performed by analysis of variance with Fischer protected least significant difference and a P value of 45% (P < 0.03). There were no significant differences between the invasion rates of MC38 and MC38 vehicle controls. Downregulation of ICAM-1 mitigates MC38 invasion. These data suggest that targeted downregulation of tumor ICAM-1 is a potential therapeutic target. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Cerebrospinal fluid and plasma concentration of soluble intercellular adhesion molecule1, vascular cell adhesion molecule1 and endothelial leukocyte adhesion molecule in patients with acute ischemic b

    Directory of Open Access Journals (Sweden)

    Selaković Vesna M.

    2003-01-01

    Full Text Available Background. Leukocyte migration into the ischemic area is a complex process controlled by adhesion molecules (AM in leukocytes and endothelium, by migratory capacity of leukocytes and the presence of hemotaxic agents in the tissue. In this research it was supposed that in the blood and cerebrospinal fluid (CSF of patients in the acute phase of ischemic brain disease (IBD there were relevant changes in the concentration of soluble AM (sICAM-1 sVCAM-1 and sE-selectin, that could have been the indicators of the intensity of damaging processes in central nervous system (CNS. Methods. The study included 45 IBD patients, 15 with transient ischemic attack (TIA 15 with reversible ischemic attack (RIA, and 15 with brain infarction (BI of both sexes, mean age 66±7. Control group consisted of 15 patients with radicular lesions of discal origin, subjected to diagnostic radiculography without the signs of interruption in the passage of CSF. Changes of selected biochemical parameters were determined in all patients in frame 72 hours since the occurence of an ischemic episode. Concentrations of soluble AM were determined in plasma and CSF by ELISA. Total number of leukocytes (TNL in peripheral blood was determined by hematological analyzer. Results. The results showed that during the first 72 hrs of IBD significant increases occured in TNL and that the increase was progressive compared to the severeness of the disease. Significant increase of soluble AM concentration was shown in plasma of IBD patients. The increase was highest in BI somewhat lower in RIA and the lowest in TIA patients compared to the control. In CSF concentrations of sICAM-1, sVCAM-1 and sE-selectin demonstrated similar increasing trend as in plasma. Conclusion. TNL, as well as the soluble AM concentrations in plasma and CSF, were increased during the acute IBD phase and progressive in relation to the severeness of the disease, so that they might have been the indicators of CNS inflammatory

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

    DEFF Research Database (Denmark)

    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...

  2. Hydrolytic stability of self-etch adhesives bonded to dentin.

    Science.gov (United States)

    Inoue, S; Koshiro, K; Yoshida, Y; De Munck, J; Nagakane, K; Suzuki, K; Sano, H; Van Meerbeek, B

    2005-12-01

    Functional monomers chemically interact with hydroxyapatite that remains within submicron hybrid layers produced by mild self-etch adhesives. The functional monomer 10-MDP interacts most intensively with hydroxyapatite, and its calcium salt appeared most hydrolytically stable, as compared with 4-MET and phenyl-P. We investigated the hypothesis that additional chemical interaction of self-etch adhesives improves bond stability. The micro-tensile bond strength (muTBS) of the 10-MDP-based adhesive did not decrease significantly after 100,000 cycles, but did after 50,000 and 30,000 cycles, respectively, for the 4-MET-based and the phenyl-P-based adhesives. Likewise, the interfacial ultrastructure was unchanged after 100,000 thermocycles for the 10-MDP-based adhesive, while that of both the 4-MET- and phenyl-P-based adhesives contained voids and less-defined collagen. The findings of this study support the concept that long-term durability of adhesive-dentin bonds depends on the chemical bonding potential of the functional monomer.

  3. Dental adhesion review: aging and stability of the bonded interface.

    Science.gov (United States)

    Breschi, Lorenzo; Mazzoni, Annalisa; Ruggeri, Alessandra; Cadenaro, Milena; Di Lenarda, Roberto; De Stefano Dorigo, Elettra

    2008-01-01

    Most of current dental adhesive systems show favorable immediate results in terms of retention and sealing of bonded interface, thereby counteracting polymerization shrinkage that affects resin-based restorative materials. Despite immediate efficacy, there are major concerns when dentin bonded interfaces are tested after aging even for short time period, i.e. 6 months. This study critically discusses the latest peer-reviewed reports related to formation, aging and stability of resin bonding, focusing on the micro and nano-phenomena related to adhesive interface degradation. Most simplified one-step adhesives were shown to be the least durable, while three-step etch-and-rinse and two-step self-etch adhesives continue to show the highest performances, as reported in the overwhelming majority of studies. In other words, a simplification of clinical application procedures is done to the detriment of bonding efficacy. Among the different aging phenomena occurring at the dentin bonded interfaces, some are considered pivotal in degrading the hybrid layer, particularly if simplified adhesives are used. Insufficient resin impregnation of dentin, high permeability of the bonded interface, sub-optimal polymerization, phase separation and activation of endogenous collagenolytic enzymes are some of the recently reported factors that reduce the longevity of the bonded interface. In order to overcome these problems, recent studies indicated that (1) resin impregnation techniques should be improved, particularly for two-step etch-and-rinse adhesives; (2) the use of conventional multi-step adhesives is recommended, since they involve the use of a hydrophobic coating of nonsolvated resin; (3) extended curing time should be considered to reduce permeability and allow a better polymerization of the adhesive film; (4) proteases inhibitors as additional primer should be used to increase the stability of the collagens fibrils within the hybrid layer inhibiting the intrinsic

  4. Matrix metalloproteinase inhibitory properties of benzalkonium chloride stabilizes adhesive interfaces.

    Science.gov (United States)

    Sabatini, Camila; Patel, Shaival K

    2013-12-01

    This study evaluated the effects of different concentrations of benzalkonium chloride (BAC) on the preservation of adhesive interfaces created with two etch-and-rinse adhesives and its inhibitory properties on dentin matrix metalloproteinase (MMP) activity. The following groups were tested with the adhesive systems Optibond Solo Plus and All-Bond 3: Group 1, adhesive without inhibitor (control); Group 2, topical 2.0% chlorhexidine (2.0% CHX); Group 3, phosphoric acid with 1.0%wt BAC (BAC-PA); Group 4, 0.25% BAC-adhesive (0.25% BAC); Group 5, 0.5% BAC-adhesive (0.5% BAC); Group 6, 1.0% BAC-adhesive (1.0% BAC); and Group 7, 2.0% BAC-adhesive (2.0% BAC). Composite cylinders were fabricated, and shear bond strength (SBS) was evaluated after 24 h, 6 months, and 18 months of storage. Extracts from concentrated demineralized human dentin powder were subjected to SDS-PAGE and incubated in the presence of 0.25, 0.5, 1.0, and 2.0% BAC. Overall, stable bonds were maintained for 18 months. Improved bond strengths were seen for 0.5% BAC and 1.0% BAC when bonding with Optibond Solo Plus, and for 0.25% BAC and 0.5% BAC when bonding with All-Bond 3. Zymographic analysis revealed complete inhibition of gelatinolytic activity with BAC. Benzalkonium chloride, at all concentrations, inhibited dentin proteolytic activity, which seems to have contributed to the improved bond stability after 18 months for specific combinations of BAC concentration and adhesive.

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

    Directory of Open Access Journals (Sweden)

    Ji Won Um

    2014-03-01

    Full Text Available 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 is highly expressed during various postnatal periods of mouse brain development. The simultaneous knockdown of all three CSTs, but not CST-3 alone, decreases inhibitory, but not excitatory, synapse densities in cultured hippocampal neurons. Moreover, the knockdown of CSTs specifically reduces inhibitory synaptic transmission in vitro and in vivo. Remarkably, the loss of CSTs induces a concomitant decrease in neuron soma size in a non-cell-autonomous manner. Furthermore, α-neurexins (α-Nrxs are components of a CST-3 complex involved in CST-3-mediated presynaptic differentiation. However, CST-3 does not directly bind to Nrxs. Viewed together, these data suggest that the three CSTs redundantly regulate inhibitory synapse formation, inhibitory synapse function, and neuron development in concert with Nrxs.

  6. Current aspects on bonding effectiveness and stability in adhesive dentistry.

    Science.gov (United States)

    Cardoso, M V; de Almeida Neves, A; Mine, A; Coutinho, E; Van Landuyt, K; De Munck, J; Van Meerbeek, B

    2011-06-01

    Improved dental adhesive technology has extensively influenced modern concepts in restorative dentistry. In light of minimal-invasive dentistry, this new approach promotes a more conservative cavity design, which basically relies on the effectiveness of current enamel-dentine adhesives. Nowadays, the interaction of adhesives with the dental substrate is based on two different strategies, commonly described as an etch-and-rinse and a self-etch approach. In an attempt to simplify the bonding technique, manufacturers have decreased the number of steps necessary for the accomplishment of the bonding procedure. As a consequence, two-step etch-and-rinse and one-step (self-etch) adhesives were introduced and gained rapid popularity in the dental market due to their claimed user-friendliness and lower technique sensitivity. However, many concerns have been raised on the bonding effectiveness of these simplified adhesives, especially in terms of durability, although this tends to be very material dependent. In order to blend all the adhesive components into one single solution, one-step adhesives were made more acidic and hydrophilic. Unfortunately, these properties induce a wide variety of seemingly unrelated problems that may jeopardize the effectiveness and stability of adhesion to the dental substrate. Being more susceptible to water sorption and thus nanoleakage, these adhesives are more prone to bond degradation and tend to fail prematurely as compared to their multi-step counterparts. Incidentally, another factor that may interfere with the bonding effectiveness of adhesives is the technique used for caries removal and cavity preparation. Several tools are on the market today to effectively remove carious tissue, thereby respecting the current trend of minimum intervention. Despite their promising performance, such techniques modify the tooth substrate in different aspects, possibly affecting bonding effectiveness. Altogether, we may conclude that not only the

  7. The in vitro effect of desflurane preconditioning on endothelial adhesion molecules and mRNA expression.

    Science.gov (United States)

    Biao, Zhu; Zhanggang, Xue; Hao, Jiang; Changhong, Miao; Jing, Cang

    2005-04-01

    Lower expression of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin may be responsible for attenuated ischemic-reperfusion neutrophil adhesion to vascular endothelium. Desflurane reduces ischemia-reperfusion injury. Therefore, we assessed whether desflurane affects the protein expression of ICAM-1 and E-selectin and mRNA expression of ICAM-1 and VCAM-1 of human umbilical venous endothelial cells (HUVEC) stimulated with tumor necrosis factor-alpha (TNF-alpha). HUVEC were preconditioned for 60 min with 1 minimum alveolar concentration desflurane before stimulating with TNF-alpha. Protein expression of adhesion molecules ICAM-1 and E-selectin of HUVEC were evaluated via immunocytochemical techniques combined with image cytometry. ICAM-1 and VCAM-1 mRNA expression of HUVEC were determined via reverse transcription-polymerase chain reaction. Desflurane not only reduced the protein expression of ICAM-1 and E-selectin but also ICAM-1 and VCAM-1 mRNA expression of the HUVEC. The adhesion rate of neutrophils with desflurane-treated HUVEC was slower. The decreased neutrophil adhesion on the desflurane-treated HUVEC correlated well with the decrease in adhesion molecule expression. These results show that desflurane affects the expression of adhesion molecules involved in the multistep process of neutrophil recruitment. Desflurane related ischemia-reperfusion injury reduction correlates well with expression inhibition of ICAM-1, VCAM-1, and E-selectin that mediates neutrophil rotation and firm adhesion on the vascular endothelium.

  8. The talin head domain reinforces integrin-mediated adhesion by promoting adhesion complex stability and clustering.

    Directory of Open Access Journals (Sweden)

    Stephanie J Ellis

    2014-11-01

    Full Text Available Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex. In addition, the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands, a process known as inside-out activation. We previously showed that in Drosophila, mutating the integrin binding site in the talin head domain resulted in weakened adhesion to the ECM. Intriguingly, subsequent studies showed that canonical inside-out activation of integrin might not take place in flies. Consistent with this, a mutation in talin that specifically blocks its ability to activate mammalian integrins does not significantly impinge on talin function during fly development. Here, we describe results suggesting that the talin head domain reinforces and stabilizes the integrin adhesion complex by promoting integrin clustering distinct from its ability to support inside-out activation. Specifically, we show that an allele of talin containing a mutation that disrupts intramolecular interactions within the talin head attenuates the assembly and reinforcement of the integrin adhesion complex. Importantly, we provide evidence that this mutation blocks integrin clustering in vivo. We propose that the talin head domain is essential for regulating integrin avidity in Drosophila and that this is crucial for integrin-mediated adhesion during animal development.

  9. Radiolytic and hydrolytic stability of extractant molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cames, B.; Caniffi, B.; Rudloff, D. [CEA Marcoule - DRCP/SCPS/LCSE: BP 17171, Bagnols-sur-Ceze, 30207 cedex (France)

    2008-07-01

    In nuclear spent fuel reprocessing industry, actinide partitioning processes are based on solvent extraction and organic phase recycling. It is well-known that both radiolysis and acidic hydrolysis leads to degradation of extractant molecules. To have more information on the stability of extractant molecules used in a reprocessing plant, batch studies have been carried out to determine parameters governing the extractant consumption kinetic under hydrolysis and radiolysis effects (dose rate, degradation time and nitric acidity of the organic phase). For gamma radiation, results about DMDOHEMA (N,N'-dimethyl-N,N'-di-octyl-hexyl-ethoxy-malonamide) and DEHiBA (N,N'-di(ethyl-2-hexyl)iso-butanamide) show that degradation of DMDOHEMA and DEHiBA depends only on nitric acidity of the organic phase, dose rate and radiolysis time (DMDOHEMA consumption kinetic constant is 2 times slower than for DEHiBA). For same degradation conditions, it has been shown that {alpha}-radiolysis of DMDOHEMA is 4 times slower than {gamma}-radiolysis, and acidic hydrolysis of DMDOHEMA is effective whereas that of DEHiBA is not. (authors)

  10. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Rudenko, Gabby (Texas-MED)

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Adhesion molecules and the extracellular matrix as drug targets for glioma.

    Science.gov (United States)

    Shimizu, Toshihiko; Kurozumi, Kazuhiko; Ishida, Joji; Ichikawa, Tomotsugu; Date, Isao

    2016-04-01

    The formation of tumor vasculature and cell invasion along white matter tracts have pivotal roles in the development and progression of glioma. A better understanding of the mechanisms of angiogenesis and invasion in glioma will aid the development of novel therapeutic strategies. The processes of angiogenesis and invasion cause the production of an array of adhesion molecules and extracellular matrix (ECM) components. This review focuses on the role of adhesion molecules and the ECM in malignant glioma. The results of clinical trials using drugs targeted against adhesion molecules and the ECM for glioma are also discussed.

  13. Cytokine and adhesion molecule expression evolves between the neutrophilic and lymphocytic phases of viral meningitis.

    Science.gov (United States)

    Makis, Alexandros; Shipway, David; Hatzimichael, Eleftheria; Galanakis, Emmanouil; Pshezhetskiy, Dmitry; Chaliasos, Nikolaos; Stebbing, Justin; Siamopoulou, Antigone

    2010-09-01

    Viral meningitis is characterized by cerebrospinal fluid (CSF) lymphocyte pleocytosis, although neutrophils may predominate in the early phase. The T helper 1 (Th1)/Th2 cytokine balance and expression of adhesion molecules seem to be involved in the CSF chemotaxis. We aimed to determine expression of cytokines and adhesion molecules in enteroviral meningitis. We investigated the serum and CSF levels of adhesion molecules (E-selectin, L-selectin, vascular cell adhesion molecule-1 [VCAM-1], and intracellular adhesion molecule-1 [ICAM-1]) and cytokines (interleukin-12 [IL-12] and IL-4) in 105 children during an outbreak of enteroviral meningitis. Diagnosis was confirmed with positive polymerase chain reaction (PCR) and/or serology for echovirus or Coxsackie virus, and matched with control subjects for clinical features but with negative PCR and/or serology. Apart from VCAM-1, the CSF levels of all investigated inflammatory molecules were significantly increased. In serum, sL-selectin and ICAM-1 levels were significantly higher than control subjects. Serum and CSF L-selectin, serum VCAM-1, and CSF IL-12 were all observed to be expressed in significantly higher levels in the neutrophil-dominant subgroup (72% had duration of symptoms 24 h). Serum and CSF ICAM-1 was found at significantly higher levels in the latter group. Evolving expression of adhesion molecules and cytokines indicates a shift from Th1 to Th2 immune responses as infection progresses.

  14. Stability of focal adhesion enhanced by its inner force fluctuation

    Science.gov (United States)

    Mao, Zhi-Xiu; Chen, Xiao-Feng; Chen, Bin

    2015-08-01

    Cells actively sense and respond to mechanical signals from the extracellular matrix through focal adhesions. By representing a single focal adhesion as a cluster of slip bonds, it has been demonstrated that the cluster often became unstable under fluctuated forces. However, an unusual case was also reported, where the stability of the cluster might be substantially enhanced by a fluctuated force with a relatively low fluctuation frequency and high fluctuation amplitude. Such an observation cannot be explained by the conventional fracture theory of fatigue. Here, we intensively investigate this intriguing observation by carrying out systematic parametric studies. Our intensive simulation results indicate that stability enhancement of this kind is in fact quite robust, which can be affected by the stochastic features of a single bond and the profile of the fluctuated forces such as the average value of bond force. We then suggest that the fluctuation of traction force within a focal adhesion might enhance its stability in a certain way. Project supported by the National Natural Science Foundation of China (Grant No.*11372279).

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

    NARCIS (Netherlands)

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

    DEFF Research Database (Denmark)

    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...

  17. Adhesion molecules and chemokines: relation to anthropometric, body composition, biochemical and dietary variables

    OpenAIRE

    2014-01-01

    Introduction: Among the inflammatory mediators involved in the pathogenesis of obesity, the cell adhesion molecules P-selectin, E-selectin, VCAM-1, ICAM-1 and the chemokine MCP-1 stand out. They play a crucial role in adherence of cells to endothelial surfaces, in the integrity of the vascular wall and can be modulated by body composition and dietary pattern. Objectives: To describe and discuss the relation of these cell adhesion molecules and chemokines to anthropometric, body composition, d...

  18. Adhesion molecules and chemokines : relation to anthropometric, body composition, biochemical and dietary variables.

    OpenAIRE

    Vieira, Renata Adrielle Lima; Freitas,Renata Nascimento; Volp, Ana Carolina Pinheiro

    2014-01-01

    Introduction: Among the inflammatory mediators involved in the pathogenesis of obesity, the cell adhesion molecules Pselectin, E-selectin, VCAM-1, ICAM-1 and the chemokine MCP-1 stand out. They play a crucial role in adherence of cells to endothelial surfaces, in the integrity of the vascular wall and can be modulated by body composition and dietary pattern. Objectives: To describe and discuss the relation of these cell adhesion molecules and chemokines to anthropometric, body composition, di...

  19. A role for adhesion molecules in contact-dependent T help for B cells

    DEFF Research Database (Denmark)

    Owens, T

    1991-01-01

    . There was no correlation between the level of expression of adhesion molecules by T cells and their ability to induce B cell responses. Anti-LFA-1 abrogated T-dependent responses to IL2 which were inducible after 2 days in culture, but did not inhibit the induction of this IL2 responsiveness. These results suggest...... that continued cell contact involving adhesion/accessory molecules induces B cells to proliferate and to respond to T cell lymphokines. A signaling role for cell interaction molecules on B cells is proposed, similar to the role of these and analogous molecules on T cells....

  20. Immunohistochemical evaluation of endothelial cell adhesion molecules in human dental pulp: effects of tooth preparation and adhesive application.

    Science.gov (United States)

    Bagis, Bora; Atilla, Pergin; Cakar, Nur; Hasanreisoglu, Ufuk

    2007-08-01

    Studies have demonstrated that restorative procedures can initiate pulpal inflammation. Adhesion molecules on endothelial cells mediate the leukocyte-endothelium interaction, which is the fundamental event of inflammation. The aim of this study was to evaluate possible changes in the endothelial cell adhesion molecules (CAMs) of human dental pulp with tooth preparation, and after the application of one-step self-etch adhesive. Twenty healthy human premolars and third molars scheduled to be extracted for orthodontic reasons were randomly assigned to four experimental groups. Group 1 involved sound intact teeth representing the controls. In group 2, teeth were prepared for full crown and extracted within 2h. Groups 3 and 4 comprised the teeth coated with one-step self-etch adhesive, iBond Gluma inside following the preparation and extracted after 24 and 48h, respectively. Tissue distribution and staining intensity of CAMs including E-selectin, P-selectin, ICAM-1, VCAM-1 and PECAM-1 was investigated in the pulp samples using monoclonal antibodies and the streptavidin-biotin-horse-radish immunoperoxidase procedure. The assessment of immunohistochemical reactions was performed by two independent observers using a semi-quantitative scale. All the CAMs evaluated were expressed by the healthy pulp tissues. Significant alterations in the distribution and staining intensity of CAMs were detected following tooth preparation. One-step self-etch adhesive tested in the present study induced inflammatory reactions in the pulp (Padhesive on prepared teeth had a potential to interfere with the inflammatory response.

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

    DEFF Research Database (Denmark)

    Brown, Alan; Turner, Louise; Christoffersen, Stig

    2013-01-01

    . The PfEMP1 family of adhesive proteins is responsible for this sequestration by mediating interactions with diverse human ligands. In addition, as the primary targets of acquired, protective immunity, the PfEMP1s are potential vaccine candidates. PfEMP1s contain large extracellular ectodomains made from......, intercellular adhesion molecule-1 (ICAM-1). We show through small angle x-ray scattering that IT4VAR13 is rigid, elongated, and monomeric. We also show that it interacts with ICAM-1 through the DBLß domain alone, forming a 1:1 complex. These studies provide a first low resolution structural view of a PfEMP1...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  3. Modulation of adhesion molecules by cholesterol-lowering therapy in mononuclear cells from hypercholesterolemic patients.

    Science.gov (United States)

    Cerda, Alvaro; Rodrigues, Alice Cristina; Alves, Camila; Genvigir, Fabiana Dalla Vecchia; Fajardo, Cristina Moreno; Dorea, Egidio Lima; Gusukuma, Maria Cecilia; Pinto, Gelba Almeida; Hirata, Mario Hiroyuki; Hirata, Rosario Dominguez Crespo

    2015-08-01

    Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described. To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells. The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics. The effects of atorvastatin, simvastatin, and ezetimibe on mRNA and protein expression of adhesion molecules were also evaluated in THP-1 cells. Simvastatin/ezetimibe combination, but not the monotherapies, reduced the mRNA expression of the PSGL-1, LFA-1, and Mac-1 genes in PBMC from hypercholesterolemics. Total and LDL cholesterol in serum correlated with PSGL-1 mRNA expression, whereas HDL cholesterol negatively correlated with mRNA levels of L-selectin and VLA-4 genes (P molecules in PBMC from hypercholesterolemics and THP-1 cells. Simvastatin/ezetimibe combination gives more benefits by reducing to a larger extent the expression of adhesion molecules in mononuclear cells. © 2015 John Wiley & Sons Ltd.

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

    LENUS (Irish Health Repository)

    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.

  5. Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons.

    Science.gov (United States)

    Földy, Csaba; Darmanis, Spyros; Aoto, Jason; Malenka, Robert C; Quake, Stephen R; Südhof, Thomas C

    2016-08-30

    In brain, signaling mediated by cell adhesion molecules defines the identity and functional properties of synapses. The specificity of presynaptic and postsynaptic interactions that is presumably mediated by cell adhesion molecules suggests that there exists a logic that could explain neuronal connectivity at the molecular level. Despite its importance, however, the nature of such logic is poorly understood, and even basic parameters, such as the number, identity, and single-cell expression profiles of candidate synaptic cell adhesion molecules, are not known. Here, we devised a comprehensive list of genes involved in cell adhesion, and used single-cell RNA sequencing (RNAseq) to analyze their expression in electrophysiologically defined interneurons and projection neurons. We compared the cell type-specific expression of these genes with that of genes involved in transmembrane ion conductances (i.e., channels), exocytosis, and rho/rac signaling, which regulates the actin cytoskeleton. Using these data, we identified two independent, developmentally regulated networks of interacting genes encoding molecules involved in cell adhesion, exocytosis, and signal transduction. Our approach provides a framework for a presumed cell adhesion and signaling code in neurons, enables correlating electrophysiological with molecular properties of neurons, and suggests avenues toward understanding synaptic specificity.

  6. Endothelial Cell Junctional Adhesion Molecules: Role and Regulation of Expression in Inflammation.

    Science.gov (United States)

    Reglero-Real, Natalia; Colom, Bartomeu; Bodkin, Jennifer Victoria; Nourshargh, Sussan

    2016-10-01

    Endothelial cells line the lumen of all blood vessels and play a critical role in maintaining the barrier function of the vasculature. Sealing of the vessel wall between adjacent endothelial cells is facilitated by interactions involving junctionally expressed transmembrane proteins, including tight junctional molecules, such as members of the junctional adhesion molecule family, components of adherence junctions, such as VE-Cadherin, and other molecules, such as platelet endothelial cell adhesion molecule. Of importance, a growing body of evidence indicates that the expression of these molecules is regulated in a spatiotemporal manner during inflammation: responses that have significant implications for the barrier function of blood vessels against blood-borne macromolecules and transmigrating leukocytes. This review summarizes key aspects of our current understanding of the dynamics and mechanisms that regulate the expression of endothelial cells junctional molecules during inflammation and discusses the associated functional implications of such events in acute and chronic scenarios. © 2016 American Heart Association, Inc.

  7. Adhesion molecule expression stimulated by Bacteroides thetaiotaomicron cell-surface antigens.

    Science.gov (United States)

    Rokosz, A; Meisel-Mikołajczyk, F; Malchar, C; Nowaczyk, M; Górski, A

    1999-01-01

    Bacteroides thetaiotaomicron, a Gram-negative anaerobic rod belonging to the Bacteroides fragilis group (BFG), is involved in many systemic and local, most frequently suppurative infections in man. The cell envelope of these rods is composed of two carbohydrate-containing antigens: lipopolysaccharide (LPS) and capsular polysaccharide (CPS). Adhesion molecules ICAM-1, VCAM-1 and E-selectin (ELAM-1) are induced on the endothelial cells by mediators of inflammation. The aim of this study was to assay the ability of B. thetaiotaomicron surface antigens to induce adhesion molecule expression on the endothelial cells. The influence of LPS and CPS on the expression of adhesion molecules on HMEC-1 cell line was examined in an ELISA test. ELISA was performed with monoclonal mouse anti-human: ICAM-1, VCAM-1 and E-selectin antibodies of the IgG class. B. thetaiotaomicron lipopolysaccharides revealed the ability to induce ICAM-1, VCAM-1 and E-selectin expression on the endothelial cells. Their activities were similar, but lower than the activity of Eschericha coli LPS. ICAM-1 was the most stimulated adhesion molecule. The strongest activation by LPS was achieved at the concentrations of 10.0 and 1.0 micrograms/ml. The ability of capsular polysaccharide to induce the expression of adhesion molecules was considerably weaker.

  8. Single-molecule manipulation experiments to explore friction and adhesion

    Science.gov (United States)

    Pawlak, R.; Kawai, S.; Meier, T.; Glatzel, T.; Baratoff, A.; Meyer, E.

    2017-03-01

    Friction forces, which arise when two bodies that are in contact are moved with respect to one another, are ubiquitous phenomena. Although various measurement tools have been developed to study these phenomena at all length scales, such investigations are highly challenging when tackling the scale of single molecules in motion on a surface. This work reviews the recent advances in single-molecule manipulation experiments performed at low temperature with the aim of understanding the fundamental frictional response of single molecules. Following the advent of ‘nanotribology’ in the field based on the atomic force microscopy technique, we will show the technical requirements to direct those studies at the single-molecule level. We will also discuss the experimental prerequisites needed to obtain and interpret the phenomena, such as the implementation of single-molecule manipulation techniques, the processing of the experimental data or their comparison with appropriate numerical models. Finally, we will report examples of the controlled vertical and lateral manipulation of long polymeric chains, graphene nanoribbons or single porphyrin molecules that systematically reveal friction-like characteristics while sliding over atomically clean surfaces.

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

    Science.gov (United States)

    Rimpelová, Silvie; Kasálková, Nikola Slepičková; Slepička, Petr; Lemerová, Helena; Švorčík, Václav; Ruml, Tomáš

    2013-04-01

    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.

  10. Engagement of major histocompatibility complex class I and class II molecules up-regulates intercellular adhesion of human B cells via a CD11/CD18-independent mechanism.

    Science.gov (United States)

    Alcover, A; Juillard, V; Acuto, O

    1992-02-01

    We have studied the role of major histocompatibility complex (MHC) molecules in the regulation of intercellular adhesion of human B cells. We found that molecules able to bind to MHC class II molecules, such as monoclonal antibodies or staphylococcal enterotoxins, induced rapid and sustained homotypic adhesion of Epstein-Barr virus (EBV)-transformed B cell lines as well as peripheral blood B lymphocytes. Moreover, anti-MHC class I monoclonal antibodies also stimulated intercellular adherence. Adhesion induced upon MHC engagement was faster and stronger than that triggered by phorbol esters. It needed active metabolism, but divalent cations were not required. Monoclonal antibodies directed against LFA-1 (CD11a/CD18) or its ligand ICAM-1 (CD54) did not inhibit MHC class II-induced homotypic adhesion of various EBV-transformed B cell lines, nor of a variant of the B cell line Raji expressing very low LFA-1 surface levels. Moreover, EBV-transformed B cells from a severe lymphocyte adhesion deficiency patient, lacking surface CD11/CD18, also aggregated in response to anti-MHC class I or class II monoclonal antibodies. Together these data indicate that engagement of MHC molecules may transduce signals to B cells resulting in up-regulation of intercellular adhesion, via an LFA-1-independent mechanism. This may play a role in the stabilization of T cell/antigen-presenting cell conjugates at the moment of antigen recognition.

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

    Science.gov (United States)

    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 before and after the healthy life exercise program in all the subjects. [Results] After the healthy life exercise program, MCP-1 and the arteriosclerosis adhesion molecules sE-selectin and sVCAM-1 were statistically significantly decreased. [Conclusion] The 12-week healthy life exercise program reduced the levels of arteriosclerosis adhesion molecules. Therefore, the results of our study suggest that a healthy life exercise program may be useful in preventing arteriosclerosis and improving quality of life in elderly obese women. PMID:26157257

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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 cholesterol levels. In addition, 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.

  14. Pharmacology of cell adhesion molecules of the nervous system

    DEFF Research Database (Denmark)

    Kiryushko, Darya; Bock, Elisabeth; Berezin, Vladimir

    2007-01-01

    development. The majority of CAMs are signal transducing receptors. CAM-induced intracellular signalling is triggered via homophilic (CAM-CAM) and heterophilic (CAM - other counter-receptors) interactions, which both can be targeted pharmacologically. We here describe the progress in the CAM pharmacology...... focusing on cadherins and CAMs of the immunoglobulin (Ig) superfamily, such as NCAM and L1. Structural basis of CAM-mediated cell adhesion and CAM-induced signalling are outlined. Different pharmacological approaches to study functions of CAMs are presented including the use of specific antibodies......, recombinant proteins, and synthetic peptides. We also discuss how unravelling of the 3D structure of CAMs provides novel pharmacological tools for dissection of CAM-induced signalling pathways and offers therapeutic opportunities for a range of neurological disorders....

  15. Xenopus laevis neuronal cell adhesion molecule (nrcam): plasticity of a CAM in the developing nervous system.

    Science.gov (United States)

    Lokapally, Ashwin; Metikala, Sanjeeva; Hollemann, Thomas

    2017-01-01

    Neuron-glial-related cell adhesion molecule (NRCAM) is a neuronal cell adhesion molecule of the L1 immunoglobulin superfamily, which plays diverse roles during nervous system development including axon growth and guidance, synapse formation, and formation of the myelinated nerve. Perturbations in NRCAM function cause a wide variety of disorders, which can affect wiring and targeting of neurons, or cause psychiatric disorders as well as cancers through abnormal modulation of signaling events. In the present study, we characterize the Xenopus laevis homolog of nrcam. Expression of Xenopus nrcam is most abundant along the dorsal midline throughout the developing brain and in the outer nuclear layer of the retina.

  16. Differential mouse-strain specific expression of Junctional Adhesion Molecule (JAM)-B in placental structures.

    Science.gov (United States)

    Stelzer, Ina Annelies; Mori, Mayumi; DeMayo, Francesco; Lydon, John; Arck, Petra Clara; Solano, Maria Emilia

    2016-03-03

    The junctional adhesion molecule (JAM)-B, a member of the immunoglobulin superfamily, is involved in stabilization of interendothelial cell-cell contacts, formation of vascular tubes, homeostasis of stem cell niches and promotion of leukocyte adhesion and transmigration. In the human placenta, JAM-B protein is abundant and mRNA transcripts are enriched in first-trimester extravillous trophoblast in comparison to the villous trophoblast. We here aimed to elucidate the yet unexplored spatio-temporal expression of JAM-B in the mouse placenta. We investigated and semi-quantified JAM-B protein expression by immunohistochemistry in early post-implantation si tes and in mid- to late gestation placentae of various murine mating combinations. Surprisingly, the endothelium of the placental labyrinth was devoid of JAM-B expression. JAM-B was mainly present in spongiotrophoblast cells of the junctional zone, as well as in the fetal vessels of the chorionic plate, the umbilical cord and in maternal myometrial smooth muscle. We observed a strain-specific placental increase of JAM-B protein expression from mid- to late gestation in Balb/c-mated C57BL/6 females, which was absent in DBA/2J-mated Balb/c females. Due to the essential role of progesterone during gestation, we further assessed a possible modulation of JAM-B in mid-gestational placentae deficient in the progesterone receptor (Pgr(-/-)) and observed an increased expression of JAM-B in Pgr(-/-) placentae, compared to Pgr(+/+) tissue samples. We propose that JAM-B is an as yet underappreciated trophoblast lineage-specific protein, which is modulated via the progesterone receptor and shows unique strain-specific kinetics. Future work is needed to elucidate its possible contribution to placental processes necessary to ensuring its integrity, ultimately facilitating placental development and fetal growth.

  17. Relationship between serum adhesion molecules, trace elements and delayed union of tibial and fibula fractures

    Institute of Scientific and Technical Information of China (English)

    Xian-Yu Yan; Zhi-Bang Zhao; Wen-Liang Fan; Qing-Bo Zhu; Ya-Chang Xing

    2017-01-01

    Objective:To investigate the relationship between serum adhesion molecules, trace elements and delayed union of tibial and fibula fractures.Methods:A total of 46 patients with delayed union of tibial and fibula fractures in our hospital from May 2014 to June 2016 were selected as the observation group, 46 patients with normal healing of tibial and fibula fractures were selected as the control group, then the serum adhesion molecules and trace elements levels of two groups at forth, eighth and sixteenth week after the surgery were compared.Results:The serum dhesion molecules levels of observation group at forth, eighth and sixteenth week after the surgery were all higher than those of control group, the serum trace elements levels were all lower than those of control group, and the serum adhesion molecules levels of two groups at eighth week after the surgery were all higher than those at other time, the trace elements levels were all lower than those at other time (allP<0.05).Conclusions:The serum adhesion molecules and trace elements of patients with delayed union of tibial and fibula fractures show obviously abnormal state, so those indexes of those patients should be paid to more monitoring and improvement.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rimpelová, Silvie [Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 5, Prague 6, 166 28 (Czech Republic); Kasálková, Nikola Slepičková; Slepička, Petr [Department of Solid State Engineering, Institute of Chemical Technology, Prague, Technická 5, Prague 6, 166 28 (Czech Republic); Lemerová, Helena [Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 5, Prague 6, 166 28 (Czech Republic); Švorčík, Václav [Department of Solid State Engineering, Institute of Chemical Technology, Prague, Technická 5, Prague 6, 166 28 (Czech Republic); Ruml, Tomáš, E-mail: tomas.ruml@vscht.cz [Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 5, Prague 6, 166 28 (Czech Republic)

    2013-04-01

    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.

  19. Gamma knife irradiation increases cerebral endothelial expression of intercellular adhesion molecule 1 and E-selectin.

    Science.gov (United States)

    Sharp, Christopher D; Jawahar, Ajay; Warren, April C; Elrod, John W; Nanda, Anil; Alexander, J Steven

    2003-07-01

    Alterations in multiple functions of the microvasculature occur in response to gamma irradiation and are thought to contribute to radiation-induced end organ damage by inducing inflammatory responses, particularly leukocyte infiltration into the affected area. Endothelial cell adhesion molecules (ECAMs) mediate leukocyte adhesion and migration. Here, we validate a method to study the effect of Leksell gamma knife stereotactic radiosurgery on the expression of ECAMs on human cerebral endothelium at 0, 24, 48, and 72 hours after irradiation. A human brain endothelial cell line (IHEC) was cultured on 12-mm coverslips and subjected to 50 Gy of collimated gamma irradiation with the Leksell gamma knife (Elekta Instruments, Inc., Atlanta, GA). Lactate dehydrogenase release was measured at 24, 48, and 72 hours after irradiation and caspase-3 at 24, 48, 72, 96, and 120 hours. ECAM expression was measured at postirradiation intervals of 0, 24, 48, and 72 hours by cell enzyme-linked immunoabsorbent assay. We used a cell irradiator composed of two chambers. The upper chamber holds the coverslips firmly in place while they are immersed in media. The lower chamber is connected to a peristaltic pump, which pumps water into the chamber and maintains the media in the upper chamber at 37 degrees C through convection. None of the ECAMs tested was significantly elevated compared with the control basally. Twenty-four hours after irradiation, intercellular adhesion molecule 1 was significantly elevated on brain endothelial cells but there was no significant elevation of E-selectin. Vascular cell adhesion molecule 1 was increased slightly but not significantly and decreased at 48 hours. At 72 hours, E-selectin expression was significantly increased; intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were not altered relative to sham controls. Increased ECAM expression and lactate dehydrogenase release support the idea that the cerebral microvasculature undergoes an

  20. Bio-active molecules modified surfaces enhanced mesenchymal stem cell adhesion and proliferation.

    Science.gov (United States)

    Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

    2017-01-29

    Surface modification of the substrate as a component of in vitro cell culture and tissue engineering, using bio-active molecules including extracellular matrix (ECM) proteins or peptides derived ECM proteins can modulate the surface properties and thereby induce the desired signaling pathways in cells. The aim of this study was to evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs) on glass substrates modified with fibronectin (Fn), collagen (Coll), RGD peptides (RGD) and designed peptide (R-pept) as bio-active molecules. The glass coverslips were coated with fibronectin, collagen, RGD peptide and R-peptide. Bone marrow mesenchymal stem cells were cultured on different substrates and the adhesion behavior in early incubation times was investigated using scanning electron microscopy (SEM) and confocal microscopy. The MTT assay was performed to evaluate the effect of different bio-active molecules on MSCs proliferation rate during 24 and 72 h. Formation of filopodia and focal adhesion (FA) complexes, two steps of cell adhesion process, were observed in MSCs cultured on bio-active molecules modified coverslips, specifically in Fn coated and R-pept coated groups. SEM image showed well adhesion pattern for MSCs cultured on Fn and R-pept after 2 h incubation, while the shape of cells cultured on Coll and RGD substrates indicated that they might experience stress condition in early hours of culture. Investigation of adhesion behavior, as well as proliferation pattern, suggests R-peptide as a promising bio-active molecule to be used for surface modification of substrate in supporting and inducing cell adhesion and proliferation.

  1. Expression of adhesion and activation molecules on lymphocytes during open-heart surgery with cardiopulmonary bypass

    DEFF Research Database (Denmark)

    Toft, P; Tønnesen, Else Kirstine; Zülow, I

    1997-01-01

    Open-heart surgery with cardiopulmonary bypass (CPB) and abdominal surgery are associated with lymphocytopenia. We measured a panel of adhesion and activation molecules on lymphocytes to clarify possible association of CPB with increased expression of these molecules. Eight patients undergoing open......-heart surgery and eight with abdominal surgery were studied. The adhesion molecules CD11a/CD18 (LFA-1_, CD11c/CD18 and CD44 and the activation molecules CD25, CD69, CD71 and MHCII were measured, using monoclonal antibodies and flow cytometry. Lymphocytopenia was observed during CPB and for some hours after both...... open-heart and abdominal surgery. The proportion of CD11a/CD18-positive lymphocytes rose from 67.6 +/- 8% to 86.4 +/- 3% after aortic declamping (p

  2. Matrine inhibits the expression of adhesion molecules in activated vascular smooth muscle cells.

    Science.gov (United States)

    Liu, Jun; Zhang, Lihua; Ren, Yingang; Gao, Yanli; Kang, Li; Lu, Shaoping

    2016-03-01

    Atherosclerosis is a chronic inflammatory disease associated with increased expression of adhesion molecules in vascular smooth muscle cells (VSMCs). Matrine is a main active ingredient of Sophora flavescens roots, which are used to treat inflammatory diseases. However, the effects of matrine on the expression of adhesion molecules in VSMCs have largely remained elusive. Therefore, the present study investigated the effects of matrine on the expression of adhesion molecules in tumor necrosis factor (TNF)‑α‑stimulated human aortic smooth muscle cells (HASMCs). The results showed that matrine inhibited the expression of vascular cell adhesion molecule‑1 (VCAM‑1) and intercellular adhesion molecule‑1 (ICAM‑1) in TNF‑α‑stimulated HASMCs. Matrine markedly inhibited the TNF‑α‑induced expression of nuclear factor (NF)‑κB p65 and prevented the TNF‑α‑caused degradation of inhibitor of NF‑κB; it also inhibited TNF‑α‑induced activation of mitogen‑activated protein kinases (MAPKs). Furthermore, matrine inhibited the production of intracellular reactive oxygen species (ROS) in TNF‑α‑stimulated HASMCs. In conclusion, the results of the present study demonstrated that matrine inhibited the expression of VCAM‑1 and ICAM‑1 in TNF‑α‑stimulated HASMCs via the suppression of ROS production as well as NF‑κB and MAPK pathway activation. Therefore, matrine may have a potential therapeutic use for preventing the advancement of atherosclerotic lesions.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    The neural cell adhesion molecule (NCAM) was recently suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analysis demonstrated the presence of the NCAM in 78% of SCLC patients and in 25% of patients with other cancer forms. NCAM was proposed to be the most sensitive marker...

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

    DEFF Research Database (Denmark)

    Christensen, Claus; Lauridsen, Jes B; Berezin, Vladimir;

    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...

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

    NARCIS (Netherlands)

    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

  6. Cytokines and soluble adhesion molecules in children and adolescents with a tic disorder

    NARCIS (Netherlands)

    Bos-Veneman, Netty G.P.; Bijzet, Johan; Limburg, Pieter C.; Minderaa, Rudolf; Kallenberg, C.; Hoekstra, Pieter J.

    2010-01-01

    Aim: Dysregulation of the immune system may play a role in tic disorders. We screened for immune disturbances by investigating serum levels of cytokines and soluble adhesion molecules in patients with a tic disorder. Methods: Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, soluble IL-2

  7. Cytokine-Induced Cell Surface Expression of Adhesion Molecules in Vascular Endothelial Cells In vitro

    Institute of Scientific and Technical Information of China (English)

    陈红辉; 刘昌勤; 孙圣刚; 梅元武; 童萼塘

    2001-01-01

    Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF-α (1-250 U/ml) or IL-1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF-α (100 U/ml) or IL-1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM-1 and VCAM-1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up-regulated by TNF-α, IL-1β in a concentration- and time-dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM-1 and on VCAM-1 expression. Cytokines might directly induce the expression of ICAM-1 and VCAM-1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.

  8. Adhesion of Model Molecules to Metallic Surfaces, the Implications for Corrosion Protection

    Energy Technology Data Exchange (ETDEWEB)

    De Wit, J. H. W.; Van den Brand, J.; De Wit, F. M.; Mol, J. M. C. [Delf University of Technology and Netherlaands Institute for Metals Research, Delf (Netherlands)

    2008-02-15

    The majority of the described experimental results deal with relatively pure aluminium. Variations were made in the pretreatment of the aluminum substrates and an investigation was performed on the resulting changes in oxide layer composition and chemistry. Subsequently, the bonding behavior of the surfaces was investigated by using model adhesion molecules. These molecules were chosen to represent the bonding functionality of an organic polymer. They were applied onto the pretreated surfaces as a monolayer and the bonding behavior was studied using infrared reflection absorption spectroscopy. A direct and clear relation was found between the hydroxyl fraction on the oxide surfaces and the amount of molecules that subsequently bonded to the surface. Moreover, it was found that most bonds between the oxide surface and organic functional groups are not stable in the presence of water. The best performance was obtained using molecules, which are capable of chemisorption with the oxide surface. Finally, it was found that freshly prepared relatively pure aluminum substrates, which are left in air, rapidly lose their bonding capacity towards organic functional groups. This can be attributed to the adsorption of contamination and water to the oxide surface. in addition the adhesion of a typical epoxy-coated aluminum system was investigated during exposure to water at different temperatures. The coating was found to quite rapidly lose its adhesion upon exposure to water. This rapid loss of adhesion corresponds well with the data where it was demonstrated that the studied epoxy coating only bonds through physisorptive hydrogen bonding, these bonds not being stable in the presence of water. After the initial loss the adhesion of the coating was however found to recover again and even exceeded the adhesion prior to exposure. The improvement could be ascribed to the growth of a thin oxyhydroxide layer on the aluminum substrate, which forms a new, water-stable and stronger bond

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

    LENUS (Irish Health Repository)

    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.

  10. A hot water extract of Curcuma longa inhibits adhesion molecule protein expression and monocyte adhesion to TNF-α-stimulated human endothelial cells.

    Science.gov (United States)

    Kawasaki, Kengo; Muroyama, Koutarou; Yamamoto, Norio; Murosaki, Shinji

    2015-01-01

    The recruitment of arterial leukocytes to endothelial cells is an important step in the progression of various inflammatory diseases. Therefore, its modulation is thought to be a prospective target for the prevention or treatment of such diseases. Adhesion molecules on endothelial cells are induced by proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), and contribute to the recruitment of leukocytes. In the present study, we investigated the effect of hot water extract of Curcuma longa (WEC) on the protein expression of adhesion molecules, monocyte adhesion induced by TNF-α in human umbilical vascular endothelial cells (HUVECs). Treatment of HUVECs with WEC significantly suppressed both TNF-α-induced protein expression of adhesion molecules and monocyte adhesion. WEC also suppressed phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) induced by TNF-α in HUVECs, suggesting that WEC inhibits the NF-κB signaling pathway.

  11. 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

    Directory of Open Access Journals (Sweden)

    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.

  12. Adhesion molecules and chemokines: relation to anthropometric, body composition, biochemical and dietary variables

    Directory of Open Access Journals (Sweden)

    Renata Adrielle Lima Vieira

    2014-08-01

    Full Text Available Introduction: Among the inflammatory mediators involved in the pathogenesis of obesity, the cell adhesion molecules P-selectin, E-selectin, VCAM-1, ICAM-1 and the chemokine MCP-1 stand out. They play a crucial role in adherence of cells to endothelial surfaces, in the integrity of the vascular wall and can be modulated by body composition and dietary pattern. Objectives: To describe and discuss the relation of these cell adhesion molecules and chemokines to anthropometric, body composition, dietary and biochemical markers. Methods: Papers were located using scientific databases by topic searches with no restriction on year of publication. Results: All molecules were associated positively with anthropometric markers, but controversial results were found for ICAM-1 and VCAM-1. Not only obesity, but visceral fat is more strongly correlated with E-selectin and MCP-1 levels. Weight loss influences the reduction in the levels of these molecules, except VCAM-1. The distribution of macronutrients, excessive consumption of saturated and trans fat and a Western dietary pattern are associated with increased levels. The opposite could be observed with supplementation of w-3 fatty acid, healthy dietary pattern, high calcium diet and high dairy intake. Regarding the biochemical parameters, they have inverse relation to HDLC and positive relation to total cholesterol, triglycerides, blood glucose, fasting insulin and insulin resistance. Conclusion: Normal anthropometric indicators, body composition, biochemical parameters and eating pattern positively modulate the subclinical inflammation that results from obesity by reducing the cell adhesion molecules and chemokines.

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

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2011-01-01

    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

  14. Junctional adhesion molecule (JAM)-B supports lymphocyte rolling and adhesion through interaction with alpha4beta1 integrin.

    Science.gov (United States)

    Ludwig, Ralf J; Hardt, Katja; Hatting, Max; Bistrian, Roxana; Diehl, Sandra; Radeke, Heinfried H; Podda, Maurizio; Schön, Michael P; Kaufmann, Roland; Henschler, Reinhard; Pfeilschifter, Josef M; Santoso, Sentot; Boehncke, Wolf-Henning

    2009-10-01

    Junctional adhesion molecule-A (JAM-A), JAM-B and JAM-C have been implicated in leucocyte transmigration. As JAM-B binds to very late activation antigen (VLA)-4, a leucocyte integrin that contributes to rolling and firm adhesion of lymphocytes to endothelial cells through binding to vascular cell adhesion molecule (VCAM)-1, we hypothesized that JAM-B is also involved in leucocyte rolling and firm adhesion. To test this hypothesis, intravital microscopy of murine skin microvasculature was performed. Rolling interactions of murine leucocytes were significantly affected by blockade of JAM-B [which reduced rolling interactions from 9.1 +/- 2.6% to 3.2 +/- 1.2% (mean +/- standard deviation)]. To identify putative ligands, T lymphocytes were perfused over JAM-B-coated slides in a dynamic flow chamber system. JAM-B-dependent rolling and sticking interactions were observed at low shear stress [0.3 dyn/cm(2): 220 +/- 71 (mean +/- standard deviation) versus 165 +/- 88 rolling (P JAM-B- compared with baseline], but not at higher shear forces (1.0 dyn/cm(2)). As demonstrated by antibody blocking experiments, JAM-B-mediated rolling and sticking of T lymphocytes was dependent on alpha4 and beta1 integrin, but not JAM-C expression. To investigate whether JAM-B-mediated leucocyte-endothelium interactions are involved in a disease-relevant in vivo model, adoptive transfer experiments in 2,4,-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reactions were performed in mice in the absence or in the presence of a function-blocking JAM-B antibody. In this model, JAM-B blockade during the sensitization phase impaired the generation of the immune response to DNFB, which was assessed as the increase in ear swelling in untreated, DNFB-challenged mice, by close to 40% [P = 0.037; analysis of variance (anova)]. Overall, JAM-B appears to contribute to leucocyte extravasation by facilitating not only transmigration but also rolling and adhesion.

  15. Cell adhesion molecules regulate contractile ring-independent cytokinesis in Dictyostelium discoideum

    Institute of Scientific and Technical Information of China (English)

    Akira Nagasaki; Masamitsu Kanada; Taro QP Uyeda

    2009-01-01

    To investigate the roles of substrate adhesion in cytokinesis, we established cell lines lacking paxiUin (PAXB) or vinculin (VINA), and those expressing the respective GFP fusion proteins in Dictyostelium discoideum. As in mammalian cells, GFP-PAXB and GFP-VINA formed focal adhesion-like complexes on the cell bottom, paxB cells in suspension grew normally, but on substrates, often failed to divide after regression of the furrow. The efficient cytokinesis of paxB cells in suspension is not because of shear forces to assist abscission, as they divided normally in static suspension culture as well. Double knockout strains lacking mhcA, which codes for myosin I1, and paxB or vinA displayed more severe cytokinetic defects than each single knockout strain. In mitotic wild-type cells, GFP-PAXB was diffusely distributed on the basal membrane, but was strikingly condensed along the polar edges in mitotic mhcA cells. These results are consistent with our idea that Dictyostelium displays two forms of cytokinesis, one that is contractile ringdependent and adhesion-independent, and the other that is contractile ring-independent and adhesion-dependent, and that the latter requires PAXB and VINA. Furthermore, that paxB cells fail to divide normally in the presence of substrate adhesion suggests that this adhesion molecule may play additional signaling roles.

  16. Murine junctional adhesion molecules JAM-B and JAM-C mediate endothelial and stellate cell interactions during hepatic fibrosis.

    Science.gov (United States)

    Hintermann, Edith; Bayer, Monika; Ehser, Janine; Aurrand-Lions, Michel; Pfeilschifter, Josef M; Imhof, Beat A; Christen, Urs

    2016-07-03

    Classical junctional adhesion molecules JAM-A, JAM-B and JAM-C influence vascular permeability, cell polarity as well as leukocyte recruitment and immigration into inflamed tissue. As the vasculature becomes remodelled in chronically injured, fibrotic livers we aimed to determine distribution and role of junctional adhesion molecules during this pathological process. Therefore, livers of naïve or carbon tetrachloride-treated mice were analyzed by immunohistochemistry to localize all 3 classical junctional adhesion molecules. Hepatic stellate cells and endothelial cells were isolated and subjected to immunocytochemistry and flow cytometry to determine localization and functionality of JAM-B and JAM-C. Cells were further used to perform contractility and migration assays and to study endothelial tubulogenesis and pericytic coverage by hepatic stellate cells. We found that in healthy tissue, JAM-A was ubiquitously expressed whereas JAM-B and JAM-C were restricted to the vasculature. During fibrosis, JAM-B and JAM-C levels increased in endothelial cells and JAM-C was de novo generated in myofibroblastic hepatic stellate cells. Soluble JAM-C blocked contractility but increased motility in hepatic stellate cells. Furthermore, soluble JAM-C reduced endothelial tubulogenesis and endothelial cell/stellate cell interaction. Thus, during liver fibrogenesis, JAM-B and JAM-C expression increase on the vascular endothelium. More importantly, JAM-C appears on myofibroblastic hepatic stellate cells linking them as pericytes to JAM-B positive endothelial cells. This JAM-B/JAM-C mediated interaction between endothelial cells and stellate cells stabilizes vessel walls and may control the sinusoidal diameter. Increased hepatic stellate cell contraction mediated by JAM-C/JAM-C interaction may cause intrahepatic vasoconstriction, which is a major complication in liver cirrhosis.

  17. Stability of the Hydrogen and Hydrogen-like Molecules

    OpenAIRE

    Richard, Jean-Marc

    1994-01-01

    We present a simple proof of the stability of the hydrogen molecule $(M^+M^+m^-m^-)$. It does not rely on the proton-to-electron mass ratio $M/m$ being very large, and actually holds for arbitrary values of $M/m$. Some asymmetric molecules of the type $(m_1^+m_2^+m_3^-m_4^-)$ are also stable. Possible applications to molecules containing antiparticles and to exotic hadrons in the quark model are briefly outlined. Revtex Version 3.0, 4 Figures available on request by Fax or Mail.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses.

    Science.gov (United States)

    Dustin, Michael L

    2007-10-01

    The immunological synapse is a stable adhesive junction between a polarized immune effector cell and an antigen-bearing cell. Immunological synapses are often observed to have a striking radial symmetry in the plane of contact with a prominent central cluster of antigen receptors surrounded by concentric rings of adhesion molecules and actin-rich projections. There is a striking similarity between the radial zones of the immunological synapse and the dynamic actinomyosin modules employed by migrating cells. Breaking the symmetry of an immunological synapse generates a moving adhesive junction that can be defined as a kinapse, which facilitates signal integration by immune cells while moving over the surface of antigen-presenting cells.

  20. The Junctional Adhesion Molecule-B regulates JAM-C-dependent melanoma cell metastasis.

    Science.gov (United States)

    Arcangeli, Marie-Laure; Frontera, Vincent; Bardin, Florence; Thomassin, Jeanne; Chetaille, Bruno; Adams, Susanne; Adams, Ralf H; Aurrand-Lions, Michel

    2012-11-16

    Metastasis is a major clinical issue and results in poor prognosis for most cancers. The Junctional Adhesion Molecule-C (JAM-C) expressed by B16 melanoma and endothelial cells has been involved in metastasis of tumor cells through homophilic JAM-C/JAM-C trans-interactions. Here, we show that JAM-B expressed by endothelial cells contributes to murine B16 melanoma cells metastasis through its interaction with JAM-C on tumor cells. We further show that this adhesion molecular pair mediates melanoma cell adhesion to primary Lung Microvascular Endothelial Cells and that it is functional in vivo as demonstrated by the reduced metastasis of B16 cells in Jam-b deficient mice.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    Christensen, Claus; Berezin, Vladimir; Bock, Elisabeth

    2011-10-26

    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-binding immunoglobulin-like modules 2 and 3 of FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c, and FGFR4, and found that all FGFR isoforms, except for FGFR4, interacted with NCAM. The binding affinity of NCAM-FGFR interactions was considerably higher for splice variant 'b' than for splice variant 'c'. We suggest that the expression pattern of various FGFR isoforms determines the cell context-specific effects of NCAM signaling through FGFR.

  3. Regulated intramembrane proteolysis and degradation of murine epithelial cell adhesion molecule mEpCAM.

    Directory of Open Access Journals (Sweden)

    Matthias Hachmeister

    Full Text Available Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein, which is highly and frequently expressed in carcinomas and (cancer-stem cells, and which plays an important role in the regulation of stem cell pluripotency. We show here that murine EpCAM (mEpCAM is subject to regulated intramembrane proteolysis in various cells including embryonic stem cells and teratocarcinomas. As shown with ectopically expressed EpCAM variants, cleavages occur at α-, β-, γ-, and ε-sites to generate soluble ectodomains, soluble Aβ-like-, and intracellular fragments termed mEpEX, mEp-β, and mEpICD, respectively. Proteolytic sites in the extracellular part of mEpCAM were mapped using mass spectrometry and represent cleavages at the α- and β-sites by metalloproteases and the b-secretase BACE1, respectively. Resulting C-terminal fragments (CTF are further processed to soluble Aβ-like fragments mEp-β and cytoplasmic mEpICD variants by the g-secretase complex. Noteworthy, cytoplasmic mEpICD fragments were subject to efficient degradation in a proteasome-dependent manner. In addition the γ-secretase complex dependent cleavage of EpCAM CTF liberates different EpICDs with different stabilities towards proteasomal degradation. Generation of CTF and EpICD fragments and the degradation of hEpICD via the proteasome were similarly demonstrated for the human EpCAM ortholog. Additional EpCAM orthologs have been unequivocally identified in silico in 52 species. Sequence comparisons across species disclosed highest homology of BACE1 cleavage sites and in presenilin-dependent γ-cleavage sites, whereas strongest heterogeneity was observed in metalloprotease cleavage sites. In summary, EpCAM is a highly conserved protein present in fishes, amphibians, reptiles, birds, marsupials, and placental mammals, and is subject to shedding, γ-secretase-dependent regulated intramembrane proteolysis, and proteasome-mediated degradation.

  4. Single molecule force measurements delineate salt, pH and surface effects on biopolymer adhesion

    Science.gov (United States)

    Pirzer, T.; Geisler, M.; Scheibel, T.; Hugel, T.

    2009-06-01

    In this paper we probe the influence of surface properties, pH and salt on the adhesion of recombinant spider silk proteins onto solid substrates with single molecule force spectroscopy. A single engineered spider silk protein (monomeric C16 or dimeric (QAQ)8NR3) is covalently bound with one end to an AFM tip, which assures long-time measurements for hours with one and the same protein. The tip with the protein is brought into contact with various substrates at various buffer conditions and then retracted to desorb the protein. We observe a linear dependence of the adhesion force on the concentration of three selected salts (NaCl, NaH2PO4 and NaI) and a Hofmeister series both for anions and cations. As expected, the more hydrophobic C16 shows a higher adhesion force than (QAQ)8NR3, and the adhesion force rises with the hydrophobicity of the substrate. Unexpected is the magnitude of the dependences—we never observe a change of more than 30%, suggesting a surprisingly well-regulated balance between dispersive forces, water-structure-induced forces as well as co-solute-induced forces in biopolymer adhesion.

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

    DEFF Research Database (Denmark)

    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 surro...... interaction between NCAM and N-cadherin with a number of intracellular partners, as well as on their interaction with the fibroblast growth factor receptor (FGFR)....

  6. Unfavorable cytokine and adhesion molecule profiles during and after pregnancy, in women with gestational diabetes mellitus.

    Science.gov (United States)

    Roca-Rodríguez, María Del Mar; López-Tinoco, Cristina; Fernández-Deudero, Álvaro; Murri, Mora; García-Palacios, María Victoria; García-Valero, María Del Amor; Tinahones, Francisco José; Aguilar-Diosdado, Manuel

    2017-01-01

    Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease. To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery. A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery. In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels. The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Remarkably enhanced adhesion of coherently aligned catechol-terminated molecules on ultraclean ultraflat gold nanoplates

    Science.gov (United States)

    Lee, Miyeon; Park, Changjun; Lee, Hyoban; Kim, Hongki; Kim, Sang Youl; In, Insik; Kim, Bongsoo

    2016-11-01

    We report the characterization and formation of catechol-terminated molecules immobilized on gold nanoplates (Au NPLs) using N-(3,4-dihydroxyphenethyl)-2-mercaptoacetamide (Cat-EAA-SH). Single-crystalline Au NPLs, synthesized using a one-step chemical vapor transport method, have ultraclean and ultraflat surfaces that make Cat-EAA-SH molecules aligned into a well-ordered network of a large-scale. Topographic study of the catechol-terminated molecules on Au NPLs using atomic force microscopy showed more orderly orientation and higher density, leading to significantly higher adhesion as observed from local force-distance curves than those on other Au surfaces. These coherently aligned catechol-terminated molecules on the atomically smooth gold surface led to significanty more reproducible and thus more physico-chemically meaningful measurements than was possible before by employing rough gold surfaces.

  9. Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients

    Science.gov (United States)

    Vargas-Robles, Hilda; Serrano, Alberto Maceda; Lozano-Nuevo, Jose Juan; Escalante-Acosta, Bruno Alfonso

    2009-01-01

    Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in normotensive type-2 diabetic patients. Results: We found significant correlations between ICAM-1 (r = 0.69, p < 0.001 95% IC 0.65 to 0.82) and VCAM-1 (r = 0.4, p < 0.03, 95% IC 0.65 to 0.82) levels and maximal carotid artery intimal-medial thickness, whereas no correlation was observed with E-selectin. Methods: We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. Conclusion: Our results suggest that ICAM-1 and VCAM-1 are markers associated, and correlated with the degree of atherosclerosis in normotensive type-2 diabetic patients. PMID:19717975

  10. Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia.

    Science.gov (United States)

    Chakrabarti, D; Huang, X; Beck, J; Henrich, J; McFarland, N; James, R F; Stewart, T A

    1996-10-01

    The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Stabilization of protein-protein interactions by small molecules.

    Science.gov (United States)

    Giordanetto, Fabrizio; Schäfer, Anja; Ottmann, Christian

    2014-11-01

    Protein-protein interactions (PPIs) are implicated in every disease and mastering the ability to influence PPIs with small molecules would considerably enlarge the druggable genome. Whereas inhibition of PPIs has repeatedly been shown to work successfully, targeted stabilization of PPIs is underrepresented in the literature. This is all the more surprising because natural products like FK506, rapamycin, brefeldin, forskolin and fusicoccin confer their physiological activity by stabilizing specific PPIs. However, recently a number of very interesting synthetic molecules have been reported from drug discovery projects that indeed achieve their desired activities by stabilizing either homo- or hetero-oligomeric complexes of their target proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Skov, Vibe; Larsen, Thomas Stauffer;

    2011-01-01

    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 important...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Topographical control of multiple cell adhesion molecules for traction force microscopy.

    Science.gov (United States)

    Polio, Samuel R; Parameswaran, Harikrishnan; Canović, Elizabeth P; Gaut, Carolynn M; Aksyonova, Diana; Stamenović, Dimitrije; Smith, Michael L

    2014-03-01

    Cellular traction forces are important quantitative measures in cell biology as they have provided much insight into cell behavior in contexts such as cellular migration, differentiation, and disease progression. However, the complex environment in vivo permits application of cell traction forces through multiple types of cell adhesion molecules. Currently available approaches to differentiate traction forces among multiple cell adhesion molecules are limited to specialized approaches to decouple cell-cell from cell-extracellular matrix (ECM) tractions. Here, we present a technique which uses indirect micropatterning onto a polyacrylamide gel to pattern multiple, spatially distinct fluorescently labeled ECM proteins, specifically gelatin and fibronectin (Fn), and confine the area to which cells can adhere. We found that cells interacting with both gelatin and Fn altered their traction forces significantly in comparison to cells on Fn-only substrates. This crosstalk interaction resulted in a decrease in overall traction forces on dual-patterned substrates as compared to cells on Fn-only substrates. This illustrates the unique need to study such interactions and demonstrates great potential in future studies in multi-ligand environments. Current micropatterning techniques on glass can easily be adapted to present other protein classes, such as cadherins, while maintaining control of adhesion spacing, cell spread area, and stiffness, each of which are important regulators of cell mechanobiology.

  20. Adhesion of single polyelectrolyte molecules on silica, mica, and bitumen surfaces.

    Science.gov (United States)

    Long, Jun; Xu, Zhenghe; Masliyah, Jacob H

    2006-02-14

    In a recent study (Energy Fuels 2005, 19, 936), a partially hydrolyzed polyacrylamide (HPAM) was used as a process aid to recover bitumen from oil sand ores. It was found that HPAM addition at the bitumen extraction step not only improved bitumen recovery but also enhanced fine solids settling in the tailings stream. To understand the role of HPAM, single-molecule force spectroscopy was employed for the first time to measure the desorption/adhesion forces of single HPAM molecules on silica, mica, and bitumen surfaces using an atomic force microscope (AFM). Silicon wafers with an oxidized surface layer and newly cleaved mica were used, respectively, to represent sand grains and clays in oil sands. The force measurements were carried out in deionized water and in commercial plant process water under equilibrium conditions. The desorption/adhesion forces of HPAM obtained on mica, silica, and bitumen surfaces were approximately 200, 40, and 80 pN in deionized water and approximately 100, 50, and 40 pN in the plant process water, respectively. The measured adhesion forces together with the zeta potential values of these surfaces indicate that the polymer would preferentially adsorb onto clay surfaces rather than onto bitumen surfaces. It is the selective adsorption of HPAM that benefits both bitumen recovery and tailings settling when the polymer was added directly to the bitumen extraction process at an appropriate dosage.

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

    NARCIS (Netherlands)

    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

  2. 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

    DEFF Research Database (Denmark)

    Køhler, Lene B; Christensen, Claus; Rossetti, Clara

    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...... 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...

  3. Tetraspanins CD81 and CD82 facilitate α4β1-mediated adhesion of human erythroblasts to vascular cell adhesion molecule-1.

    Directory of Open Access Journals (Sweden)

    Frances A Spring

    Full Text Available The proliferation and terminal differentiation of erythroid progenitors occurs in human bone marrow within erythroblastic islands, specialised structures consisting of a central macrophage surrounded by developing erythroid cells. Many cell-cell and cell-matrix adhesive interactions maintain and regulate the co-ordinated daily production of reticulocytes. Erythroid cells express only one integrin, α4β1, throughout differentiation, and its interactions with both macrophage Vascular Cell Adhesion Molecule-1 and with extracellular matrix fibronectin are critical for erythropoiesis. We observed that proerythroblasts expressed a broad tetraspanin phenotype, and investigated whether any tetraspanin could modulate integrin function. A specific association between α4β1 and CD81, CD82 and CD151 was demonstrated by confocal microscopy and co-immune precipitation. We observed that antibodies to CD81 and CD82 augmented adhesion of proerythroblasts to Vascular Cell Adhesion Molecule-1 but not to the fibronectin spliceoforms FnIII12-IIICS-15 and FnIII12-15. In contrast, different anti-CD151 antibodies augmented or inhibited adhesion of proerythroblasts to Vascular Cell Adhesion Molecule-1 and the fibronectin spliceoform FnIII12-IIICS-15 but not to FnIII12-15. These results strongly suggest that tetraspanins have a functional role in terminal erythropoiesis by modulating interactions of erythroblast α4β1 with both macrophages and extracellular matrix.

  4. Bonding stability of adhesive systems to eroded dentin.

    Science.gov (United States)

    Cruz, Janaina Barros; Bonini, Gabriela; Lenzi, Tathiane Larissa; Imparato, José Carlos Pettorossi; Raggio, Daniela Prócida

    2015-01-01

    This in vitro study evaluated the immediate and 6 months microshear bond strength (µSBS) of different adhesive systems to sound and eroded dentin. Sixty bovine incisors were embedded in acrylic resin and ground to obtain flat buccal dentin surfaces. Specimens were randomly allocated into two groups: sound dentin (immersion in artificial saliva) and eroded dentin (erosive challenge following a pH cycling model comprising 4 ×/day Sprite Light® drink for 10 days). Then, specimens were reassigned according to the adhesive system: etch-and-rinse adhesive (Adper Single Bond), two-step self-etch system (Clearfil SE Bond), or one-step self-etch adhesive (Adper Easy One). Polyethylene tubes with an internal diameter of 0.76 mm were placed over pre-treated dentin and filled with resin composite (Z250). Half of the specimens were evaluated by the µSBS test after 24 h, and the other half 6 months later, after water storage at 37 °C. Failure mode was evaluated using a stereomicroscope (400 ×). Data were analyzed by three-way repeated measures analysis of variance and Tukey's post hoc tests (α = 0.05). After 6 months of water aging, marked reductions in µSBS values were observed, irrespective of the substrate. The µSBS values for eroded dentin were lower than those obtained for sound dentin. No difference in bonding effectiveness was observed among adhesive systems. For all groups, adhesive/mixed failure was observed. In conclusion, eroded dentin compromises the bonding quality of adhesive systems over time.

  5. Bonding stability of adhesive systems to eroded dentin

    Directory of Open Access Journals (Sweden)

    Janaina Barros CRUZ

    2015-01-01

    Full Text Available This in vitro study evaluated the immediate and 6 months microshear bond strength (µSBS of different adhesive systems to sound and eroded dentin. Sixty bovine incisors were embedded in acrylic resin and ground to obtain flat buccal dentin surfaces. Specimens were randomly allocated into two groups: sound dentin (immersion in artificial saliva and eroded dentin (erosive challenge following a pH cycling model comprising 4 ×/day Sprite Light® drink for 10 days. Then, specimens were reassigned according to the adhesive system: etch-and-rinse adhesive (Adper Single Bond, two-step self-etch system (Clearfil SE Bond, or one-step self-etch adhesive (Adper Easy One. Polyethylene tubes with an internal diameter of 0.76 mm were placed over pre-treated dentin and filled with resin composite (Z250. Half of the specimens were evaluated by the µSBS test after 24 h, and the other half 6 months later, after water storage at 37°C. Failure mode was evaluated using a stereomicroscope (400×. Data were analyzed by three-way repeated measures analysis of variance and Tukey’s post hoc tests (α = 0.05. After 6 months of water aging, marked reductions in µSBS values were observed, irrespective of the substrate. The µSBS values for eroded dentin were lower than those obtained for sound dentin. No difference in bonding effectiveness was observed among adhesive systems. For all groups, adhesive/mixed failure was observed. In conclusion, eroded dentin compromises the bonding quality of adhesive systems over time.

  6. N-Cadherin, a cell adhesion molecule involved in establishment of embryonic left-right asymmetry.

    Science.gov (United States)

    García-Castro, M I; Vielmetter, E; Bronner-Fraser, M

    2000-05-12

    Within the bilaterally symmetric vertebrate body plan, many organs develop asymmetrically. Here, it is demonstrated that a cell adhesion molecule, N-cadherin, is one of the earliest proteins to be asymmetrically expressed in the chicken embryo and that its activity is required during gastrulation for proper establishment of the left-right axis. Blocking N-cadherin function randomizes heart looping and alters the expression of Snail and Pitx2, later components of the molecular cascade that regulate left-right asymmetry. However, the expression of other components of this cascade (Nodal and Lefty) was unchanged after blocking N-cadherin function, suggesting the existence of parallel pathways in the establishment of left-right morphogenesis. Here, the results suggest that N-cadherin-mediated cell adhesion events are required for establishment of left-right asymmetry.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    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 neurite outgrowth subsequently was analyzed. P2, but not P1-B, induced neurite outgrowth in the absence of NCAM binding in trans. When PC12-E2 cells were grown on monolayers of NCAM-expressing fibroblasts, the effect of both P1-B and P2 on neurite outgrowth was dependent on peptide concentrations. P1-B...

  8. Junctional adhesion molecule-C promotes metastatic potential of HT1080 human fibrosarcoma.

    Science.gov (United States)

    Fuse, Chiaki; Ishida, Yuuki; Hikita, Tomoya; Asai, Tomohiro; Oku, Naoto

    2007-03-16

    The junctional adhesion molecule (JAM) family is a key molecule in a process called transendothelial migration or diapedesis. Here, we report implications of JAM-C in cancer metastasis. We first determined the mRNA expression of JAMs in 19 kinds of cancer cell lines. JAM-C was expressed in most of tumors having potent metastatic properties. Especially in murine K-1735 melanoma cell lines, the highly metastatic sublines (M2 and X21) strongly expressed JAM-C when compared with the poorly metastatic ones (C-10 and C23). Next, we investigated the role of JAM-C in cancer metastasis by using human JAM-C (hJAM-C) gene-transfected HT1080 fibrosarcoma cells. In comparison with mock-transfected HT1080 cells, these cells showed a significant increase in the adhesion to various extracellular substrates and the invasion across a Matrigel-coated membrane. The knockdown of hJAM-C using small interfering RNA resulted in the suppression of both the adhesion and the invasion of HT1080 cells, suggesting that endogenous hJAM-C might be involved in tumor metastasis. Finally, we studied the role of hJAM-C in an in vivo experimental metastatic model. The results showed that the overexpression of hJAM-C in HT1080 cells significantly decreased the life spans of the tumorbearing mice. In contrast, the knockdown of hJAM-C in HT1080 cells suppressed the weight gain of the lungs with metastatic colonies. We conclude that the expression of JAM-C promotes metastasis by enhancing both the adhesion of cancer cells to extracellular matrices and the subsequent invasion.

  9. Receptor-like Molecules on Human Intestinal Epithelial Cells Interact with an Adhesion Factor from Lactobacillus reuteri

    OpenAIRE

    Matsuo, Yosuke; MIYOSHI, Yukihiro; Okada, Sanae; SATOH, Eiichi

    2012-01-01

    A surface protein of Lactobacillus reuteri, mucus adhesion-promoting protein (MapA), is considered to be an adhesion factor. MapA is expressed in L. reuteri strains and adheres to piglet gastric mucus, collagen type I, and human intestinal epithelial cells such as Caco-2. The aim of this study was to identify molecules that mediate the attachment of MapA from L. reuteri to the intestinal epithelial cell surface by investigating the adhesion of MapA to receptor-like molecules on Caco-2 cells. ...

  10. Soluble endothelial adhesion molecules and inflammation markers in patients with beta-thalassemia intermedia.

    Science.gov (United States)

    Kanavaki, Ino; Makrythanasis, Periklis; Lazaropoulou, Christina; Tsironi, Maria; Kattamis, Antonis; Rombos, Ioannis; Papassotiriou, Ioannis

    2009-01-01

    The term thalassemia intermedia, indicates a clinical condition of intermediate severity between thalassaemia minor, the asymptomatic carrier, and thalassaemia major, the transfusion-dependent, severe form. Thromboembolic events frequently complicate the outcome of thalassemia intermedia patients, reflecting a hypercoagulable state to which endothelial activation is believed to play an important role. The aim of this study was to evaluate the levels of soluble endothelial adhesion molecules that reflect endothelial activation and dysfunction and levels of chronic inflammation markers in the serum of beta-thalassemia intermedia patients. Thirty-five Greek patients with beta-thalassemia intermedia that have received different types of treatment (Hydroxyurea, splenectomy, untreated), aged 8-63 years, were included in the study. Twenty apparently healthy individuals matched for age and sex, formed the control group. Measurements of sVCAM-1, sICAM-1, sTM, P-selectin, E-selectin and CRP levels were performed using immunoassays. We found that all endothelial adhesion molecules and CRP were significantly increased in patients (ptreatment. A negative correlation was observed between levels of sICAM-1 and sTM and this finding agrees with the results of studies, which propose this correlation as a predictive marker of increased risk for vascular damage. No correlation was observed between endothelial adhesion molecules and inflammation markers. These findings support the hypothesis that a serious degree of endothelial activation and damage along with a state of chronic inflammation underlie the pathophysiology of beta-thalassemia intermedia. Furthermore, these findings are of particular importance in patients who can otherwise be characterized by a subtle clinical phenotype and may have an important role in their clinical care.

  11. Altered expression of adhesion molecules on peripheral blood leukocytes in feline infectious peritonitis.

    Science.gov (United States)

    Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Desmarets, Lowiese M B; Vermeulen, Ben L; Dewerchin, Hannah L; Nauwynck, Hans J

    2013-10-25

    Feline infectious peritonitis (FIP) is a fatal, coronavirus-induced systemic disease in domestic and wild felids. The pathology associated with FIP (multifocal granulomatous vasculitis) is considered to be elicited by exaggerated activation and subsequent extravasation of leukocytes. As changes in the expression of adhesion molecules on circulating leukocytes precede their margination and emigration, we reasoned that the expression of leukocyte adhesion molecules may be altered in FIP. In present study, the expression of principal adhesion molecules involved in leukocyte transmigration (CD15s, CD11a, CD11b, CD18, CD49d, and CD54) on peripheral blood leukocytes from cats with naturally occurring FIP (n=15) and controls (n=12) was quantified by flow cytometry using a formaldehyde-based rapid leukocyte preparation technique. T- and B-lymphocytes from FIP patients exhibit higher expression of both subunits (CD11a and CD18) composing the β2 integrin lymphocyte function-associated antigen (LFA)-1. In addition, the expression of the α4 subunit (CD49d) of the β1 integrin very late antigen (VLA)-4 was elevated on B-lymphocytes from FIP patients. The expression of CD11b and CD18, that combine to form the β2 integrin macrophage-1 antigen (Mac-1), was elevated on monocytes, whereas the density of CD49d was reduced on this population in FIP. Granulocytes of FIP cats displayed an increased expression of the α chain of Mac-1 (CD11b). These observations suggest that leukocytes from FIP patients show signs of systemic activation causing them to extravasate into surrounding tissues and ultimately contribute to pyogranuloma formation seen in FIP.

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

    DEFF Research Database (Denmark)

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

    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....... The first pathway was associated with activation of FGFR, phospholipase Cgamma, and production of diacylglycerol, and the second pathway involved Src-family kinases. Moreover, NCAM-mediated Ca2+ entry required activation of nonselective cation and T-type voltage-gated Ca2+ channels. These channels, together...

  13. Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression.

    Science.gov (United States)

    Wagener, F A; da Silva, J L; Farley, T; de Witte, T; Kappas, A; Abraham, N G

    1999-10-01

    Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme; the latter generates pro-oxidant products, including free radicals. Two HO isozymes, the products of distinct genes, have been described; HO-1 is the inducible isoform, whereas HO-2 is suggested to be constitutively expressed. We studied the inducing effect of several metal compounds (CoCl(2), stannic mesoporphyrin, and heme) on HO activity. Additionally, we studied HO-1 expression in experimental models of adhesion molecule expression produced by heme in endothelial cells, and the relationship of HO-1 expression to the induced adhesion molecules. Flow cytometry analysis showed that heme induces intracellular adhesion molecule 1 (ICAM-1) expression in a concentration (10-100 microM)- and time (1-24 h)-dependent fashion in human umbilical vein endothelial cells. Pretreatment with stannic mesoporphyrin, an inhibitor of HO activity, caused a 2-fold increase in heme-induced ICAM-1 expression. In contrast, HO induction by CoCl(2) decreased heme-induced ICAM-1 expression by 33%. To examine the contribution of HO-1 and HO-2 to endothelial HO activity, specific antisense oligonucleotides (ODNs) of each isoform were tested for their specificity to inhibit HO activity in cells exposed to heme. Endothelial cells exposed to heme elicited increased HO activity, which was prevented (70%) by HO-1 antisense ODNs. HO-2 antisense ODN inhibited heme-induced HO activity by 21%. Addition of HO-1 antisense ODNs prevented heme degradation and resulted in elevation of microsomal heme. Western blot analysis showed that HO-1 antisense ODNs selectively inhibited HO-1 protein and failed to inhibit HO-2 protein. Incubation of endothelial cells with HO-1 antisense enhanced heme-dependent increase of ICAM-1. In contrast, addition of HO-2 antisense to endothelial cells failed to increase adhesion molecules. The role of glutathione, an important antioxidant, was examined on heme

  14. The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

    Energy Technology Data Exchange (ETDEWEB)

    Fransen, E.; Vits, L.; Van Camp, G.; Willems, P.J. [Univ. of Antwerp (Belgium)

    1996-07-12

    Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. 22 refs., 3 figs., 4 tabs.

  15. Structural model and trans-interaction of the entire ectodomain of the olfactory cell adhesion molecule

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Kristensen, Ole; Rasmussen, Kim K;

    2011-01-01

    The ectodomain of olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM) consists of five immunoglobulin (Ig) domains (IgI-V), followed by two fibronectin-type 3 (Fn3) domains (Fn3I-II). A complete structural model of the entire ectodomain of human OCAM has been assembled from crystal structures...... of six recombinant proteins corresponding to different regions of the ectodomain. The model is the longest experimentally based composite structural model of an entire IgCAM ectodomain. It displays an essentially linear arrangement of IgI-V, followed by bends between IgV and Fn3I and between Fn3I and Fn3...

  16. Titanium dioxide nanoparticles induce the expression of early and late receptors for adhesion molecules on monocytes

    OpenAIRE

    Rueda-Romero, Cristhiam; Hernández-Pérez, Guillermina; Ramos-Godínez, Pilar; Vázquez-López, Inés; Raúl Omar QUINTANA-BELMARES; Huerta-García, Elizabeth; Stepien, Ewa; López-Marure, Rebeca; Montiel-Dávalos, Angélica; Alfaro-Moreno, Ernesto

    2016-01-01

    Background There is growing evidence that exposure to titanium dioxide nanoparticles (TiO2 NPs) could be harmful. Previously, we have shown that TiO2 NPs induces endothelial cell dysfunction and damage in glial cells. Considering that inhaled particles can induce systemic effects and the evidence that nanoparticles may translocate out of the lungs, we evaluated whether different types of TiO2 NPs can induce the expression of receptors for adhesion molecules on monocytes (U937 cell line). We e...

  17. Stability conditions of diatomic molecules in Heisenbergs picture: inspired from the stability theory of lasers

    CERN Document Server

    Jahanpanah, Jafar

    2015-01-01

    The vibrational motion equations of both homo and hetero-nuclei diatomic molecules are here derived for the first time. A diatomic molecule is first considered as a one dimensional quantum mechanics oscillator. The second and third-order Hamiltonian operators are then formed by substituting the number operator for the quantum number in the corresponding vibrational energy eigenvalues. The expectation values of relative position and linear momentum operators of two oscillating atoms are calculated by solving Heisenbergs equations of motion. Subsequently, the expectation values of potential and kinetics energy operators are evaluated in all different vibrational levels of Morse potential. On the other hand, the stability theory of optical oscillators (lasers) is exploited to determine the stability conditions of an oscillating diatomic molecule.It is peculiarly turned out that the diatomic molecules are exactly dissociated at the energy level in which their equations of motion become unstable. We also determine...

  18. Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1.

    Directory of Open Access Journals (Sweden)

    Devon M Fitzgerald

    Full Text Available The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs, and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7 rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10(-12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression.

  19. Circulating Adhesion Molecules in Patients with Keshan Disease and Their Relationship with Coxsackie B Virus Infection

    Institute of Scientific and Technical Information of China (English)

    Congsheng LI; Xiaolin NIU; Cong LEI

    2009-01-01

    This study determined the levels of serum soluble intercellular adhesion molecule-1 (sI-CAM-1) and soluble vascular cell adhesion molecular-1 (sVCAM-1) in patients with different types of Keshan disease (KD),examined the relationship between Coxsackie B virus-specific lgM antibody (CBV-IgM) and sICAM-1 or sVCAM-1 in KD patients,and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications.The levels of serum slCAM-1,sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease (CKD),27 with latent Keshan disease (LKD) and 28 healthy controis.The subjects in different groups were adjusted for sex and age.Echocardiography was adopted to determine left ventrieular ejection fraction (LVEF) in 22 patients with CKD.The results showed that CKD patients had significantly higher levels of sICAM-1 and sVCAM-1 than LKD patients and healthy controls (P<0.01 for all).And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls (P<0.05).A negative correlation was found between LVEF and sICAM-1 or sVCAM-1 in CKD patients.The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls.In CVB-specific IgM positive patients,the levels of serum sICAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart.It was concluded that the increase in the levels of sICAM-1 and sVCAM-1 suggests the progression of inflammation in KD.sICAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function.The increased serum sICAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

  20. Decreased pulmonary inflammation after ethanol exposure and burn injury in intercellular adhesion molecule-1 knockout mice.

    Science.gov (United States)

    Bird, Melanie D; Morgan, Michelle O; Ramirez, Luis; Yong, Sherri; Kovacs, Elizabeth J

    2010-01-01

    Clinical and laboratory evidence suggests that alcohol consumption dysregulates immune function. Burn patients who consume alcohol before their injuries demonstrate higher rates of morbidity and mortality, including acute respiratory distress syndrome, than patients without alcohol at the time of injury. Our laboratory observed higher levels of proinflammatory cytokines and leukocyte infiltration in the lungs of mice after ethanol exposure and burn injury than with either insult alone. To understand the mechanism of the increased pulmonary inflammatory response in mice treated with ethanol and burn injury, we investigated the role of intercellular adhesion molecule (ICAM)-1. Wild-type and ICAM-1 knockout (KO) mice were treated with vehicle or ethanol and subsequently given a sham or burn injury. Twenty-four hours postinjury, lungs were harvested and analyzed for indices of inflammation. Higher numbers of neutrophils were observed in the lungs of wild-type mice after burn and burn with ethanol treatment. This increase in pulmonary inflammatory cell accumulation was significantly lower in the KO mice. In addition, levels of KC, interleukin-1beta, and interleukin-6 in the lung were decreased in the ICAM-1 KO mice after ethanol exposure and burn injury. Interestingly, no differences were observed in serum or lung tissue content of soluble ICAM-1 24 hours postinjury. These data suggest that upregulation of adhesion molecules such as ICAM-1 on the vascular endothelium may play a critical role in the excessive inflammation seen after ethanol exposure and burn injury.

  1. Resveratrol abrogates adhesion molecules and protects against TNBS-induced ulcerative colitis in rats.

    Science.gov (United States)

    Abdallah, Dalaal M; Ismael, Naglaa R

    2011-11-01

    Resveratrol, a polyphenol compound with anti-inflammatory properties, has been previously evaluated for its beneficial effects in several ulcerative colitis models. However, the current study elucidates the effect of resveratrol on adhesion molecules, as well as its antioxidant efficacy in a trinitrobenzene sulfonic acid (TNBS)-induced ulcerative-colitis model. Colitis was induced by rectal instillation of TNBS, followed by daily per os administration of either sulphasalazine (300 mg/kg) or resveratrol (2 and 10 mg/kg) for 7 days. Administration of resveratrol decreased the ulcerative area and colon mass index; these effects were further supported by the reduction in colon inflammation grades, as well as histolopathological changes, and reflected by the stalling of body mass loss. The anti-inflammatory effects of resveratrol were indicated by lowered myeloperoxidase activity, and by suppressing ICAM-1 and VCAM-1 levels in the colon and serum. In addition, it restored a reduced colonic nitric oxide level and reinstated its redox balance, as evidenced by the suppression of lipid peroxides and prevention of glutathione depletion. The anti-ulcerative effect of the higher dose of resveratrol was comparable with those of sulphasalazine. The study confirms the anti-ulcerative effect of resveratrol in TNBS-induced experimental colitis via reduction of neutrophil infiltration, inhibition of adhesive molecules, and restoration of the nitric oxide level, as well as the redox status.

  2. Intercellular adhesion molecule-1 blockade attenuates inflammatory response and improves microvascular perfusion in rat pancreas grafts.

    Science.gov (United States)

    Preissler, Gerhard; Eichhorn, Martin; Waldner, Helmut; Winter, Hauke; Kleespies, Axel; Massberg, Steffen

    2012-10-01

    After pancreas transplantation (PTx), early capillary malperfusion and leukocyte recruitment indicate the manifestation of severe ischemia/reperfusion injury (IRI). Oscillatory blood-flow redistribution (intermittent capillary perfusion, IP), leading to an overall decrease in erythrocyte flux, precedes complete microvascular perfusion failure with persistent blood flow cessation. We addressed the role of intercellular adhesion molecule-1 (ICAM-1) for leukocyte-endothelial interactions (LEIs) after PTx and evaluated the contribution of IP and malperfusion. Pancreas transplantation was performed in rats after 18-hour preservation, receiving either isotype-matched IgG or monoclonal anti-ICAM-1 antibodies (10 mg/kg intravenously) once before reperfusion. Leukocyte-endothelial interaction, IP, erythrocyte flux, and functional capillary density, respectively, were examined in vivo during 2-hour reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry. In grafts of IgG-treated animals, IP was encountered already at an early stage after reperfusion and steadily increased over 2 hours, whereas erythrocyte flux declined continuously. In contrast, inhibition of ICAM-1 significantly improved erythrocyte flux and delayed IP appearance by 2 hours. Further, anti-ICAM-1 significantly reduced LEI and leukocyte tissue infiltration when compared to IgG; edema development was less pronounced in response to anti-ICAM-1 monoclonal antibody. Intercellular adhesion molecule-1 blockade significantly attenuates IRI via immediate reduction of LEI and concomitant improvement of capillary perfusion patterns, emphasizing its central role during IRI in PTx.

  3. MCAM: a database to accelerate the identification of functional cell adhesion molecules.

    Science.gov (United States)

    Sadanandam, Anguraj; Pal, Sudipendra Nath; Ziskovsky, Joe; Hegde, Prathibha; Singh, Rakesh K

    2008-01-01

    In the post-genomic era, computational identification of cell adhesion molecules (CAMs) becomes important in defining new targets for diagnosis and treatment of various diseases including cancer. Lack of a comprehensive CAM-specific database restricts our ability to identify and characterize novel CAMs. Therefore, we developed a comprehensive mammalian cell adhesion molecule (MCAM) database. The current version is an interactive Web-based database, which provides the resources needed to search mouse, human and rat-specific CAMs and their sequence information and characteristics such as gene functions and virtual gene expression patterns in normal and tumor tissues as well as cell lines. Moreover, the MCAM database can be used for various bioinformatics and biological analyses including identifying CAMs involved in cell-cell interactions and homing of lymphocytes, hematopoietic stem cells and malignant cells to specific organs using data from high-throughput experiments. Furthermore, the database can also be used for training and testing existing transmembrane (TM) topology prediction methods specifically for CAM sequences. The database is freely available online at http://app1.unmc.edu/mcam.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Fibroblast growth factor-regulated palmitoylation of the neural cell adhesion molecule determines neuronal morphogenesis.

    Science.gov (United States)

    Ponimaskin, Evgeni; Dityateva, Galina; Ruonala, Mika O; Fukata, Masaki; Fukata, Yuko; Kobe, Fritz; Wouters, Fred S; Delling, Markus; Bredt, David S; Schachner, Melitta; Dityatev, Alexander

    2008-09-03

    During development of the nervous system, short- and long-range signals cooperate to promote axonal growth, guidance, and target innervation. Particularly, a short-range signal transducer, the neural cell adhesion molecule (NCAM), stimulates neurite outgrowth via mechanisms that require posttranslational modification of NCAM and signaling via receptors to a long-range messenger, the fibroblast growth factor (FGF). In the present study we further characterized a mechanism which regulates the functional interplay between NCAM and FGF receptor(s). We show that activation of FGF receptor(s) by FGF2 leads to palmitoylation of the two major transmembrane NCAM isoforms, NCAM140 and NCAM180, translocation of NCAM to GM1 ganglioside-containing lipid rafts, and stimulation of neurite outgrowth of hippocampal neurons. Ablation of NCAM, mutation of NCAM140 or NCAM180 palmitoylation sites, or pharmacological suppression of NCAM signaling inhibited FGF2-stimulated neurite outgrowth. Of the 23 members of the aspartate-histidine-histidine-cysteine (DHHC) domain containing proteins, DHHC-7 most strongly stimulated palmitoylation of NCAM, and enzyme activity was enhanced by FGF2. Thus, our study uncovers a molecular mechanism by which a growth factor regulates neuronal morphogenesis via activation of palmitoylation, which in turn modifies subcellular location and thus signaling via an adhesion molecule.

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

    Science.gov (United States)

    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.

  7. MCAM: A Database to Accelerate the Identification of Functional Cell Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    Rakesh K. Singh

    2008-01-01

    Full Text Available In the post-genomic era, computational identification of cell adhesion molecules (CAMs becomes important in defining new targets for diagnosis and treatment of various diseases including cancer. Lack of a comprehensive CAM-specific database restricts our ability to identify and characterize novel CAMs. Therefore, we developed a comprehensive mammalian cell adhesion molecule (MCAM database. The current version is an interactive Web-based database, which provides the resources needed to search mouse, human and rat-specific CAMs and their sequence information and characteristics such as gene functions and virtual gene expression patterns in normal and tumor tissues as well as cell lines. Moreover, the MCAM database can be used for various bioinformatics and biological analyses including identifying CAMs involved in cell-cell interactions and homing of lymphocytes, hematopoietic stem cells and malignant cells to specific organs using data from high-throughput experiments. Furthermore, the database can also be used for training and testing existing transmembrane (TM topology prediction methods specifically for CAM sequences. The database is freely available online at http://app1.unmc.edu/mcam.

  8. Differential effects of EGF and amphiregulin on adhesion molecule expression and migration of colon carcinoma cells.

    Science.gov (United States)

    Solic, N; Davies, D E

    1997-08-01

    Epidermal growth factor (EGF) is a potent morphogen affecting cell shape and motility through regulation of adhesive interactions. We have characterized the morphological effects of EGF on GP2d and GP5d colon carcinoma cell lines and have compared the ability of the heparin-binding EGF receptor ligand amphiregulin (AR) to elicit the same effects. EGF induced a marked epithelial-mesenchymal transition in both cell lines. This effect was evident at 7 pM EGF and was associated with a reduction in cellular adherens junctions and diminished cell-cell contact; it was also associated with an increase in expression of alpha2-integrin as well as enhanced adhesion to the substratum and cell spreading. These changes in adhesion molecule expression were accompanied by enhanced migration on collagen. Blockade of cell growth with mitomycin C did not prevent the EGF-induced morphological change, showing that the mitogenic and morphogenic responses of the GP cells were separable. The phosphatidyl inositol (PI) 3-kinase inhibitor wortmannin inhibited basal proliferation but had no effect on the EGF-induced morphological change, further suggesting that the PI 3-kinase pathway was not involved in the morphogenic response of these cells. Amphiregulin stimulated proliferation of both cell lines, but could only elicit a modest morphological change if used at considerably higher doses or if growth was blocked with mitomycin C. In cells treated with 55 nM AR, alpha2-integrin expression was slightly increased; however, unlike the EGF case, adherens junctions remained intact. These differences in the ability of EGF and amphiregulin to affect cellular adhesion and migration may be significant factors influencing normal and tumor cell behavior.

  9. Junctional adhesion molecule (JAM-C deficient C57BL/6 mice develop a severe hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Lena Wyss

    Full Text Available The junctional adhesion molecule (JAM-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS has been poorly characterized to date. Here we show that JAM-C(-/- mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C(-/- mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C(-/- C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF circulation within the ventricular system of JAM-C(-/- mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3(rd ventricle in JAM-C(-/- C57BL/6 mice. Taken together, our study suggests that JAM-C(-/- C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C.

  10. Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus.

    Science.gov (United States)

    Wyss, Lena; Schäfer, Julia; Liebner, Stefan; Mittelbronn, Michel; Deutsch, Urban; Enzmann, Gaby; Adams, Ralf H; Aurrand-Lions, Michel; Plate, Karl H; Imhof, Beat A; Engelhardt, Britta

    2012-01-01

    The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C(-/-) mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C(-/-) mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C(-/-) C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C(-/-) mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3(rd) ventricle in JAM-C(-/-) C57BL/6 mice. Taken together, our study suggests that JAM-C(-/-) C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C.

  11. Receptor-like Molecules on Human Intestinal Epithelial Cells Interact with an Adhesion Factor from Lactobacillus reuteri.

    Science.gov (United States)

    Matsuo, Yosuke; Miyoshi, Yukihiro; Okada, Sanae; Satoh, Eiichi

    2012-01-01

    A surface protein of Lactobacillus reuteri, mucus adhesion-promoting protein (MapA), is considered to be an adhesion factor. MapA is expressed in L. reuteri strains and adheres to piglet gastric mucus, collagen type I, and human intestinal epithelial cells such as Caco-2. The aim of this study was to identify molecules that mediate the attachment of MapA from L. reuteri to the intestinal epithelial cell surface by investigating the adhesion of MapA to receptor-like molecules on Caco-2 cells. MapA-binding receptor-like molecules were detected in Caco-2 cell lysates by 2D-PAGE. Two proteins, annexin A13 (ANXA13) and paralemmin (PALM), were identified by MALDI TOF-MS. The results of a pull-down assay showed that MapA bound directly to ANXA13 and PALM. Fluorescence microscopy studies confirmed that MapA binding to ANXA13 and PALM was colocalized on the Caco-2 cell membrane. To evaluate whether ANXA13 and PALM are important for MapA adhesion, ANXA13 and PALM knockdown cell lines were established. The adhesion of MapA to the abovementioned cell lines was reduced compared with that to wild-type Caco-2 cells. These knockdown experiments established the importance of these receptor-like molecules in MapA adhesion.

  12. Detection of Adhesion Molecules on Inflamed Macrophages at Early-Stage Using SERS Probe Gold Nanorods

    Institute of Scientific and Technical Information of China (English)

    Dakrong Pissuwan; Yusuke Hattori

    2017-01-01

    In recent years, it has been shown that inflammatory biomarkers can be used as an effective signal for disease diagnoses. The early detection of these signals provides useful information that could prevent the occurrence of severe diseases. Here, we employed surface-enhanced Raman scattering (SERS) probe gold nanorods (GNRs) as a tool for the early detection of inflammatory molecules in inflamed cells. A murine macrophage cell line (Raw264.7) stimulated with lipopolysaccharide (LPS) was used as a model in this study. The prepared SERS probe GNRs containing 4-mercapto-benzoic acid as a Raman reporter to generate SERS signals were used for detection of intracellular adhesion molecule-1 (ICAM-1) in macrophages after treatment with LPS for varying lengths of time. Our results show that SERS probe GNRs could detect significant differences in the expression of ICAM-1 molecules in LPS-treated macrophages compared to those in untreated macrophages after only 1 h of LPS treatment. In contrast, when using fluorescent labeling or enzyme-linked immunosorbent assays (ELISA) to detect ICAM-1, significant differences between inflamed and un-inflamed macrophages were not seen until the cells had been treated with LPS for 5 h. These results indicate that our SERS probe GNRs provide a higher sensitivity for detecting biomarker molecules in inflamed macrophages than the conventional fluorescence and ELISA techniques, and could therefore be useful as a potential diagnostic tool for managing disease risk.

  13. Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells.

    Science.gov (United States)

    Jung, J Y; Woo, S M; Kim, W J; Lee, B N; Nör, J E; Min, K S; Choi, C H; Koh, J T; Lee, K J; Hwang, Y C

    2017-04-01

    To investigate the effect of simvastatin on lipopolysaccharide (LPS)-stimulated inflammatory cytokines, cell adhesion molecules and nuclear factor-κB (NF-κB) transcription factors in human dental pulp cells (HDPCs). The effect of LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using a 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) assay. The expression of inflammatory cytokines and cell adhesion molecules was evaluated by reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. NF-κB transcription factors were evaluated by Western blot analysis. Statistical analysis was performed with analysis of variance (anova). The viability of cells exposed to different concentrations of E. coli LPS, P. gingivalis LPS and simvastatin was not significantly different compared with that of control cells (P > 0.05). LPS significantly increased interleukin (IL)-1β (P adhesion molecule-1 (VCAM-1) (P adhesion molecule-1 (ICAM-1) protein expression (P adhesion molecules and NF-κB transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp-capping agent in vital pulp therapy. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  15. Circulating adhesion molecules in patients with virus-related chronic diseases of the liver

    Institute of Scientific and Technical Information of China (English)

    Cosimo Marcello Bruno; Claudio Sciacca; Danila Cilio; Gaetano Bertino; Anna Elisa Marchese; Gaetana Politi; Lucia Chinnici

    2005-01-01

    AIM: In the inflammatory state, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) play a key role in promoting migration of immunological cells from the circulation to target site.Aim of our study was to investigate soluble forms of these molecules in patients with virus-related chronic liver diseases, to assess their behavior in different pathologies and correlation with severity of liver damage.METHODS: Circulating ICAM-1 and VCAM-1 were assayed by EIA commercial kits (R&D System Co.,Abington, UK) in 23 patients with chronic active hepatitis (CH), 50 subjects affected by liver cirrhosis (LC) and 15 healthy controls comparable for sex and age. In patients, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also detected by autoanalyzer.RESULTS: LC patients had significantly higher ICAM-1 values than CH patients (38.56±7.4 ng/mL vs 20.89±6.42 ng/mL; P<0.001) and these ones had significantly higher values than controls (12.92±1.08 ng/mL; P<0.001). In CH group, ICAM-1 levels were significantly related to inflammatory activity (P= 0.041) and ALT values (r= 0.77;P<0.05). VCAM-1 values were significantly increased only in LC patients (P<0.001) and related to severity of liver impairment.CONCLUSION: These findings suggest that the determination of serum ICAM-1 can be considered as an additional useful marker of hepatocellular necrosis and inflammatory activity in chronic hepatitis, while serum VCAM-1 is an indicator of liver fibrogenesis and severity of disease in cirrhosis.

  16. Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Stopp, Sabine; Bornhäuser, Martin; Ugarte, Fernando; Wobus, Manja; Kuhn, Matthias; Brenner, Sebastian; Thieme, Sebastian

    2013-04-01

    The melanoma cell adhesion molecule defines mesenchymal stromal cells in the human bone marrow that regenerate bone and establish a hematopoietic microenvironment in vivo. The role of the melanoma cell adhesion molecule in primary human mesenchymal stromal cells and the maintenance of hematopoietic stem and progenitor cells during ex vivo culture has not yet been demonstrated. We applied RNA interference or ectopic overexpression of the melanoma cell adhesion molecule in human mesenchymal stromal cells to evaluate the effect of the melanoma cell adhesion molecule on their proliferation and differentiation as well as its influence on co-cultivated hematopoietic stem and progenitor cells. Knockdown and overexpression of the melanoma cell adhesion molecule affected several characteristics of human mesenchymal stromal cells related to osteogenic differentiation, proliferation, and migration. Furthermore, knockdown of the melanoma cell adhesion molecule in human mesenchymal stromal cells stimulated the proliferation of hematopoietic stem and progenitor cells, and strongly reduced the formation of long-term culture-initiating cells. In contrast, melanoma cell adhesion molecule-overexpressing human mesenchymal stromal cells provided a supportive microenvironment for hematopoietic stem and progenitor cells. Expression of the melanoma cell adhesion molecule increased the adhesion of hematopoietic stem and progenitor cells to human mesenchymal stromal cells and their migration beneath the monolayer of human mesenchymal stromal cells. Our results demonstrate that the expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells determines their fate and regulates the maintenance of hematopoietic stem and progenitor cells through direct cell-cell contact.

  17. The neural cell adhesion molecule L1 is distinct from the N-CAM related group of surface antigens BSP-2 and D2

    DEFF Research Database (Denmark)

    Faissner, A; Kruse, J; Goridis, C

    1984-01-01

    The neural cell adhesion molecule L1 and the group of N-CAM related molecules, BSP-2 and D2 antigen, are immunochemically distinct molecular species. The two groups of surface molecules are also functionally distinct entities, since inhibition of Ca2+-independent adhesion among early post...

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

    Science.gov (United States)

    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.

  19. Mechanisms of transcriptional regulation and prognostic significance of activated leukocyte cell adhesion molecule in cancer

    Directory of Open Access Journals (Sweden)

    Chen Hairu

    2010-10-01

    Full Text Available Abstract Background Activated leukocyte cell adhesion molecule (ALCAM is implicated in the prognosis of multiple cancers with low level expression associated with metastasis and early death in breast cancer. Despite this significance, mechanisms that regulate ALCAM gene expression and ALCAM's role in adhesion of pre-metastatic circulating tumor cells have not been defined. We studied ALCAM expression in 20 tumor cell lines by real-time PCR, western blot and immunochemistry. Epigenetic alterations of the ALCAM promoter were assessed using methylation-specific PCR and bisulfite sequencing. ALCAM's role in adhesion of tumor cells to the vascular wall was studied in isolated perfused lungs. Results A common site for transcription initiation of the ALCAM gene was identified and the ALCAM promoter sequenced. The promoter contains multiple cis-active elements including a functional p65 NF-κB motif, and it harbors an extensive array of CpG residues highly methylated exclusively in ALCAM-negative tumor cells. These CpG residues were modestly demethylated after 5-aza-2-deoxycytidine treatment. Restoration of high-level ALCAM expression using an ALCAM cDNA increased clustering of MDA-MB-435 tumor cells perfused through the pulmonary vasculature of ventilated rat lungs. Anti-ALCAM antibodies reduced the number of intravascular tumor cell clusters. Conclusion Our data suggests that loss of ALCAM expression, due in part to DNA methylation of extensive segments of the promoter, significantly impairs the ability of circulating tumor cells to adhere to each other, and may therefore promote metastasis. These findings offer insight into the mechanisms for down-regulation of ALCAM gene expression in tumor cells, and for the positive prognostic value of high-level ALCAM in breast cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

    Directory of Open Access Journals (Sweden)

    Qian-ru He

    2016-01-01

    Full Text Available The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A mRNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration.

  2. PRIMING EFFECT OF HOMOCYSTEINE ON INDUCIBLE VASCULAR CELL ADHESION MOLECULE-1 EXPRESSION IN ENDOTHELIAL CELLS

    Science.gov (United States)

    Séguin, Chantal; Abid, Md. Ruhul; Spokes, Katherine C.; Schoots, Ivo G; Brkovic, Alexandre; Sirois, Martin G.; Aird, William C.

    2017-01-01

    Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis, as well as for arterial and venous thrombosis. However, the mechanisms through which elevated circulating levels of homocysteine cause vascular injury and promote thrombosis remain unclear. Here, we tested the hypothesis that homocysteine (Hcy) sensitizes endothelial cells to the effect of inflammatory mediators. Human umbilical vein endothelial cells (HUVEC) were incubated with Hcy 1.0 mM for varying time points, and then treated in the absence or presence of 1.5 U/ml thrombin or 10 ng/ml lipopolysaccharide (LPS). Hcy alone had no effect on the expression of vascular cell adhesion molecule (VCAM)-1. However, Hcy enhanced thrombin- and LPS-mediated induction of VCAM-1 mRNA and protein levels. Consistent with these results, pretreatment of HUVEC with Hcy resulted in a two-fold increase in LSP-mediated induction of leukocyte adhesion. The latter effect was significantly inhibited by anti-VCAM-1 antibodies. Together, these findings suggest that Hcy sensitizes HUVEC to the effect of inflammatory mediators thrombin and LPS, at least in part through VCAM-1 expression and function. PMID:18406566

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

    Science.gov (United States)

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

    2008-11-15

    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 cells of the stratum intermedium (SI), its absence in nectin-1-null mice correlated with separation of the cell layers at this interface. Numerous, large desmosomes were present at this interface in wild-type mice; however, where adhesion persisted in the mutant mice, the desmosomes were smaller and less numerous. Nectins have been shown to regulate tight junction formation; however, this is the first report showing that they may also participate in the regulation of desmosome assembly. Importantly, our results show that integrity of the SI-ameloblast interface is essential for normal enamel mineralization.

  4. A multivariate analysis of adhesion molecules expression in assessment of colorectal cancer.

    Science.gov (United States)

    Ngan, Chew Yee; Yamamoto, Hirofumi; Seshimo, Iwao; Ezumi, Koji; Terayama, Motokazu; Hemmi, Hideyuki; Takemasa, Ichiro; Ikeda, Masataka; Sekimoto, Mitsugu; Monden, Morito

    2007-06-15

    Adhesion molecules are implicated in the progression of colorectal cancer (CRC). Despite the evidence of association between their expression and patients' prognosis, the data have not been examined simultaneously in a same study; thus, the relative clinical value remained largely unknown. The aim of this study was to identify the adhesion factors that display the most significant prognostic value for CRC patients to guide clinical decision-making regarding appropriate treatment. We examined by immunohistochemistry, the expression of E-cadherin and its associated catenins, alpha(alpha)-catenin and beta(beta)-catenin, DCC, and CD44 and its partner, MT1-MMP in a series of 140 CRC tissues at intermediate Stage II and Stage III to determine their prognostic significance. Clinicopathological survey indicated an inverse relationship between E-cadherin expression and tumor differentiation, and an association between CD44 expression and venous invasion. Univariate and multivariate analyses showed that loss of expression of E-cadherin and CD44 significantly correlated to poor survival, especially in Stage II. Combination studies indicated that loss of E-cadherin and loss of CD44 had the worst impact on patient prognosis, particularly in colon cancer. Immunohistochemical staining of E-cadherin and CD44 may help to identify a subgroup of high-risk patients with Stage II CRC, especially in colon cancer, who may need intensive follow-up and appropriate therapeutic strategy. Copyright 2007 Wiley-Liss, Inc.

  5. Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma

    Science.gov (United States)

    Liu, Ju-Fang; Tsao, Ya-Ting; Hou, Chun-Han

    2015-01-01

    Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression. PMID:26503469

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

    DEFF Research Database (Denmark)

    Nybroe, O; Albrechtsen, M; Dahlin, J;

    1985-01-01

    and a 115,000 Mr polypeptide C, whereas neurons expressed a 200,000 Mr polypeptide A as well as polypeptide B. Skeletal muscle cells produced polypeptide B. The polypeptides synthesized by the three cell types were immunochemically identical. The membrane association of polypeptide C was investigated......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...... with methods that distinguish peripheral and integral membrane proteins. Polypeptide C was found to be a peripheral membrane protein, whereas polypeptides A and B were integral membrane proteins with cytoplasmic domains of approximately 50,000 and approximately 25,000 Mr, respectively. The affinity...

  7. Testicular cell adhesion molecule 1 (TCAM1) is not essential for fertility

    Science.gov (United States)

    Nalam, Roopa L.; Lin, Yi-Nan; Matzuk, Martin M.

    2009-01-01

    Testicular cell adhesion molecule 1 (Tcam1) is a testis-expressed gene that is evolutionarily conserved in most mammalian species. The putative location of TCAM1 on the cell surface makes it an attractive contraceptive target to study. We found that Tcam1 transcription is enriched in the adult testis, and in situ hybridization revealed that Tcam1 is expressed in pachytene to secondary spermatocytes. Immunofluorescence for TCAM1 protein showed strong expression along cell membranes of spermatocytes and weak localization to round spermatids. In light of this evidence, we hypothesized that TCAM1 interacts with an unknown receptor on the surface of Sertoli cells and that this interaction is important for germ cell-Sertoli cell interactions. However, Tcam1 knockout mice that we generated are fertile, and testis weights and sperm counts were not significantly altered. Therefore, we conclude that TCAM1 is not essential for male fertility or germ cell function in Mus musculus. PMID:19766163

  8. Temporal and spacial changes of highly polysialylated neural cell adhesion molecule immunoreactivity in amygdala kindling development.

    Science.gov (United States)

    Sato, K; Iwai, M; Nagano, I; Shoji, M; Abe, K

    2003-01-01

    To investigate the migration of neural stem cells as well as neural plastic changes in epileptic brain, spaciotemporal expression of immunoreactive highly polysialylated neural cell adhesion molecule (PSA-NCAM) was examined in amygdala kindling development of rat. The neural migration and synaptic remodeling detected with PSA-NCAM staining occurred in dentate gyrus of hippocampus, subventricular zone and pyriform cortex with amygdaloid kindling in generalized seizure but not in partial seizure. Although PSA-NCAM positive dendrite in dentate gyrus was minimally found in the control brain, it extended slightly in animals with partial seizure, and greatly toward the molecular layer with generalized seizure. Thus, the migration of neural stem cells as well as neural plastic changes were specially and temporally different between brain regions depending on different kindling stages. These changes may mainly contribute to the reorganization of neural network in epileptic brain.

  9. Changes in lymphocyte subpopulations and adhesion/activation molecules following endotoxemia and major surgery

    DEFF Research Database (Denmark)

    Toft, P; Hokland, Marianne; Hansen, Tom Giedsing

    1995-01-01

    Major surgery as well as endotoxin-induced sepsis is accompanied by lymphocytopenia in peripheral blood. The purpose of this study was to investigate the redistribution of lymphocyte subpopulations and adhesion/activation molecules on lymphocytes. Twenty-four rats were included in the investigation....... Eight rats received an intraperitoneal injection of E. coli endotoxin (2 mg kg-1), eight rats had a sham operation performed while eight rats received isotonic saline and served as a control group. Blood samples were obtained by making an incision in the tail before and 2 and 5 h after surgery...... or administration of endotoxin or saline. After isolation of lymphocytes by gradient centrifugation, flow-cytometric immunophenotyping was performed using CD2, CD3, CD4, CD8, CD11/CD18, CD20, CD44 and MHC II monoclonal antibodies. Endotoxemia and surgery were both accompanied by increased serum cortisol...

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

    DEFF Research Database (Denmark)

    1993-01-01

    report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM...... 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......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...

  11. Chromosomal mapping of the structural gene coding for the mouse cell adhesion molecule uvomorulin

    Energy Technology Data Exchange (ETDEWEB)

    Eistetter, H.R.; Adolph, S.; Ringwald, M.; Simon-Chazottes, D.; Schuh, R.; Guenet, J.L.; Kemler, R. (Max-Planck-Gesellschaft, Tuebingen (West Germany))

    1988-05-01

    The gene coding for the mouse cell adhesion molecule uvomorulin has been mapped to chromosome 8. Uvomorulin cDNA clone F5H3 identified restriction fragment length polymorphisms in Southern blots of genomic DNA from mouse species Mus musculus domesticus and Mus spretus. By analyzing the segregation pattern of the gene in 75 offspring from an interspecific backcross a single genetic locus, Um, was defined on chromosome 8. Recombination frequency between Um and the co-segregating loci serum esterase 1 (Es-1) and tyrosine aminotransferase (Tat) places Um about 14 centimorgan (cM) distal to Es-1, and 5 cM proximal to Tat. In situ hybridization of uvomorulin ({sup 3}H)cDNA to mouse metaphase chromosomes located the Um locus close to the distal end of chromosome 8 (bands C3-E1). Since uvomorulin is evolutionarily highly conserved, its chromosomal assignment adds an important marker to the mouse genetic map.

  12. Identification of DNA aptamers toward epithelial cell adhesion molecule via cell-SELEX.

    Science.gov (United States)

    Kim, Ji Won; Kim, Eun Young; Kim, Sun Young; Byun, Sang Kyung; Lee, Dasom; Oh, Kyoung-Jin; Kim, Won Kon; Han, Baek Soo; Chi, Seung-Wook; Lee, Sang Chul; Bae, Kwang-Hee

    2014-10-31

    The epithelial cell adhesion molecule (EpCAM, also known as CD326) is a transmembrane glycoprotein that is specifically detected in most adenocarcinomas and cancer stem cells. In this study, we performed a Cell systematic evolution of ligands by exponential enrichment (SELEX) experiment to isolate the aptamers against EpCAM. After seven round of Cell SELEX, we identified several aptamer candidates. Among the selected aptamers, EP166 specifically binds to cells expressing EpCAM with an equilibrium dissociation constant (Kd) in a micromolar range. On the other hand, it did not bind to negative control cells. Moreover, EP166 binds to J1ES cells, a mouse embryonic stem cell line. Therefore, the isolated aptamers against EpCAM could be used as a stem cell marker or in other applications in both stem cell and cancer studies.

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

    DEFF Research Database (Denmark)

    Edvardsen, K; Pedersen, P H; Bjerkvig, R

    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...... of the injection site, with a sharply demarcated border between the tumor and brain tissue. In contrast, the parental cell line showed single-cell infiltration and more pronounced destruction of normal brain tissue. Using a 51Cr-release assay, spleen cells from rats transplanted with BT4Cn tumor cells generally...... 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...

  14. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE-1 BY MYOFIBERS IN mdx MICE

    Science.gov (United States)

    TORRES-PALSA, MARIA J.; KOZIOL, MATTHEW V.; GOH, QINGNIAN; CICINELLI, PETER A.; PETERSON, JENNIFER M.; PIZZA, FRANCIS X.

    2017-01-01

    Introduction We investigated the extent to which intercellular adhesion molecule-1 (ICAM-1), a critical protein of the inflammatory response, is expressed in skeletal muscles of mdx mice (a murine model of Duchenne muscular dystrophy). Methods Muscles were collected from control and mdx mice at 2–24 weeks of age and analyzed for ICAM-1 expression by means of Western blot and immunofluorescence. Results Western blot revealed higher expression of ICAM-1 in mdx compared with control muscles through 24 weeks of age. In contrast to control muscles, ICAM-1 was expressed on the membrane of damaged, regenerating, and normal myofibers of mdx mice. CD11b+ myeloid cells also expressed ICAM-1 in mdx muscles, and CD11b+ cells were closely associated with the membrane of myofibers expressing ICAM-1. Conclusions These findings support a paradigm in which ICAM-1 and its localization to myofibers in muscles of mdx mice contributes to the dystrophic pathology. PMID:25728314

  15. Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

    OpenAIRE

    Qian-ru He; Meng Cong; Qing-zhong Chen; Ya-feng Sheng; Jian Li; Qi Zhang; Fei Ding; Yan-pei Gong

    2016-01-01

    The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A mRNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecul...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Expression and induction of costimulatory and adhesion molecules on acute myeloid leukemic cells: implications for adoptive immunotherapy.

    Science.gov (United States)

    Brouwer, R E; Zwinderman, K H; Kluin-Nelemans, H C; van Luxemburg-Heijs, S A; Willemze, R; Falkenburg, J H

    2000-02-01

    Previously, we observed an increased recognition of malignant cells by cytotoxic T lymphocytes (CTL) when the target cells were cultured in vitro for 24 hours. In this study, we analyzed the expression of costimulatory and adhesion molecules on acute myeloid leukemia (AML) cells and determined whether 24-hour culture of the cells was associated with upregulation of these molecules. We analyzed whether this incubation period improved recognition of AML cells by CTL. Expression of costimulatory and adhesion molecules on leukemic blasts of 34 patients comprising each AML FAB subclassification were analyzed directly and after 24 hours of culture, and the recognition of these AML cells by an HLA-A2 restricted CTL clone was determined. Blocking studies were performed with antibodies against CD54, CD58, and CD11a. Immunophenotyping showed a low expression of CD80 and CD40 and a variable CD86 expression on most AML cells. CD54 expression was generally low, CD58 expression was high, and CD11a expression was variable, with a higher expression in AML M0, M1, M4, and M5. Twenty-four hours of culture resulted in a significant upregulation of CD40, CD54, and CD58. Impaired recognition of AML cells by the HLA-A2 restricted CTL clone was enhanced 100-200% by 24 hours of preincubation of the leukemic cells. Blocking studies showed the importance of multiple adhesion molecules on the AML cells. Low expression of multiple costimulatory and adhesion molecules on AML could be upregulated by 24 hours of culture, which was associated with increased recognition of the AML blasts by CTL. Blocking multiple adhesion molecules completely abolished CTL recognition, showing the importance of the combination of these molecules for T-cell interaction with AML.

  20. Stability of lyophilized human platelets loaded with small molecule carbohydrates.

    Science.gov (United States)

    Wang, J X; Yang, C; Wan, W; Liu, M X; Ren, S P; Quan, G B; Han, Y

    2011-01-01

    Long-term preservation of platelets is a great challenge for blood transfusion centers, due to the required narrow storage temperature arange (22 ± 2 degree C). Short shelf life and potential bacterial growth often lead to the shortage of high-quality platelets. Freeze-dried preservation is thus believed to be a potential solution for long-term platelet storage without losing the hemostasis function. Here we report a new platelet preservation method, which uses small molecule carbohydrates to extend storage time and to maintain platelet function. The activities of lyophilized platelets that were stabilized with small molecule carbohydrate (e.g., cell viability, mean platelet volume, activation characteristics, and aggregation kinetics) were maintained after storage of 30, 60, and 90 days at room temperature, 4 degree C, and -20 degree C. The recovery of freeze-dried platelets was 87 percent in comparison to fresh platelets. The mean platelet volume of rehydrated platelets increased (from 6.8 fl to 8.0 fl). About 40 percent of rehydrated platelets was in the early-activated stage (PCA-1 positive) and 30 percent was in the terminal-activated stage (CD62P positive). The cell viability was about 60 percent as measured with CMFDA vital probes. The aggregation rate of rehydrated platelets after 90-day storage was similar to fresh platelets stored at 22 degree C ± 2 degree C.

  1. Thermodynamic Stability of Structure H Hydrates Based on the Molecular Properties of Large Guest Molecules

    Directory of Open Access Journals (Sweden)

    Ryo Ohmura

    2012-02-01

    Full Text Available This paper report analyses of thermodynamic stability of structure-H clathrate hydrates formed with methane and large guest molecules in terms of their gas phase molecular sizes and molar masses for the selection of a large guest molecule providing better hydrate stability. We investigated the correlation among the gas phase molecular sizes, the molar masses of large molecule guest substances, and the equilibrium pressures. The results suggest that there exists a molecular-size value for the best stability. Also, at a given molecule size, better stability may be available when the large molecule guest substance has a larger molar mass.

  2. Self-assembled monolayer of designed and synthesized triazinedithiolsilane molecule as interfacial adhesion enhancer for integrated circuit

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2011-01-01

    Full Text Available Abstract Self-assembled monolayer (SAM with tunable surface chemistry and smooth surface provides an approach to adhesion improvement and suppressing deleterious chemical interactions. Here, we demonstrate the SAM comprising of designed and synthesized 6-(3-triethoxysilylpropylamino-1,3,5-triazine-2,4-dithiol molecule, which can enhance interfacial adhesion to inhibit copper diffusion used in device metallization. The formation of the triazinedithiolsilane SAM is confirmed by X-ray photoelectron spectroscopy. The adhesion strength between SAM-coated substrate and electroless deposition copper film was up to 13.8 MPa. The design strategy of triazinedithiolsilane molecule is expected to open up the possibilities for replacing traditional organosilane to be applied in microelectronic industry.

  3. Self-assembled monolayer of designed and synthesized triazinedithiolsilane molecule as interfacial adhesion enhancer for integrated circuit.

    Science.gov (United States)

    Wang, Fang; Li, Yanni; Wang, Yabin; Cao, Zhuo

    2011-08-03

    Self-assembled monolayer (SAM) with tunable surface chemistry and smooth surface provides an approach to adhesion improvement and suppressing deleterious chemical interactions. Here, we demonstrate the SAM comprising of designed and synthesized 6-(3-triethoxysilylpropyl)amino-1,3,5-triazine-2,4-dithiol molecule, which can enhance interfacial adhesion to inhibit copper diffusion used in device metallization. The formation of the triazinedithiolsilane SAM is confirmed by X-ray photoelectron spectroscopy. The adhesion strength between SAM-coated substrate and electroless deposition copper film was up to 13.8 MPa. The design strategy of triazinedithiolsilane molecule is expected to open up the possibilities for replacing traditional organosilane to be applied in microelectronic industry.

  4. Self-assembled monolayer of designed and synthesized triazinedithiolsilane molecule as interfacial adhesion enhancer for integrated circuit

    Science.gov (United States)

    2011-01-01

    Self-assembled monolayer (SAM) with tunable surface chemistry and smooth surface provides an approach to adhesion improvement and suppressing deleterious chemical interactions. Here, we demonstrate the SAM comprising of designed and synthesized 6-(3-triethoxysilylpropyl)amino-1,3,5-triazine-2,4-dithiol molecule, which can enhance interfacial adhesion to inhibit copper diffusion used in device metallization. The formation of the triazinedithiolsilane SAM is confirmed by X-ray photoelectron spectroscopy. The adhesion strength between SAM-coated substrate and electroless deposition copper film was up to 13.8 MPa. The design strategy of triazinedithiolsilane molecule is expected to open up the possibilities for replacing traditional organosilane to be applied in microelectronic industry. PMID:21812994

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein...

  6. The Neural Cell Adhesion Molecule-Derived Peptide FGL Facilitates Long-Term Plasticity in the Dentate Gyrus in Vivo

    Science.gov (United States)

    Dallerac, Glenn; Zerwas, Meike; Novikova, Tatiana; Callu, Delphine; Leblanc-Veyrac, Pascale; Bock, Elisabeth; Berezin, Vladimir; Rampon, Claire; Doyere, Valerie

    2011-01-01

    The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as…

  7. The Neural Cell Adhesion Molecule-Derived Peptide FGL Facilitates Long-Term Plasticity in the Dentate Gyrus in Vivo

    Science.gov (United States)

    Dallerac, Glenn; Zerwas, Meike; Novikova, Tatiana; Callu, Delphine; Leblanc-Veyrac, Pascale; Bock, Elisabeth; Berezin, Vladimir; Rampon, Claire; Doyere, Valerie

    2011-01-01

    The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as…

  8. An immunohistochemical evaluation of cell adhesion molecules in human dental pulp after tooth preparation and application of temporary luting cements.

    Science.gov (United States)

    Bagis, Bora; Atilla, Pergin; Cakar, Nur; Hasanreisoglu, Ufuk

    2009-01-01

    The aim of this study was to determine if temporary luting cements used with provisional restorations alter the expression of cell adhesion molecules (CAMs) in human dental pulp. Twenty-five healthy human premolars and third molars scheduled to be extracted for orthodontic reasons were randomly assigned to 5 experimental groups. Group 1 included untreated teeth as negative control. In groups 2-5, provisional crowns were cemented to the prepared teeth with either eugenol-containing or eugenol-free temporary cement and extracted 24 or 48 h after the treatment. Expression ratio and staining intensity of CAMs, including E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial cell adhesion molecule 1 (PECAM-1), was investigated in the pulp samples. The assessment of immunohistochemical reactions was performed by 2 independent observers using a semiquantitative scale. Significant reductions were recorded in the expression ratio and/or the staining intensity of E-selectin, ICAM-1, and VCAM-1 in samples removed 48 h after treatment with eugenol-containing cement compared with intact teeth. This reduction was significant only for ICAM-1 for 48-h eugenol-free samples. Moreover, the eugenol-free cement group indicated considerably higher E-selectin, ICAM-1, and VCAM-1 expression compared with the eugenol-containing group (P dental pulp.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein ki...

  10. Distribution of cytoskeletal proteins, integrins, leukocyte adhesion molecules and extracellular matrix proteins in plastic-embedded human and rat kidneys

    NARCIS (Netherlands)

    van Goor, H; Coers, W; van der Horst, MLC; Suurmeijer, AJH

    2001-01-01

    OBJECTIVE: To study the distribution of cytoskeletal proteins (actin, alpha -actinin, vinculin, beta -tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-6], beta1, beta2 [CD18], vitronectin receptor [alphav beta3], CD 11b), leukocyte adhesi

  11. N-glycosylation controls the function of junctional adhesion molecule-A.

    Science.gov (United States)

    Scott, David W; Tolbert, Caitlin E; Graham, David M; Wittchen, Erika; Bear, James E; Burridge, Keith

    2015-09-15

    Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein expressed by endothelial and epithelial cells. JAM-A serves many roles and contributes to barrier function and cell migration and motility, and it also acts as a ligand for the leukocyte receptor LFA-1. JAM-A is reported to contain N-glycans, but the extent of this modification and its contribution to the protein's functions are unknown. We show that human JAM-A contains a single N-glycan at N185 and that this residue is conserved across multiple mammalian species. A glycomutant lacking all N-glycans, N185Q, is able to reach the cell surface but exhibits decreased protein half-life compared with the wild- type protein. N-glycosylation of JAM-A is required for the protein's ability to reinforce barrier function and contributes to Rap1 activity. We further show that glycosylation of N185 is required for JAM-A-mediated reduction of cell migration. Finally, we show that N-glycosylation of JAM-A regulates leukocyte adhesion and LFA-1 binding. These findings identify N-glycosylation as critical for JAM-A's many functions. © 2015 Scott et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Immunohistochemistry of adhesion molecules, metalloproteinases and NO-synthases in extravillous trophoblast of tubal pregnancy.

    Science.gov (United States)

    Dubernard, G; Galtier-Fougairolles, M; Cortez, A; Uzan, S; Challier, J C

    2005-12-12

    Trophoblast invasion in uterine pregnancy is fine-tuned for the remodelling of the uterine wall and its vascularization. Tubal pregnancy, which occurs in a limited number of patients, involves a dramatic trophoblast invasion in a context of a poor decidualization. By studying the histology of the extravillous trophoblast (EVC) in the anchoring villi, the Ki67 labelling, the location of several adhesion markers (cytokeratin-7, alpha1, alpha6, alphaV, beta1, beta4 integrin subunits and E-cadherin, V/E-cadherin), metalloproteinases (MMP-2, 9 and11), NOS2 and 3, we aimed to detect the specificity of tubal compared to intrauterine pregnancies. No difference could be observed between meso or anti-salpingial trophoblast proliferation or invasion using Ki67. Cytokeratin-7 allowed detection of spindle-shape EVCs and we identified some decidualized stromal cells. Integrins alpha1, beta1 and alphaV, and V/E-cadherin were expressed mainly in the distal EVC correspondingly to intrauterine pregnancy, with a poor expression of alpha1. Integrins alpha6 and beta4, E-cadherin were detected in the distal EVC in contrast to uterine pregnancy. MMP-2, 9, 11 were also shown in distal EVC. NOS2 and 3 labelled the perivascular EVC and NOS3 the endothelial cells of the tubal vessels. These changed distributions of adhesion molecules and MMP together with that of the basic and inducible NOS expressions could be related to mechanical effects in superficial implantation or to a failure of decidualization in tubal pregnancies.

  13. Effect of soy nuts on adhesion molecules and markers of inflammation in hypertensive and normotensive postmenopausal women.

    Science.gov (United States)

    Nasca, Melita M; Zhou, Jin-Rong; Welty, Francine K

    2008-07-01

    Recently, it was shown that substituting soy nuts for nonsoy protein in a therapeutic lifestyle change (TLC) diet lowered systolic and diastolic blood pressure by 9.9% and 6.8%, respectively, in postmenopausal women with hypertension and by 5.2% and 2.9%, respectively, in normotensive postmenopausal women. In this study, to examine mechanisms for these reductions, markers of inflammation were measured, including soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, C-reactive protein, interleukin-6, and matrix metalloproteinase-9. Sixty healthy postmenopausal women (48 normotensive and 12 with hypertension) were randomized in a crossover design to a TLC diet alone or a TLC diet in which 0.5 cups of soy nuts (25 g soy protein and 101 mg aglycone isoflavones) replaced 25 g of nonsoy protein daily. Each diet was followed for 8 weeks. Compared with the TLC diet alone, levels of soluble vascular cell adhesion molecule-1 were significantly lower on the soy diet in women with hypertension (623.6 +/- 153.8 vs 553.8 +/- 114.4 ng/ml, respectively, p = 0.003), whereas no significant differences were observed in normotensive women. Soy nuts were associated with a trend toward reduction in C-reactive protein in normotensive women. No effect on levels of soluble intercellular adhesion molecule-1, interleukin-6, or matrix metalloproteinase-9 was observed. In conclusion, the reduction in soluble vascular cell adhesion molecule-1 with soy nuts in women with hypertension suggests an improvement in endothelial function that may reflect an overall improvement in the underlying inflammatory process underlying atherosclerosis.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. Co-localization of neural cell adhesion molecule and fibroblast growth factor receptor 2 in early embryo development.

    Science.gov (United States)

    Vesterlund, Liselotte; Töhönen, Virpi; Hovatta, Outi; Kere, Juha

    2011-01-01

    During development there is a multitude of signaling events governing the assembly of the developing organism. Receptors for signaling molecules such as fibroblast growth factor receptor 2 (FGFR2) enable the embryo to communicate with the surrounding environment and activate downstream pathways. The neural cell adhesion molecule (NCAM) was first characterized as a cell adhesion molecule highly expressed in the nervous system, but recent studies have shown that it is also a signaling receptor. Using a novel single oocyte adaptation of the proximity ligation assay, we here show a close association between NCAM and FGFR2 in mouse oocytes and 2-cell embryos. Real-time PCR analyses revealed the presence of messenger RNA encoding key proteins in downstream signaling pathways in oocytes and early mouse embryos. In summary these findings show a co-localization of NCAM and FGFR2 in early vertebrate development with intracellular signaling pathways present to enable a cellular response.

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

    Science.gov (United States)

    Zhong, Xia; Li, Xiaonan; Liu, Fuli; Tan, Hui; Shang, Deya

    2012-08-24

    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.

  18. The adhesion molecule PECAM-1 enhances the TGFβ-mediated inhibition of T cell function

    Science.gov (United States)

    Newman, Debra K.; Fu, Guoping; Adams, Tamara; Cui, Weiguo; Arumugam, Vidhyalakshmi; Bluemn, Theresa; Riese, Matthew J.

    2016-01-01

    Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that inhibits the pro-inflammatory functions of T cells, and it is a major factor in abrogating T cell activity against tumors. Canonical signaling results in the activation of Smad proteins, transcription factors that regulate target gene expression. Here, we found that the cell surface molecule platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitates non-canonical (Smad-independent) TGF-β signaling in T cells. Subcutaneously injected tumor cells dependent on TGF-β-mediated suppression of immunity grew more slowly in PECAM-1−/− mice than in their wild type counterparts. T cells isolated from PECAM-1−/− mice demonstrated relative insensitivity to the TGF-β-dependent inhibition of interferon- γ (IFN-γ) production, granzyme B synthesis and cellular proliferation. Similarly, human T cells lacking PECAM-1 demonstrated decreased sensitivity to TGF-β in a manner that was partially restored by re-expression of PECAM-1. Co-incubation of T cells with TGF-β and a T cell-activating antibody resulted in PECAM-1 phosphorylation on an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the recruitment of the inhibitory Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2). Such stimulatory conditions also induced the co-localization of PECAM-1 with the TGF-β receptor complex as identified by co-immunoprecipitation, confocal microscopy, and proximity ligation assays. These studies indicate a role for PECAM-1 in enhancing the inhibitory functions of TGF-β in T cells and suggest that therapeutic targeting of the PECAM-1-TGF-β inhibitory axis represents a means to overcome TGF-β-dependent immunosuppression within the tumor microenvironment. PMID:26956486

  19. Long-term dispersion stability and adhesion promotion of aqueous Cu nano-ink for flexible printed electronics.

    Science.gov (United States)

    Seo, Yeong-Hui; Jeong, Sunho; Jo, Yejin; Choi, Youngmin; Ryu, Beyong-Hwan; Han, Gayoung; Lee, Minsu

    2013-08-01

    Aqueous Cu nanoparticles are synthesized using a reducing agent and surface capping molecule which prevents the interparticular agglomeration and surface oxidation. Aqueous conductive nano ink is prepared using the resulting Cu nanoparticles and conductive Cu layers are prepared via a wet coating process. The conductive Cu layers, metalized by annealing at 300 degrees C under vacuum atmosphere, exhibit excellent electrical resistivity, showing values as low as 12 microomega cm. The long-term dispersion stability for three months is monitored through an investigation on the rheological behavior of the conductive nano ink and the resistivity variation of the conductive Cu layer. The adhesion property of the conductive Cu layer is dramatically improved when using a primer-treated polyimide film, whereas the conductive Cu layer completely peels off on a pristine polyimide film. The epoxy-contained primer plays a critical role as an intermediary between the aqueous Cu nano ink and the polyimide film.

  20. NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease

    Science.gov (United States)

    Azeredo, E L; De Oliveira-Pinto, L M; Zagne, S M; Cerqueira, D I S; Nogueira, R M R; Kubelka, C F

    2006-01-01

    During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3−) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3−, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease. PMID:16412060

  1. Annexin A2 Acts as an Adhesion Molecule on the Endometrial Epithelium during Implantation in Mice.

    Science.gov (United States)

    Wang, Bing; Ye, Tian-Min; Lee, Kai-Fai; Chiu, Philip C N; Pang, Ronald T K; Ng, Ernest H Y; Yeung, William S B

    2015-01-01

    To determine the function of Annexin A2 (Axna2) in mouse embryo implantation in vivo, experimental manipulation of Axna2 activities was performed in mouse endometrial tissue in vivo and in vitro. Histological examination of endometrial tissues was performed throughout the reproduction cycle and after steroid treatment. Embryo implantation was determined after blockage of the Axna2 activities by siRNA or anti-Axna2 antibody. The expression of Axna2 immunoreactivies in the endometrial luminal epithelium changed cyclically in the estrus cycle and was upregulated by estrogen. After nidatory estrogen surge, there was a concentration of Axna2 immunoreactivities at the interface between the implanting embryo and the luminal epithelium. The phenomenon was likely to be induced by the implanting embryos as no such concentration of signal was observed in the inter-implantation sites and in pseudopregnancy. Knockdown of Axna2 by siRNA reduced attachment of mouse blastocysts onto endometrial tissues in vitro. Consistently, the number of implantation sites was significantly reduced after infusion of anti-Axna2 antibody into the uterine cavity. Steroids and embryos modulate the expression of Axna2 in the endometrial epithelium. Axna2 may function as an adhesion molecule during embryo implantation in mice.

  2. Relocalization of cell adhesion molecules during neoplastic transformation of human fibroblasts.

    Science.gov (United States)

    Belgiovine, Cristina; Chiodi, Ilaria; Mondello, Chiara

    2011-11-01

    Studying neoplastic transformation of telomerase immortalized human fibroblasts (cen3tel), we found that the transition from normal to tumorigenic cells was associated with the loss of growth contact inhibition, the acquisition of an epithelial-like morphology and a change in actin organization, from stress fibers to cortical bundles. We show here that these variations were paralleled by an increase in N-cadherin expression and relocalization of different adhesion molecules, such as N-cadherin, α-catenin, p-120 and β-catenin. These proteins presented a clear membrane localization in tumorigenic cells compared to a more diffuse, cytoplasmic distribution in primary fibroblasts and non-tumorigenic immortalized cells, suggesting that tumorigenic cells could form strong cell-cell contacts and cell contacts did not induce growth inhibition. The epithelial-like appearance of tumorigenic cells did not reflect a mesenchymal-epithelial transition; in fact, cen3tel cells expressed vimentin and did not express cytokeratins at all transformation stages. Moreover, they did not express epithelial proteins such as occluding and claudin-1. In contrast, ZO-1 showed higher levels and a more defined membrane localization in tumorigenic cells compared to non-tumorigenic cells; this confirms its role in adherens junction formation in mesenchymal cells and is in agreement with the strong cell-cell contact formation by neoplastically transformed cells. Finally, we found α-catenin and ZO-1 nuclear localization in non-transformed cells, suggestive of possible additional roles of these proteins besides cell junction formation.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    Three soluble neural cell adhesion molecule (NCAM) polypeptide classes of M(r) values 190,000 (NCAM-s1), 135,000 (NCAM-s2) and 115,000-110,000 (NCAM-s3) have been demonstrated in rat brain and cerebrospinal fluid [Krog, Olsen, Dalseg, Roth and Bock (1992) J. Neurochem. 59, 838-847]. NCAM-s3...... is known to arise from released glycosylphosphatidylinositol (GPI)-linked NCAM [He, Finne and Goridis (1987) J. Cell. Biol. 105, 2489-2500] as well as from extracellularly cleaved transmembrane NCAM isoforms [Nybroe, Linnemann and Bock (1989) J. Neurochem. 53, 1372-1378]. In this study the origin of NCAM......-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...

  4. Expression of CD11b as an adhesion molecule on neutrophils in children with Kawasaki disease.

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    Behzad Heidari

    2014-08-01

    Full Text Available Inflammation of blood vessels is a characteristic feature of Kawasaki disease. Neutrophils play a key role in the inflammatory responses where movement of neutrophils toward the site of inflammation depends on CD11b/CD18 expression as adhesion molecules on these cells. The purpose of this study was to investigate CD11b/CD18 expression in patients with Kawasaki disease upon diagnosis and after treatment.The study included 20 children with Kawasaki disease aged from 3 months to 8 years. Mean fluorescence intensity of CD11b levels on diagnosis and at 1-2 and 6 weeks after intravenous immunoglobulin (IVIG therapy was measured in these patients. Level of CD11b was measured in age-matched healthy children and febrile children (each 21 as negative and positive controls, respectively.Mean fluorescence intensity of CD11b in Kawasaki patients was lower than that of the control groups before and after 1-2 weeks of IVIG therapy. There were no significant differences in CD11b in Kawasaki patients either with aneurysm or without aneurysm. The CD11b levels at the diagnosis time and after treatment with IVIG in our patients with Kawasaki were lower than the control groups.

  5. Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity

    Science.gov (United States)

    Heinrich, Garrett; Muturi, Harrison T.; Rezaei, Khadijeh; Al-Share, Qusai Y.; DeAngelis, Anthony M.; Bowman, Thomas A.; Ghadieh, Hilda E.; Ghanem, Simona S.; Zhang, Deqiang; Garofalo, Robert S.; Yin, Lei; Najjar, Sonia M.

    2017-01-01

    Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species. PMID:28396653

  6. CD8: Adhesion Molecule, Co-Receptor and Immuno-Modulator

    Institute of Scientific and Technical Information of China (English)

    David K Cole; George F Gao

    2004-01-01

    CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes, which are important components in cellular immunity, esp. In the immune response to cancer and chronic infections. There are two forms of CD8,either as an αα homodimer or αβ heterodimer. It acts as an "assistant" or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor (αβTCR) and its ligand peptide major histocompatibility complex (pMHC). CD8 also binds to pMHC but away from the interface of pMHC and TCR contact, thereof no influence on the specificity of this interaction. If the TCR and CD8 bind to the same pMHC at the same time, CD8 is defined as a co-receptor, functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway; if CD8 binds to pMHC independently of the TCR, it is defined as an adhesion molecule. At present, the co-receptor function theory is dominated in the field.Recent study has also shown that murine CD8αα binds to TL antigen, an MHC homologue, therefore acts as an immuno-modulator. In this review, we discuss these current understandings of the three aspects of the CD8 functions and their structural basis.

  7. CD8: Adhesion Molecule, Co-Receptor and Immuno-Modulator

    Institute of Scientific and Technical Information of China (English)

    DavidKCole; GeorgeFGao

    2004-01-01

    CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes, which are important components in cellular immunity, esp. in the immune response to cancer and chronic infections. There are two forms of CD8, either as an αα homodimer or αβ heterodimer. It acts as an "assistant" or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor (αβTCR) and its ligand peptide major histocompatibility complex (pMHC). CD8 also binds to pMHC but away from the interface of pMHC and TCR contact, thereof no influence on the specificity of this interaction. If the TCR and CD8 bind to the same pMHC at the same time, CD8 is defined as a co-receptor, functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway; if CD8 binds to pMHC independently of the TCR, it is defined as an adhesion molecule. At present, the co-receptor function theory is dominated in the field. Recent study has also shown that murine CD8αα binds to TL antigen, an MHC homologue, therefore acts as an immuno-modulator. In this review, we discuss these current understandings of the three aspects of the CD8 functions and their structural basis. Cellular & Molecular Immunology. 2004;1(2):81-88.

  8. NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease.

    Science.gov (United States)

    Azeredo, E L; De Oliveira-Pinto, L M; Zagne, S M; Cerqueira, D I S; Nogueira, R M R; Kubelka, C F

    2006-02-01

    During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.

  9. Effect of thalidomide dithiocarbamate analogs on the intercellular adhesion molecule-1 expression.

    Science.gov (United States)

    Guirgis, Adel A; Zahran, Magdy A H; Mohamed, Amr S; Talaat, Roba M; Abdou, Bishoy Y; Agwa, Hussein S

    2010-07-01

    Thalidomide has been reported to have anti-angiogenic and antimetastatic effects. Intercellular adhesion molecule-1 (ICAM-1) was shown to be involved in monocyte adherence to epithelial cells and cancer cell invasion. Novel thalidomide dithiocarbamate analogs (containing 2 sulfur atoms) were designed and synthesized as potential anti-tumor agents. The aim of this work is to investigate their anti-tumor effect against transplantable experimental tumor, Ehrlich ascites carcinoma (EAC), in mice by studying the changes in cell's biochemical profile, the expression of ICAM-1 and nitric oxide (NO) and their association with tumor burden. As shown in our results, treatment of solid tumor-bearing mice with thalidomide 1 resulted in a significant reduction in tumor volume with 75.4% inhibition, a significant decrease in lactate dehydrogenase (LDH), ICAM-1 expression and NO. Thalidomide dithiocarbamate analogs 2 and 3 exhibited a potent effect to reduce the volume of solid tumor with 96.7% and 96.5% inhibition, respectively, a significant ability to increase the albumin, alanine aminotransferase (ALT) and glucose levels and to diminish LDH, ICAM-1 expression and NO. Thalidomide dithiocarbamate analog 3 has more potent anti-tumor activity as compared with thalidomide 1 or its dithiocarbamate analog 2. Taken together, our study improved that the dithiocarbamate analogs 2 and 3 are more potent anti-tumor agents with more pronounced effect than thalidomide 1 itself.

  10. Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma.

    Science.gov (United States)

    Xu, Linlin; Mohammad, Khalid S; Wu, Hao; Crean, Colin; Poteat, Bradley; Cheng, Yinghua; Cardoso, Angelo A; Machal, Christophe; Hanenberg, Helmut; Abonour, Rafat; Kacena, Melissa A; Chirgwin, John; Suvannasankha, Attaya; Srour, Edward F

    2016-12-01

    Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166(+) multiple myeloma cells homed more efficiently than CD166(-) cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells. CD166 deficiency in multiple myeloma cell lines or CD138(+) bone marrow cells from multiple myeloma patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Furthermore, CD166 deficiency in multiple myeloma cells also reduced the formation of osteolytic disease in vivo after intratibial engraftment. Mechanistic investigation revealed that CD166 expression in multiple myeloma cells inhibited osteoblastogenesis of bone marrow-derived osteoblast progenitors by suppressing Runx2 gene expression. Conversely, CD166 expression in multiple myeloma cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in multiple myeloma cell homing to the bone marrow and multiple myeloma progression, rationalizing its further study as a candidate therapeutic target for multiple myeloma treatment. Cancer Res; 76(23); 6901-10. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas

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    Nikolaos Koletsas

    2017-01-01

    Full Text Available Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs. Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections. The immunohistochemical results were correlated with clinicopathological parameters. Results. The overexpression of HER2 was found in 19.6% of the cases and it was associated with high grade tumors with a high mitotic index and phosphorylation of AKT and mTOR. Muscle-invasive tumors presented both cytoplasmic and nuclear losses of PTEN expression. There was no association between HER/AKT/mTOR pathway activation and CAM expression. Although cadherins were often coexpressed, only p-cadherin immunoreactivity was associated with tumor grade and high proliferative index. Conclusions. HER2 overexpression is found in a respective proportion of urothelial carcinomas. P-cadherin expression is associated with high grade UCs but it is not affected by HER2 overexpression or by activation of HER/AKT/mTOR pathway.

  12. Clinical significance of serum vascular cell adhesion molecule-1 levels in patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Joanna W. Ho; Ronnie T. Poon; Cindy S. Tong; Sheung Tat Fan

    2004-01-01

    AIM: To evaluate the correlation between serum vascular cellular adhesion molecule-1 (VCAM-1) levels and clinicopathological features in patients with hepatocellular carcinoma (HCC).METHODS: Ninety-six patients who underwent HCC resection were recruited in the study. Preoperative serum levels of soluble VCAM-1 were measured by enzyme-linked immunosorbent assay.RESULTS: Serum VCAM-1 level in HCC patients was inversely correlated with platelet count (r=-0.431, P<0.001)and serum albumin level (r=-0.279, P<0.001), and positively correlated with serum bilirubin level (r=0.379, P<0.001).Serum VCAM-1 level was not associated with tumor characteristics such as tumor size, venous invasion,presence of microsatellite nodules, tumor grade and tumor stage. Serum VCAM-1 level was significantly higher in HCC patients with cirrhosis compared with those without cirrhosis (median 704 vs 546 ng/mL, P<0.001). Furthermore, a significantly better disease-free survival was observed in HCC patients with low VCAM-1 level (P=0.019).CONCLUSION: Serum VCAM-1 level appears to reflect the severity of underlying chronic liver disease rather than the tumor status in HCC patients, and low preoperative serum VCAM-1 level is predictive of better disease-free survival after surgery.

  13. Identification, isolation, and partial characterization of a novel Streptococcus uberis adhesion molecule (SUAM).

    Science.gov (United States)

    Almeida, Raul A; Luther, Douglas A; Park, Hee-Myung; Oliver, Stephen P

    2006-06-15

    The ability to attach to the host cell surface has been considered an important virulence strategy in many bovine mammary gland pathogens, including Streptococcus uberis. Research conducted in our laboratory lead to the identification of an S. uberis adhesion molecule (SUAM) with affinity for bovine lactoferrin (LF) and delineation of its role in adherence of S. uberis to bovine mammary epithelial cells. Using a selected bacterial surface protein extraction protocol and affinity chromatography, a 112-kDa protein that had a similar molecular mass and the LF affinity as one of the identified S. uberis LBP described by Fang and Oliver in 1999 was found. To further characterize SUAM, the N-terminal amino acid sequence of this protein was elucidated. A protein query versus translated database TBLASTN search of the National Center for Biotechnology (NCBI), non-redundant database, nr, with the LBP N-terminal amino acid sequence showed no significant similarity with previous entries. Antibodies directed against SUAM and a 17 amino acid long N-terminal sequence (pep-SUAM) inhibited adherence to and internalization of S. uberis UT888 into bovine mammary epithelial cells. Data presented suggests that we have discovered a novel bacterial protein involved in the pathogenesis of this economically important mastitis pathogen.

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

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    Harvest F Gu

    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.

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

    Science.gov (United States)

    Smedbakken, Linda; Jensen, Jesper K; Hallén, Jonas; Atar, Dan; Januzzi, James L; Halvorsen, Bente; Aukrust, Pål; Ueland, Thor

    2011-09-01

    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 are associated with long-term mortality after ischemic stroke. In 244 patients with acute ischemic stroke (age 69±13 years), samples of ALCAM were obtained serially from presentation to Day 5 and after 6 months. Patients with overt ischemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months with all-cause and cardiovascular mortality as end points. At follow-up, 72 patients (29%) had died, 43 due to cardiovascular causes. Patients with ALCAM in the fourth quartile (>46.8 ng/mL) at admission had a significantly poorer survival rate on univariate analysis (Pstroke severity, C-reactive protein levels, troponin T levels, and heart and/or renal failure, ALCAM levels above the fourth quartile remained an independent predictor of long-term mortality (adjusted hazard ratio, 2.05; 95% CI, 1.11 to 3.76; P=0.021) and cardiovascular mortality (adjusted hazard ratio, 2.54; 95% CI, 1.06 to 6.07; P=0.028). ALCAM levels measured at admission of acute ischemic stroke are associated with long-term mortality.

  16. Distribution of the feline calicivirus receptor junctional adhesion molecule a in feline tissues.

    Science.gov (United States)

    Pesavento, P A; Stokol, T; Liu, H; van der List, D A; Gaffney, P M; Parker, J S

    2011-03-01

    Junctional adhesion molecule A (JAM-A) is an immunoglobulin superfamily protein that plays an important role in the assembly and maintenance of tight junctions and the establishment of epithelial cell polarity. The feline JAM-A (fJAM-A) is a functional receptor for feline calicivirus (FCV). Among natural diseases associated with FCV infection, isolates that cause oral vesicular disease are detected in epithelial cells; however, isolates that cause systemic disease are detected in multiple cell types. The distribution of an FCV receptor or receptors in feline tissues is relevant to viral pathogenesis in that it should reflect the wide latitude of clinical sequelae associated with FCV infection. The authors examined the expression of feline JAM-A in the cat by using confocal immunofluorescence localization on normal tissues, with special regard to tissue targets of naturally occurring FCV. As described in the human and the mouse, fJAM-A was widely distributed in feline tissues, where it localized at cell-cell junctions of epithelial and endothelial cells. fJAM-A was highly expressed on feline platelets, with lower levels of expression on feline peripheral blood leukocytes. Additionally, FCV infection of a feline epithelial cell monolayer causes redistribution of fJAM-A to the cytosol of infected cells. It is reasonable to propose that the spectrum of lesions caused by FCV reflects disruption of intercellular junctions that rely on fJAM-A function and tight junctional integrity.

  17. Anti-atherosclerotic function of Astragali Radix extract: downregulation of adhesion molecules in vitro and in vivo

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    You Yang

    2012-04-01

    Full Text Available Abstract Background Atherosclerosis is considered to be a chronic inflammatory disease. Astragali Radix extract (ARE is one of the major active ingredients extracted from the root of Astragalus membranaceus Bge. Although ARE has an anti-inflammatory function, its anti-atherosclerotic effects and mechanisms have not yet been elucidated. Methods Murine endothelial SVEC4-10 cells were pretreated with different doses of ARE at different times prior to induction with tumor necrosis factor (TNF-α. Cell adhesion assays were performed using THP-1 cells and assessed by enzyme-linked immunosorbent assay, western blotting and immunofluorescence analyses to detect the expression of vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1, phosphorylated inhibitor of κB (p-iκB and nuclear factor (NF-κB. We also examined the effect of ARE on atherosclerosis in the aortic endothelium of apolipoprotein E-deficient (apoE−/− mice. Results TNF-α strongly increased the expression of VCAM-1 and ICAM-1 accompanied by increased expression of p-iκB and NF-κB proteins. However, the expression levels of VCAM-1 and ICAM-1 were reduced by ARE in dose- and time-dependent manners, with the strongest effect at a dose of 120 μg/ml incubated for 4 h. This was accompanied by significantly decreased expression of p-iκB and inhibited activation of NF-κB. Immunofluorescence analysis also revealed that oral administration of ARE resulted in downregulation of adhesion molecules and decreased expression of macrophages in the aortic endothelium of apoE−/− mice. ARE could suppress the inflammatory reaction and inhibit the progression of atherosclerotic lesions in apoE−/− mice. Conclusion This study demonstrated that ARE might be an effective anti-inflammatory agent for the treatment of atherosclerosis, possibly acting via the decreased expression of adhesion molecules.

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

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    Hala El-Mesallamy

    2007-01-01

    Full Text Available 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 CABG. HbA1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1, and VCAM-1 levels were significantly higher in the diabetic groups than in either healthy controls or IHD subjects. In the diabetic groups, there was a negative association among hsCRP and HDL-C. ET-1, ICAM-1 levels and TAG were positively correlated, as do the association between P-selectin, VCAM-1 and HbA1c%. Also a positive relation was found among hsCRP levels and ICAM-1, as well as MDA and ET-1. P-selectin and ICAM-1 were significantly positively correlated. This study indicates that increased level of oxidative stress marker, proinflammatory markers and their downstream effectors adhesion molecules occurs in type 2 DM.

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

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    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

  20. Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules.

    Science.gov (United States)

    Choi, Hyunsung; Chang, Hyun Joon; Lee, Myeongsang; Na, Sungsoo

    2017-02-04

    In biological systems, structural confinements of amyloid fibrils can be mediated by the role of water molecules. However, the underlying effect of the dynamic behavior of water molecules on structural stabilities of amyloid fibrils is still unclear. By performing molecular dynamics simulations, we investigate the dynamic features and the effect of interior water molecules on conformations and mechanical characteristics of various amyloid fibrils. We find that a specific mechanism induced by the dynamic properties of interior water molecules can affect diffusion of water molecules inside amyloid fibrils, inducing their different structural stabilities. The conformation of amyloid fibrils induced by interior water molecules show the fibrils' different mechanical features. We elucidate the role of confined and movable interior water molecules in structural stabilities of various amyloid fibrils. Our results offer insights not only in further understanding of mechanical features of amyloids as mediated by water molecules, but also in the fine-tuning of the functional abilities of amyloid fibrils for applications.

  1. Stabilization of membrane necks by adhesive particles, substrate surfaces, and constriction forces.

    Science.gov (United States)

    Agudo-Canalejo, Jaime; Lipowsky, Reinhard

    2016-10-21

    Membrane remodelling processes involving the formation and fission of small buds require the formation and closure of narrow membrane necks, both for biological membranes and for model membranes such as lipid bilayers. The conditions required for the stability of such necks are well understood in the context of budding of vesicles with bilayer asymmetry and/or intramembrane domains. In many cases, however, the necks form in the presence of an adhesive surface, such as a solid particle or substrate, or the cellular cortex itself. Examples of such processes in biological cells include endocytosis, exocytosis and phagocytosis of solid particles, the formation of extracellular and outer membrane vesicles by eukaryotic and prokaryotic cells, as well as the closure of the cleavage furrow in cytokinesis. Here, we study the interplay of curvature elasticity, membrane-substrate adhesion, and constriction forces to obtain generalized stability conditions for closed necks which we validate by numerical energy minimization. We then explore the consequences of these stability conditions in several experimentally accessible systems such as particle-filled membrane tubes, supported lipid bilayers, giant plasma membrane vesicles, bacterial outer membrane vesicles, and contractile rings around necks. At the end, we introduce an intrinsic engulfment force that directly describes the interplay between curvature elasticity and membrane-substrate adhesion.

  2. The neural cell adhesion molecule L1 is distinct from the N-CAM related group of surface antigens BSP-2 and D2

    DEFF Research Database (Denmark)

    Faissner, A; Kruse, J; Goridis, C

    1984-01-01

    The neural cell adhesion molecule L1 and the group of N-CAM related molecules, BSP-2 and D2 antigen, are immunochemically distinct molecular species. The two groups of surface molecules are also functionally distinct entities, since inhibition of Ca2+-independent adhesion among early post-natal m......-natal mouse cerebellar cells by Fab fragments of both antibodies are at least additive, when compared with equal concentrations of the individual antibodies....

  3. B-cell receptor-associated protein 31 regulates human embryonic stem cell adhesion, stemness, and survival via control of epithelial cell adhesion molecule.

    Science.gov (United States)

    Kim, Won-Tae; Seo Choi, Hong; Min Lee, Hyun; Jang, Young-Joo; Ryu, Chun Jeih

    2014-10-01

    B-Cell receptor-associated protein 31 (BAP31) regulates the export of secreted membrane proteins from the endoplasmic reticulum (ER) to the downstream secretory pathway. Previously, we generated a monoclonal antibody 297-D4 against the surface molecule on undifferentiated human embryonic stem cells (hESCs). Here, we found that 297-D4 antigen was localized to pluripotent hESCs and downregulated during early differentiation of hESCs and identified that the antigen target of 297-D4 was BAP31 on the hESC-surface. To investigate the functional role of BAP31 in hESCs, BAP31 expression was knocked down by small interfering RNA. BAP31 depletion impaired hESC self-renewal and pluripotency and drove hESC differentiation into multicell lineages. BAP31 depletion hindered hESC proliferation by arresting cell cycle at G0/G1 phase and inducing caspase-independent cell death. Interestingly, BAP31 depletion reduced hESC adhesion to extracellular matrix (ECM). Analysis of cell surface molecules showed decreased expression of epithelial cell adhesion molecule (EpCAM) in BAP31-depleted hESCs, while ectopic expression of BAP31 elevated the expression of EpCAM. EpCAM depletion also reduced hESC adhesion to ECM, arrested cell cycle at G0/G1 phase and induced cell death, producing similar effects to those of BAP31 depletion. BAP31 and EpCAM were physically associated and colocalized at the ER and cell surface. Both BAP31 and EpCAM depletion decreased cyclin D1 and E expression and suppressed PI3K/Akt signaling, suggesting that BAP31 regulates hESC stemness and survival via control of EpCAM expression. These findings provide, for the first time, mechanistic insights into how BAP31 regulates hESC stemness and survival via control of EpCAM expression.

  4. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xia, E-mail: zhongxia1977@126.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B 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-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  5. The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications.

    Science.gov (United States)

    Podar, Klaus; Zimmerhackl, Alexander; Fulciniti, Mariateresa; Tonon, Giovanni; Hainz, Ursula; Tai, Yu-Tzu; Vallet, Sonia; Halama, Niels; Jäger, Dirk; Olson, Dian L; Sattler, Martin; Chauhan, Dharminder; Anderson, Kenneth C

    2011-11-01

    Recent advances regarding the introduction of anti-adhesion strategies as a novel therapeutic concept in oncology hold great promise. Here we evaluated the therapeutic potential of the new-in-class-molecule selective-adhesion-molecule (SAM) inhibitor Natalizumab, a recombinant humanized IgG4 monoclonal antibody, which binds integrin-α4, in multiple myeloma (MM). Natalizumab, but not a control antibody, inhibited adhesion of MM cells to non-cellular and cellular components of the microenvironment as well as disrupted the binding of already adherent MM cells. Consequently, Natalizumab blocked both the proliferative effect of MM-bone marrow (BM) stromal cell interaction on tumour cells, and vascular endothelial growth factor (VEGF)-induced angiogenesis in the BM milieu. Moreover, Natalizumab also blocked VEGF- and insulin-like growth factor 1 (IGF-1)-induced signalling sequelae triggering MM cell migration. In agreement with our in vitro results, Natalizumab inhibited tumour growth, VEGF secretion, and angiogenesis in a human severe combined immunodeficiency murine model of human MM in the human BM microenvironment. Importantly, Natalizumab not only blocked tumour cell adhesion, but also chemosensitized MM cells to bortezomib, in an in vitro therapeutically representative human MM-stroma cell co-culture system model. Our data therefore provide the rationale for the clinical evaluation of Natalizumab, preferably in combination with novel agents (e.g. bortezomib) to enhance MM cytotoxicity and improve patient outcome.

  6. CYTOKINE PROFILE AND ADHESION MOLECULES IN THE PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE COMBINED WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    T. G. Shapovalova

    2010-01-01

    Full Text Available The study involved 56 patients with chronic obstructive pulmonary disease (COPD, stage III-IV, 38 patients with severe bronchial asthma (BA, and 45 patients with a combination of COPD stage III-IV and bronchial asthma at exacerbation period. In all the patients, we have measured blood levels of pro-inflammatory (IL-6, IL -8, TNFα and anti-inflammatory (IL-4 cytokines, amounts of cell adhesion molecules (ICAM- 1, VCAM-1, along with assessment of contractile myocardial functional disorders by means of Doppler echocardiography. Highest rates of pro-inflammatory cytokines and adhesion molecules were found in the group of patients with combined pathology, along with most significant signs of myocardial hypertrophy, both in right and left heart compartments, accompanied by a decrease in contractile myocardial function.

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

    Science.gov (United States)

    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.

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

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    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.

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

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    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

  10. Dehydroepiandrosterone (DHEA) inhibition of monocyte binding by vascular endothelium is associated with sialylation of neural cell adhesion molecule.

    Science.gov (United States)

    Curatola, Anna-Maria; Huang, Kui; Naftolin, Frederick

    2012-01-01

    Adhesion of monocytes to vascular endothelium is necessary for atheroma formation. This adhesion requires binding of endothelial neural cell adhesion molecule (NCAM) to monocyte NCAM. NCAM:NCAM binding is blocked by sialylation of NCAM (polysialylated NCAM; PSA-NCAM). Since estradiol (E2) and dihydrotestosterone (DHT) induced PSA-NCAM and decreased monocyte adhesion, in consideration of possible clinical applications we tested whether their prohormone dehydroepiandrosterone (DHEA) has similar effects. (1) DHEA was administered to cultured human coronary artery endothelial cells (HCAECs) from men and women. Monocyte binding was assessed using fluorescence-labeled monocytes. (2) HCEACs were incubated with E2, DHT, DHEA alone, or with trilostane, fulvestrant or flutamide. Expression of PSA-NCAM was assessed by immunohistochemistry and Western blotting. Dehydroepiandrosterone inhibited monocyte adhesion to HCAECs by ≥50% (P DHEA's inhibition of monocyte binding appeared to be gender dependent. The DHEA-induced expression of PSA-NCAM was completely blocked by trilostane. In these preliminary in vitro studies, DHEA increased PSA-NCAM expression and inhibited monocyte binding in an estrogen- and androgen receptor-dependent manner. Dehydroepiandrosteroneappears to act via its end metabolites, E2 and DHT. Dehydroepiandrosterone could furnish clinical prevention against atherogenesis and arteriosclerosis.

  11. Neural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling

    Science.gov (United States)

    Demyanenko, Galina P.; Mohan, Vishwa; Zhang, Xuying; Brennaman, Leann H.; Dharbal, Katherine E.S.; Tran, Tracy S.; Manis, Paul B.

    2014-01-01

    Neuron-glial related cell adhesion molecule (NrCAM) is a regulator of axon growth and repellent guidance, and has been implicated in autism spectrum disorders. Here a novel postsynaptic role for NrCAM in Semaphorin3F (Sema3F)-induced dendritic spine remodeling was identified in pyramidal neurons of the primary visual cortex (V1). NrCAM localized to dendritic spines of star pyramidal cells in postnatal V1, where it was coexpressed with Sema3F. NrCAM deletion in mice resulted in elevated spine densities on apical dendrites of star pyramidal cells at both postnatal and adult stages, and electron microscopy revealed increased numbers of asymmetric synapses in layer 4 of V1. Whole-cell recordings in cortical slices from NrCAM-null mice revealed increased frequency of mEPSCs in star pyramidal neurons. Recombinant Sema3F-Fc protein induced spine retraction on apical dendrites of wild-type, but not NrCAM-null cortical neurons in culture, while re-expression of NrCAM rescued the spine retraction response. NrCAM formed a complex in brain with Sema3F receptor subunits Neuropilin-2 (Npn-2) and PlexinA3 (PlexA3) through an Npn-2-binding sequence (TARNER) in the extracellular Ig1 domain. A trans heterozygous genetic interaction test demonstrated that Sema3F and NrCAM pathways interacted in vivo to regulate spine density in star pyramidal neurons. These findings reveal NrCAM as a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the Sema3F receptor complex. The results implicate NrCAM as a contributor to excitatory/inhibitory balance in neocortical circuits. PMID:25143608

  12. Intraocular soluble intracellular adhesion molecule-1 correlates with subretinal fluid height of diabetic macular edema

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    Dan Zhu

    2014-01-01

    Full Text Available Objective: To investigate the correlations between aqueous concentrations of vascular endothelial growth factor (VEGF, monocyte chemoattractant protein-1 (MCP-1, soluble intracellular adhesion molecule-1 (sICAM-1 and diabetic macular edema (DME. Materials and Methods: VEGF, MCP-1 and sICAM-1 concentrations in aqueous humor samples of 22 patients with DME and 23 patients with cataract of a control group were measured with solid-phase chemiluminescence immunoassay. Results: Aqueous VEGF (89.2 ± 58.5 pg/ml versus 48.5 ± 27.8 pg/ml, P = 0.006, MCP-1 (684.2 ± 423.4 pg/ml versus 432.4 ± 230.4 pg/ml, P = 0.019 and sICAM-1 (3213.8 ± 2581.6 pg/ml versus 260.2 ± 212.2 pg/ml, P < 0.001 all vary significantly between DME group and control group. Maximum height of submacular fluid measured by Optical coherence tomography (OCT was significantly associated with aqueous sICAM-1 (r = -0.45, P = 0.034. The maximum height of macular thickness measured by OCT was not significantly associated with either VEGF (P = 0.300, MCP-1 (P = 0.320 or sICAM-1 (P = 0.285. Conclusions: Our results suggest that sICAM-1 may majorly contribute to the formation of subretinal fluid in DME patients and imply that MCP-1 and sICAM-1 may be the potential therapy targets, besides VEGF.

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

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    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.

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

    OpenAIRE

    Dilip Kumar Swain; Mohar Singh Kushwah; Ajay Kumar Dang

    2016-01-01

    Objective: The present study was an attempt to delineate the roles played by the neutrophil surface adhesion molecules and toll like receptors (TLRs) in crossbred cows suffering from Staphylococcus aureus subclinical and clinical mastitis. Materials and methods: Thirty six Karan Fries (KF) cows were categorized into three groups namely healthy (n=12), subclinical mastitis (SCM; n=12) and clinical mastitis (CM; n=12) after screening 146 cows. The grouping was done based on evaluation of co...

  15. Serum inflammatory cytokine and adhesion molecule content in patients with coronary heart disease and their value for disease severity diagnosis

    Institute of Scientific and Technical Information of China (English)

    Wei Hu; Li-juan Fu; Jiang-Qiao Hu; Peng Liang; Lin Pi; Gui-Hua Li

    2016-01-01

    Objective:To detect inflammatory cytokine and adhesion molecule content in patients with coronary heart disease and analyze their value for disease severity diagnosis.Methods:A total of 113 patients with coronary heart disease and 107 healthy subjects were included in the study and further divided into mild group (n=40), moderate group (n=52) and severe group (n=21) according to the severity of coronary heart disease. Serum inflammatory cytokine and adhesion molecule content of all subjects were detected, and the value of inflammatory cytokine and adhesion molecule content for judging the severity of coronary heart disease was further analyzed.Results:Serum CRP, TNF-α and YKL-40 levels of coronary heart disease group were higher than those of healthy control group while IL-35 level was lower than that of healthy control group (P<0.05); serum E-selectin, ICAM-1, VCAM-1 and sICAM-1 levels of coronary heart disease group were higher than those of healthy control group (P<0.05); serum CRP, TNF-α, YKL-40, E-selectin, ICAM-1, VCAM-1 and sICAM-1 levels of mild group were lower than those of moderate group and severe group, IL-35 level was higher than those of moderate group and severe group (P<0.05), and with the aggravation of coronary heart disease, CRP, TNF-α, YKL-40, E-selectin, ICAM-1, VCAM-1 and sICAM-1 levels increased while IL-35 level decreased (P<0.05).Conclusions: Serum inflammatory cytokine and adhesion molecule content change significantly in patients with coronary heart disease, are directly correlated with the severity of coronary heart disease and can be used as the reliable means to assess the condition and prognosis of patients with coronary heart disease.

  16. Glutamine Supplementation Attenuates Expressions of Adhesion Molecules and Chemokine Receptors on T Cells in a Murine Model of Acute Colitis

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    Yu-Chen Hou

    2014-01-01

    Full Text Available Background. Migration of T cells into the colon plays a major role in the pathogenesis in inflammatory bowel disease. This study investigated the effects of glutamine (Gln supplementation on chemokine receptors and adhesion molecules expressed by T cells in mice with dextran sulfate sodium- (DSS- induced colitis. Methods. C57BL/6 mice were fed either a standard diet or a Gln diet replacing 25% of the total nitrogen. After being fed the diets for 5 days, half of the mice from both groups were given 1.5% DSS in drinking water to induce colitis. Mice were killed after 5 days of DSS exposure. Results. DSS colitis resulted in higher expression levels of P-selectin glycoprotein ligand- (PSGL- 1, leukocyte function-associated antigen- (LFA- 1, and C-C chemokine receptor type 9 (CCR9 by T helper (Th and cytotoxic T (Tc cells, and mRNA levels of endothelial adhesion molecules in colons were upregulated. Gln supplementation decreased expressions of PSGL-1, LFA-1, and CCR9 by Th cells. Colonic gene expressions of endothelial adhesion molecules were also lower in Gln-colitis mice. Histological finding showed that colon infiltrating Th cells were less in the DSS group with Gln administration. Conclusions. Gln supplementation may ameliorate the inflammation of colitis possibly via suppression of T cell migration.

  17. SC1, an immunoglobulin-superfamily cell adhesion molecule, is involved in the brain metastatic activity of lung cancer cells

    Science.gov (United States)

    KUBOTA, YUKA; KIRIMURA, NAOKI; SHIBA, HATSUKI; ADACHI, KAZUHIDE; TSUKAMOTO, YASUHIRO

    2015-01-01

    SC1 is a cell adhesion molecule that belongs to the immunoglobulin superfamily; this molecule was initially purified from the chick embryonic nervous system and was reported to exhibit homophilic adhesion activity. SC1 is transiently expressed in various organs during development and has been identified in numerous neoplastic tissues, including lung cancer and colorectal carcinomas. The present study focused on the encephalic metastasis of lung cancer cells with respect to the potential function of SC1, as this molecule is known to be consistently expressed in the central nervous system as well as lung cancers. SC1 complementary DNA was introduced into A549 cells, a human lung cancer-derived cell line. The stable overexpression of the SC1 protein in A549 cells was demonstrated to enhance the self-aggregation of the cells. In addition, the SC1 transfectants enhanced the metastatic and invasive potential to the encephalic parenchyma following implantation into nude mice. In conclusion, the results of the present study demonstrated that cell adhesion due interactions between SC1 on brain tissue and SC1 on lung cancer cells was involved in the malignant aspects of lung cancer, including invasion and metastasis to the brain. PMID:26622821

  18. Intercellular adhesion molecule-1 expression in the hippocampal CA1 region of hyperlipidemic rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yingying Cheng; Ying Zhang; Hongmei Song; Jiachun Feng

    2012-01-01

    Chronic cerebral ischemia is a pathological process in many cerebrovascular diseases and it is induced by long-term hyperlipidemia, hypertension and diabetes mellitus. After being fed a high-fat diet for 4 weeks, rats were subjected to permanent occlusion of bilateral common carotid arteries to establish rat models of chronic cerebral ischemia with hyperlipidemia. Intercellular adhesion molecule-1 expression in rat hippocampal CA1 region was determined to better understand the mechanism underlying the effects of hyperlipidemia on chronic cerebral ischemia. Water maze test results showed that the cognitive function of rats with hyperlipidemia or chronic cerebral ischemia, particularly in rats with hyperlipidemia combined with chronic cerebral ischemia, gradually decreased between 1 and 4 months after occlusion of the bilateral common carotid arteries. This correlated with pathological changes in the hippocampal CA1 region as detected by hematoxylin-eosin staining. Immunohistochemical staining showed that intercellular adhesion molecule-1 expression in the hippocampal CA1 region was noticeably increased in rats with hyperlipidemia or chronic cerebral ischemia, in particular in rats with hyperlipidemia combined with chronic cerebral ischemia. These findings suggest that hyperlipidemia aggravates chronic cerebral ischemia-induced neurological damage and cognitive impairment in the rat hippocampal CA1 region, which may be mediated, at least in part, by up-regulated expression of intercellular adhesion molecule-1.

  19. Babesia bovis: expression of adhesion molecules in bovine umbilical endothelial cells stimulated with plasma from infected cattle

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    Marlene I. Vargas

    2014-10-01

    Full Text Available Ten male, 12-month-old Jersey with intact spleens, serologically and parasitologically free from Babesia were housed individually in an arthropod-free isolation system from birth and throughout entire experiment. The animals were randomly divided into two groups. Five animals (group A were intravenously inoculated with 6.6 X10(7 red blood cells parasitized with pathogenic sample of Babesia bovis (passage 7 BboUFV-1, for the subsequent "ex vivo" determination of the expression of adhesion molecules. Five non-inoculated animals (group B were used as the negative control. The expression of the adhesion molecules ICAM-1, VCAM, PECAM-1 E-selectin and thrombospondin (TSP was measured in bovine umbilical vein endothelial cells (BUVECs. The endothelial cells stimulated with a pool of plasma from animals infected with the BboUFV-1 7th passage sample had a much more intense immunostaining of ICAM-1, VCAM, PECAM-1 E-selectin and TSP, compared to the cells which did not received the stimulus. The results suggest that proinflammatory cytokines released in the acute phase of babesiosis may be involved in the expression of adhesion molecules thereby implicating them in the pathophysiology of babesiosis caused by B. bovis.

  20. The limited immunomodulatory effects of escharectomy on the kinetics of endotoxin, cytokines, and adhesion molecules in major burns

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    Tae-Hyung Han

    2004-01-01

    Full Text Available ESCHARECTOMY has been shown to improve the survival rates and the outcomes in burns. This observational study was conducted to assess the role of escharectomy on the inflammatory mediators in major burns. Seventeen ASA physical status II or status III adult surviving major burn patients were recruited. When the escharectomy was scheduled, a series of blood samples was obtained at −3 and −1 days preoperation, and +1 and +3 postoperation. The changing levels of endotoxin, cytokines, and adhesion molecules were measured with a quantitative sandwich immunoassay. Extensive escharectomy did not appear to have any significant impact on the levels of tumor necrosis factor alpha, interleukin-10, soluble intracellular adhesion molecule-1 and soluble vascular adhesion molecule-1. Meanwhile, endotoxin and E-selectin were significantly decreased after escharectomy. Escharectomy appeared to have a limited immunomodulatory effect on the inflammatory mediators in systemic inflammatory responses induced by major burns. This is probably related to the timing and extent of surgery, and the complex nature of burn-related inflammation.

  1. Tie2 Signaling Enhances Mast Cell Progenitor Adhesion to Vascular Cell Adhesion Molecule-1 (VCAM-1 through α4β1 Integrin.

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    Kazumasa Kanemaru

    Full Text Available Mast cell (MC activation contributes considerably to immune responses, such as host protection and allergy. Cell surface immunoreceptors expressed on MCs play an important role in MC activation. Although various immunoreceptors on MCs have been identified, the regulatory mechanism of MC activation is not fully understood. To understand the regulatory mechanisms of MC activation, we used gene expression analyses of human and mouse MCs to identify a novel immunoreceptor expressed on MCs. We found that Tek, which encodes Tie2, was preferentially expressed in the MCs of both humans and mice. However, Tie2 was not detected on the cell surface of the mouse MCs of the peritoneal cavity, ear skin, or colon lamina propria. In contrast, it was expressed on mouse bone marrow-derived MCs and bone marrow MC progenitors (BM-MCps. Stimulation of Tie2 by its ligand angiopoietin-1 induced tyrosine phosphorylation of Tie2 in MEDMC-BRC6, a mouse embryonic stem cell-derived mast cell line, and enhanced MEDMC-BRC6 and mouse BM-MCp adhesion to vascular cell adhesion molecule-1 (VCAM-1 through α4β1 integrin. These results suggest that Tie2 signaling induces α4β1 integrin activation on BM-MCps for adhesion to VCAM-1.

  2. Conditional stability of diatomic molecule driven by a weak laser field

    Institute of Scientific and Technical Information of China (English)

    Chong Gui-Shu; Hai Wen-Hua; Xie Qiong-Tao

    2005-01-01

    Using a direct perturbation method, we investigate the stability of a diatomic molecule modelled by a weakly laser-driven Morse oscillator. It is shown that stationary state solution of the system is stable in the sense of Lyapunov and the periodical one possesses conditional stability, namely its stability depends on the initial conditions and system parameters. The corresponding sufficient and necessary conditions are established that indicate the stable states associated with some discrete energies. The results reveal how a diatomic molecule can be stabilized or dissociated with a weak laser, and demonstrate that the mathematical conditional stability works in the considered physical system.

  3. Differential modulation of IL-1-induced endothelial adhesion molecules and transendothelial migration of granulocytes by G-CSF.

    Science.gov (United States)

    Eissner, G; Lindner, H; Reisbach, G; Klauke, I; Holler, E

    1997-06-01

    Granulocyte colony stimulating factor (G-CSF) is widely used for mobilization of haemopoietic stem cells into the peripheral blood. However, little is known about the mechanisms involved in mobilization and the immune modulatory effects of this growth factor. In this report we show that G-CSF down-regulated intercellular adhesion molecule 1 (ICAM-1) induced by Interleukin-1 (IL-1) on human endothelial cells. Interestingly, the G-CSF-mediated down-modulation of IL-1-induced ICAM-1 appeared to be biphasic. In pharmacological concentrations (> 300 ng/ml), and in dose ranges of plasma G-CSF levels above that of nonfebrile healthy individuals (30 pg/ml), a significant decrease in surface ICAM-1 could be observed. This could be explained, at least in part, by an increased autocrine G-CSF production by endothelial cells in response to IL-1 and exogenous G-CSF. In contrast to ICAM-1, IL-1-triggered VCAM-1 expression was superinduced by G-CSF with the optimal concentration of 30 pg/ml. To evaluate the functional significance of these findings, 51Cr adhesion assays with peripheral blood mononuclear cells (PBMC) or granulocytes known to lack the VCAM-1 counter-receptor very late antigen 4 (VLA-4) and IL-1-stimulated endothelial cells, in the presence or absence of G-CSF, were performed. G-CSF could not inhibit the IL-1-induced adhesion of PBMC to endothelial cells, which may be due to the differential adhesion molecule modulation. In contrast, granulocyte adhesion induced by IL-1 could effectively be blocked by co-incubation with G-CSF. Finally, G-CSF also inhibited transendothelial migration of granulocytes through IL-1-activated endothelial cells in a concentration-dependent manner.

  4. Expression pattern of epithelial cell adhesion molecule on normal and malignant colon tissues

    Institute of Scientific and Technical Information of China (English)

    Xin Xie; Chun-Yan Wang; Yun-Xin Cao; Wei Wang; Ran Zhuang; Li-Hua Chen; Na-Na Dang; Liang Fang; Bo-Quan Jin

    2005-01-01

    AIM: To investigate the expression pattern of epithelial cell adhesion molecule (Ep-CAM) on normal and malignant colon tissues to evaluate its diagnostic and therapeutic significance.METHODS: cDNA encoding Ep-CAv extracellular domain was cloned by reverse transcription-polymerase chain reaction (RT-PCR) from excised malignant colon tissues and inserted into a glutathione S-transferase (GST)-tagged vector. EpCAM-GST fusion protein was induced by isopropyl-β-D-thiogalactopyranoside (IPTG) and purified with glutathionesepharose. The Ep-CAM-GST fusion protein was mixed with Freund's adjuvant and Balb/c mice were immunized with it. Sp2/0 myeloma cells were fused with the spleen cells of the immunized mice. After having selected by indirect ELISA, the anti-Ep-CAM monoclonal antibodies (NAbs) were generated and the corresponding ascites were obtained.Finally, the human colon carcinoma tissue array prepared from seventy individual patients was stained with the antiEp-CAM NAbs.RESULTS: The isolated Ep-CAM cDNA sequence was identical to the data in GenBank. The expressed fusion protein was almost soluble and had a molecular weight (NW) of 53 ku.Four NAbs against Ep-CAM were obtained and designated as FMU-Ep1, FMU-Ep2, FMU-Ep3 and FMU-Ep4 respectively.Among them, FMU-Ep4 could recognize the natural EpCAM on Colo205 and SW480 cells, and all of them could be used for immunohistochemical staining of tissue sections.It was found that Ep-CAM was distributed differently in normal and various malignant colon tissues, including squamous cell carcinoma, signet-ring cell carcinoma and adenocarcinoma.In normal colon gland epithelia, Ep-CAM antigen was mainly distributed on the basolateral membrane and in the region between the basolateral membrane and the cytoplastic part near the nuclei, whereas the expression pattern of colon malignancies was mainly on the whole surface of epithelia and the expression was much higher than the normal colon tissues. The staining pattern of tissue array

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

    DEFF Research Database (Denmark)

    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...

  6. Simple surface engineering of polydimethylsiloxane with polydopamine for stabilized mesenchymal stem cell adhesion and multipotency

    Science.gov (United States)

    Chuah, Yon Jin; Koh, Yi Ting; Lim, Kaiyang; Menon, Nishanth V.; Wu, Yingnan; Kang, Yuejun

    2015-01-01

    Polydimethylsiloxane (PDMS) has been extensively exploited to study stem cell physiology in the field of mechanobiology and microfluidic chips due to their transparency, low cost and ease of fabrication. However, its intrinsic high hydrophobicity renders a surface incompatible for prolonged cell adhesion and proliferation. Plasma-treated or protein-coated PDMS shows some improvement but these strategies are often short-lived with either cell aggregates formation or cell sheet dissociation. Recently, chemical functionalization of PDMS surfaces has proved to be able to stabilize long-term culture but the chemicals and procedures involved are not user- and eco-friendly. Herein, we aim to tailor greener and biocompatible PDMS surfaces by developing a one-step bio-inspired polydopamine coating strategy to stabilize long-term bone marrow stromal cell culture on PDMS substrates. Characterization of the polydopamine-coated PDMS surfaces has revealed changes in surface wettability and presence of hydroxyl and secondary amines as compared to uncoated surfaces. These changes in PDMS surface profile contribute to the stability in BMSCs adhesion, proliferation and multipotency. This simple methodology can significantly enhance the biocompatibility of PDMS-based microfluidic devices for long-term cell analysis or mechanobiological studies. PMID:26647719

  7. Cytotoxicity, oxidative stress and expression of adhesion molecules in human umbilical vein endothelial cells exposed to dust from paints with or without nanoparticles

    DEFF Research Database (Denmark)

    Mikkelsen, Lone; Jensen, Keld A; Koponen, Ismo K

    2013-01-01

    Abstract Nanoparticles in primary form and nanoproducts might elicit different toxicological responses. We compared paint-related nanoparticles with respect to effects on endothelial oxidative stress, cytotoxicity and cell adhesion molecule expression. Primary human umbilical vein endothelial cel...

  8. Degradation of adhesion molecules of G361 melanoma cells by a non-thermal atmospheric pressure microplasma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H J [Department of Electrical Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Shon, C H [Korea Electrotechnology Research Institute, Changwon 641-120 (Korea, Republic of); Kim, Y S; Kim, S [Department of Pediatric Dentistry, Pusan National University, Busan 602-739 (Korea, Republic of); Kim, G C [Department of Oral Anatomy, Pusan National University, Busan 602-739 (Korea, Republic of); Kong, M G [Department of Electronics and Electrical Engineering, Loughborough University, Leics LE11 3TU (United Kingdom)], E-mail: ki9100m@pusan.ac.kr, E-mail: m.g.kong@lboro.ac.uk

    2009-11-15

    Increased expression of integrins and focal adhesion kinase (FAK) is important for the survival, growth and metastasis of melanoma cells. Based on this well-established observation in oncology, we propose to use degradation of integrin and FAK proteins as a potential strategy for melanoma cancer therapy. A low-temperature radio-frequency atmospheric microplasma jet is used to study their effects on the adhesion molecules of G361 melanoma cells. Microplasma treatment is shown to (1) cause significant cell detachment from the bottom of microtiter plates coated with collagen, (2) induce the death of human melanoma cells, (3) inhibit the expression of integrin {alpha}{sub 2}, integrin {alpha}{sub 4} and FAK on the cell surface and finally (4) change well-stretched actin filaments to a diffuse pattern. These results suggest that cold atmospheric pressure plasmas can strongly inhibit the adhesion of melanoma cells by reducing the activities of adhesion proteins such as integrins and FAK, key biomolecules that are known to be important in malignant transformation and acquisition of metastatic phenotypes.

  9. Degradation of adhesion molecules of G361 melanoma cells by a non-thermal atmospheric pressure microplasma

    Science.gov (United States)

    Lee, H. J.; Shon, C. H.; Kim, Y. S.; Kim, S.; Kim, G. C.; Kong, M. G.

    2009-11-01

    Increased expression of integrins and focal adhesion kinase (FAK) is important for the survival, growth and metastasis of melanoma cells. Based on this well-established observation in oncology, we propose to use degradation of integrin and FAK proteins as a potential strategy for melanoma cancer therapy. A low-temperature radio-frequency atmospheric microplasma jet is used to study their effects on the adhesion molecules of G361 melanoma cells. Microplasma treatment is shown to (1) cause significant cell detachment from the bottom of microtiter plates coated with collagen, (2) induce the death of human melanoma cells, (3) inhibit the expression of integrin α2, integrin α4 and FAK on the cell surface and finally (4) change well-stretched actin filaments to a diffuse pattern. These results suggest that cold atmospheric pressure plasmas can strongly inhibit the adhesion of melanoma cells by reducing the activities of adhesion proteins such as integrins and FAK, key biomolecules that are known to be important in malignant transformation and acquisition of metastatic phenotypes.

  10. Targeted Gene Deletion Demonstrates that Cell Adhesion MoleculeICAM-4 is Critical for Erythroblastic Island Formation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gloria; Lo, Annie; Short, Sarah A.; Mankelow, Tosti J.; Spring, Frances; Parsons, Stephen F.; Mohandas, Narla; Anstee, David J.; Chasis, Joel Anne

    2006-02-15

    Erythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule-4 (ICAM-4), animmunoglobulin superfamily member, participates in island formation. Earlier, we identified alpha V integrins as ICAM-4 counter receptors. Since macrophages express alpha V, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knockout mice and developed quantitative, live cell techniques for harvesting intact islands and for reforming islands in vitro. We observed a 47 percent decrease in islands reconstituted from ICAM-4 null marrow compared to wild type. We also found a striking decrease in islands formed in vivo in knockout mice. Further, peptides that block ICAM-4 alpha V adhesion produced a 53-57 percent decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage alpha V functions in island integrity. Importantly, we documented that alpha V integrin is expressed in macrophages isolated from erythro blastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/alpha V adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis.

  11. Ligation of MHC class I and class II molecules can lead to heterologous desensitization of signal transduction pathways that regulate homotypic adhesion in human lymphocytes.

    Science.gov (United States)

    Wagner, N; Engel, P; Vega, M; Tedder, T F

    1994-06-01

    Engagement of lymphocyte MHC class I and class II Ags activates an array of intracellular signal transduction pathways that up-regulates the activity of cell-surface adhesion receptors, resulting in homotypic cell-cell aggregation. In this study, engagement of MHC class I and class II molecules with specific mAbs was shown to also inhibit lymphocyte homotypic adhesion. Two mAbs reactive with class II Ag, homotypic adhesion blocking mAb (HAB)-2, and HAB-3, and one mAb reactive with class I Ag, HAB-4, were generated that inhibited homotypic adhesion of activated lymphocytes and B and T cell lines at concentrations as low as 0.1 microgram/ml. Binding of these mAbs resulted in heterologous desensitization of other surface signal transduction molecules as homotypic adhesion induced through class I, class II, CD19, CD20, CD39, CD40, Leu-13, and PMA was also inhibited. The spontaneous adhesion exhibited by some cell lines was also abrogated by binding of these mAbs. Abs that either induced, blocked, or had no effect on adhesion bound to distinct epitopes on class I, whereas the anti-class II mAbs recognized either distinct or overlapping epitopes. Thus, engagement of distinct epitopes on MHC molecules can result in homologous or heterologous desensitization of cell-surface signaling molecules. The induction or inhibition of homotypic adhesion through class I molecules did not require the presence of the cytoplasmic domain, as deletion of this portion of the class I molecule had no effect. In contrast, the transmembrane region was essential for signal transduction as the mAbs binding to a chimeric molecule in which the transmembrane and cytoplasmic domains of class I were exchanged with those of the HB15 molecule did not induce or inhibit homotypic adhesion. Although this report is the first demonstration that homotypic adhesion can be influenced in a negative manner through MHC molecules, these findings demonstrate a considerable level of cross-talk between MHC molecules

  12. Role Of Adhesion Molecules Vcam-1 And Ve-Cadherin In Endothelium Dysfunction Development At Hemorrhagic Fever With Renal Syndrome

    Directory of Open Access Journals (Sweden)

    А.А. Baygildina

    2009-12-01

    Full Text Available The research goal is to determine the changes in concentration of both sVCAM-1 and VE-cadherin in blood serum of patients suffered from hemorrhagic fever with renal syndrome (HFRS. 87 patients aged 15-65 were examined. Concentrations of both sVCAM-1 and VE- cadherin in blood serum by means of "Bender MedSystems" (Austria ELISA test were determined. It was shown that in both medium severe and severe forms of HFRS statistically the significant rise of sVCAM-1 concentration in blood with high indices in oliguric period took place. Complicated form was characterized by high indices of sVCAM-1 level in fever period, extremely decreasing in concentration in oliguric period and tendency to normalizing in clinical convalescence period. VE-cadherin level in blood was predominantly lower than control in all the observed groups with the exception of fever period in group with medium severe disease form. Negative correlation of normal intensity between adhesion molecules levels in blood was revealed. In conclusion it is necessary to point out that high VCAM-1 expression by endotheliocytes evidences the development of an adhesion form of endothelial dysfunction, low VE-cadherin production in a base for development of angiogenic form of endothelial dysfunction and changes in expression of these adhesion molecules that have adaptive metabolic response to macroorganism of HFRS pathogenic action

  13. The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo

    Directory of Open Access Journals (Sweden)

    Martin Veronica

    2008-04-01

    Full Text Available Abstract Background Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth. Results We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth. Conclusion We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the

  14. Biosynthesis of the D2 cell adhesion molecule: pulse-chase studies in cultured fetal rat neuronal cells

    DEFF Research Database (Denmark)

    Lyles, J M; Norrild, B; Bock, E

    1984-01-01

    D2 is a membrane glycoprotein that is believed to function as a cell adhesion molecule (CAM) in neural cells. We have examined its biosynthesis in cultured fetal rat brain neurones. We found D2-CAM to be synthesized initially as two polypeptides: Mr 186,000 (A) and Mr 136,000 (B). With increasing...... chase times the Mr of both molecules increased to 187,000-201,000 (A) and 137,000-158,000 (B). These were similar to the sizes of D2-CAM labeled with [14C]glucosamine, [3H]fucose and [14C]mannosamine, indicating that the higher Mr species are glycoproteins. In the presence of tunicamycin, which...... pulse or chase times, showing that these molecules are not interconverted. Thus, our data indicate that the neuronal D2-CAM glycoproteins are derived from two mRNAs....

  15. Stabilization of Ultracold Molecules Using Optimal Control Theory

    CERN Document Server

    Koch, C P; Kosloff, R; Koch, Christiane P.; Palao, Jos\\'e P.; Kosloff, Ronnie

    2004-01-01

    In recent experiments on ultracold matter, molecules have been produced from ultracold atoms by photoassociation, Feshbach resonances, and three-body recombination. The created molecules are translationally cold, but vibrationally highly excited. This will eventually lead them to be lost from the trap due to collisions. We propose shaped laser pulses to transfer these highly excited molecules to their ground vibrational level. Optimal control theory is employed to find the light field that will carry out this task with minimum intensity. We present results for the sodium dimer. The final target can be reached to within 99% if the initial guess field is physically motivated. We find that the optimal fields contain the transition frequencies required by a good Franck-Condon pumping scheme. The analysis is able to identify the ranges of intensity and pulse duration which are able to achieve this task before other competing process take place. Such a scheme could produce stable ultracold molecular samples or even...

  16. Characterization of adhesive molecule with affinity to Caco-2 cells in Lactobacillus acidophilus by proteome analysis.

    Science.gov (United States)

    Ashida, Nobuhisa; Yanagihara, Sae; Shinoda, Tadashi; Yamamoto, Naoyuki

    2011-10-01

    The adhesive activities of eight Lactobacillus acidophilus strains toward intestinal epithelial Caco-2 cells were studied to understand the probiotic characteristics of the L. acidophilus L-92 strain. Most of the strains, including L-92, showed high adhesive activity; CP23 showed the lowest adhesive activity. CP23 was selected for comparative analysis of cell wall-associated proteins versus the L-92 strain. Cell wall-associated proteins extracted from L-92 and CP23 were subjected to two-dimensional electrophoresis, and major spots observed in the former were compared to the corresponding spots in the latter. To understand the effects of key components of L-92 on its adhesion to Caco-2 cells, 18 spots with stronger signals in L-92 than those in CP23 were identified by a MALDI-TOF/TOF of Ultraflex analysis. Among the identified proteins of L-92, surface-layer protein A (SlpA) was considered strongly involved in adhesion in the eight L. acidophilus strains. To study the importance of SlpA in the adhesion of L. acidophilus, the amounts of SlpA proteins in LiCl extracts of the eight strains were compared by SDSpolyacrylamide gel electrophoresis. As a result, the adhesive abilities of L. acidophilus strains to Caco-2 cells correlated closely to the amount of SlpA in the cells and the productivity of IL-12, an inflammatory cytokine, in all eight strains. These results strongly suggested that SlpA in L. acidophilus might play a key role in its attachment to Caco-2 cells and in the release of IL-12 from dendritic cells.

  17. The influence of propofol on the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in reoxygenated human umbilical vein endothelial cells.

    LENUS (Irish Health Repository)

    Corcoran, T B

    2012-02-03

    BACKGROUND: Leucocytes are a pivotal component of the inflammatory cascade that results in tissue injury in a large group of disorders. Free radical production and endothelial activation promote leucocyte-endothelium interactions via endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) which augment these processes, particularly in the setting of reperfusion injury. Propofol has antioxidant properties which may attenuate the increased expression of these molecules that is observed. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia, then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg mL(-1) or propofol 5 microg mL(-1), for 4 h after reoxygenation and were examined for ICAM-1 and VCAM-1 expression. RESULTS: Hypoxia did not increase the expression of ICAM-1\\/VCAM-1. ICAM-1 expression peaked 12 h after reoxygenation (21.75(0.6) vs. 9.6(1.3), P = 0.02). Propofol, but not Diprivan, prevented this increase (8.2(2.9) vs. 21.75(0.6), P = 0.009). VCAM-1 expression peaked 24 h after reoxygenation (9.8(0.9) vs. 6.6(0.6), P = 0.03). Propofol and Diprivan prevented this increase, with no difference between the two treatments observed (4.3(0.3) and 6.4(0.5) vs. 9.8(0.9), P = 0.001, 0.02, respectively). CONCLUSION: These effects are likely to be attributable to the antioxidant properties of propofol, and suggest that propofol may have a protective role in disorders where free radical mediated injury promotes leucocyte-endothelium adhesive interactions.

  18. The effect of inhaled sodium cromoglycate on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in asthmatics.

    Science.gov (United States)

    Hoshino, M; Nakamura, Y

    1997-04-01

    There is no direct evidence of the anti-inflammatory effect of inhaled sodium cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in patients with asthma, biopsies of the bronchial mucosa were taken from nine patients with atopic bronchial asthma before and after treatment with inhaled SCG (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at the same time as adhesion molecules expressed in vascular endothelium. The intensity of ICAM-1 expression in the bronchial epithelium was also evaluated. The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were significantly reduced as a result of SCG administration, and the expression of ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant correlation was found between ICAM-1 expression and T-lymphocytes and between VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does have an effect on the infiltration of the bronchial mucosa by inflammatory cells and also on the expression of adhesion molecules.

  19. Initial Bacterial Adhesion on Different Yttria-Stabilized Tetragonal Zirconia Implant Surfaces in Vitro

    Directory of Open Access Journals (Sweden)

    Lamprini Karygianni

    2013-12-01

    Full Text Available Bacterial adhesion to implant biomaterials constitutes a virulence factor leading to biofilm formation, infection and treatment failure. The aim of this study was to examine the initial bacterial adhesion on different implant materials in vitro. Four implant biomaterials were incubated with Enterococcus faecalis, Staphylococcus aureus and Candida albicans for 2 h: 3 mol % yttria-stabilized tetragonal zirconia polycrystal surface (B1a, B1a with zirconium oxide (ZrO2 coating (B2a, B1a with zirconia-based composite coating (B1b and B1a with zirconia-based composite and ZrO2 coatings (B2b. Bovine enamel slabs (BES served as control. The adherent microorganisms were quantified and visualized using scanning electron microscopy (SEM; DAPI and live/dead staining. The lowest bacterial count of E. faecalis was detected on BES and the highest on B1a. The fewest vital C. albicans strains (42.22% were detected on B2a surfaces, while most E. faecalis and S. aureus strains (approximately 80% were vital overall. Compared to BES; coated and uncoated zirconia substrata exhibited no anti-adhesive properties. Further improvement of the material surface characteristics is essential.

  20. Initial Bacterial Adhesion on Different Yttria-Stabilized Tetragonal Zirconia Implant Surfaces in Vitro

    Science.gov (United States)

    Karygianni, Lamprini; Jähnig, Andrea; Schienle, Stefanie; Bernsmann, Falk; Adolfsson, Erik; Kohal, Ralf J.; Chevalier, Jérôme; Hellwig, Elmar; Al-Ahmad, Ali

    2013-01-01

    Bacterial adhesion to implant biomaterials constitutes a virulence factor leading to biofilm formation, infection and treatment failure. The aim of this study was to examine the initial bacterial adhesion on different implant materials in vitro. Four implant biomaterials were incubated with Enterococcus faecalis, Staphylococcus aureus and Candida albicans for 2 h: 3 mol % yttria-stabilized tetragonal zirconia polycrystal surface (B1a), B1a with zirconium oxide (ZrO2) coating (B2a), B1a with zirconia-based composite coating (B1b) and B1a with zirconia-based composite and ZrO2 coatings (B2b). Bovine enamel slabs (BES) served as control. The adherent microorganisms were quantified and visualized using scanning electron microscopy (SEM); DAPI and live/dead staining. The lowest bacterial count of E. faecalis was detected on BES and the highest on B1a. The fewest vital C. albicans strains (42.22%) were detected on B2a surfaces, while most E. faecalis and S. aureus strains (approximately 80%) were vital overall. Compared to BES; coated and uncoated zirconia substrata exhibited no anti-adhesive properties. Further improvement of the material surface characteristics is essential. PMID:28788415

  1. Mechanism of Collaborative Enhancement of Binding of Paired Antibodies to Distinct Epitopes of Platelet Endothelial Cell Adhesion Molecule-1.

    Science.gov (United States)

    Kiseleva, Raisa; Greineder, Colin F; Villa, Carlos H; Hood, Elizabeth D; Shuvaev, Vladimir V; Sun, Jing; Chacko, Ann-Marie; Abraham, Valsamma; DeLisser, Horace M; Muzykantov, Vladimir R

    2017-01-01

    Monoclonal antibodies (mAbs) directed to extracellular epitopes of human and mouse Platelet Endothelial Cell Adhesion Molecule-1 (CD31 or PECAM-1) stimulate binding of other mAbs to distinct adjacent PECAM-1 epitopes. This effect, dubbed Collaborative Enhancement of Paired Affinity Ligands, or CEPAL, has been shown to enhance delivery of mAb-targeted drugs and nanoparticles to the vascular endothelium. Here we report new insights into the mechanism underlying this effect, which demonstrates equivalent amplitude in the following models: i) cells expressing a full length PECAM-1 and mutant form of PECAM-1 unable to form homodimers; ii) isolated fractions of cellular membranes; and, iii) immobilized recombinant PECAM-1. These results indicate that CEPAL is mediated not by interference in cellular functions or homophilic PECAM-1 interactions, but rather by conformational changes within the cell adhesion molecule induced by ligand binding. This mechanism, mediated by exposure of partially occult epitopes, is likely to occur in molecules other than PECAM-1 and may represent a generalizable phenomenon with valuable practical applications.

  2. MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development.

    Science.gov (United States)

    Lu, Cecilia S; Zhai, Bo; Mauss, Alex; Landgraf, Matthias; Gygi, Stephen; Van Vactor, David

    2014-09-26

    Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development in Drosophila. However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labelling in vivo and comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins.

  3. Expression of adhesion molecules, chemokines and matrix metallo- proteinases (MMPs) in viable and degenerating stage of Taenia solium metacestode in swine neurocysticercosis.

    Science.gov (United States)

    Singh, Satyendra K; Singh, Aloukick K; Prasad, Kashi N; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Tripathi, Mukesh; Gupta, Rakesh K; Husain, Nuzhat

    2015-11-30

    Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated.

  4. Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis.

    Science.gov (United States)

    Guazzone, V A; Jacobo, P; Denduchis, B; Lustig, L

    2012-05-01

    The testis is considered an immunologically privileged site where germ cell antigens are protected from autoimmune attack. Yet in response to infections, inflammatory diseases, or trauma, there is an influx of leukocytes to testicular interstitium. Interactions between endothelial cells (EC) and circulating leukocytes are implicated in the initiation and evolution of inflammatory processes. Chemokines are a family of chemoattractant cytokines characterized by their ability to both recruit and activate cells. Thus, we investigated the expression of CCL3, its receptors, and adhesion molecules CD31 and CD106 in an in vivo model of experimental autoimmune orchitis (EAO). In EAO, the highest content of CCL3 in testicular fluid coincides with onset of the disease. However, CCL3 released in vitro by testicular macrophages is higher during the immunization period. The specific chemokine receptors, CCR1 and CCR5, were expressed by testicular monocytes/macrophages and an increased number of CCR5+ cells was associated with the degree of testicular lesion. EC also play an essential role by facilitating leukocyte recruitment via their ability to express cell surface adhesion molecules that mediate interactions with leukocytes in the bloodstream. Rats with EAO showed a significant increase in the percentage of CD31+ EC that upregulate the expression of CD106. The percentage of leukocytes isolated from peripheral blood and lymph nodes expressing CD49d (CD106 ligand) also increases during orchitis. These data suggest that cell adhesion molecules, in conjunction with chemokines, contribute to the formation of a chemotactic gradient within the testis, causing the leukocyte infiltration characteristic of EAO histopathology.

  5. Chronic Restraint Stress Induces an Isoform-Specific Regulation on the Neural Cell Adhesion Molecule in the Hippocampus

    Science.gov (United States)

    Touyarot, K.; Sandi, C.

    2002-01-01

    Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippoampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored; this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events. PMID:12757368

  6. Antidiabetic Rosiglitazone Reduces Soluble Intercellular Adhesion Molecule-1 Level in Type 2 Diabetic Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Guang Wang

    2008-01-01

    Full Text Available Background. We investigated the level of soluble adhesion molecules in diabetic patients and the effect of the peroxisome proliferator-activated receptor-γ (PPAR-γ agonist rosiglitazone on plasma levels of adhesion molecules and an inflammation marker in type 2 diabetic patients with coronary artery disease (CAD after percutaneous coronary intervention (PCI. Methods. A total of 116 diabetic patients with CAD who had undergone PCI were randomized to receive rosiglitazone (4 mg/d or not for 6 months. Plasma levels of soluble intercellular adhesion molecules (sICAM-1 and P-selectin (sP-selectin were measured on ELISA. Results. After 6-month rosiglitazone treatment, plasma levels of sICAM-1 were lower than baseline and control group levels (370.4 (332.4–421.9 pg/mL versus 423.5 (327.4–500.3 pg/mL and 404.6 (345.2–483.4 pg/mL, P<.001. In addition, plasma levels of C-reactive protein were significantly reduced from baseline levels. However, plasma level of sP-selectin was not significantly lowered with rosiglitazone treatment than with control treatment after 6-month follow-up. Conclusions. Rosiglitazone reduces chronic inflammatory responses and improves levels of markers of endothelial dysfunction in patients with diabetes and CAD. PPAR-γ agonist may have a beneficial effect on the vascular endothelium through its anti-inflammatory mechanism and may be useful as therapy in patients undergoing PCI.

  7. P-selectin, endocan, and some adhesion molecules in obese children and adolescents with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Ustyol, Ala; Aycan Ustyol, Esra; Gurdol, Figen; Kokali, Funda; Bekpınar, Seldag

    2017-05-01

    There is increasing evidence for a direct relationship between the vascular system and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate endocan and adhesion molecules such as P-selectin derived from the endothelium and platelets in obese children and adolescents with NAFLD. One hundred obese patients and 40 lean controls were enrolled. The obese subjects were divided into two subgroups based on the presence or absence of fatty liver. Blood samples were assayed for endocan, P-selectin, platelet-derived growth factor (PDGF), intercellular cell adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Obese patients with NAFLD presented higher ALT and insulin levels, as well as more profound dyslipidemia when compared with their counterparts without NAFLD. Serum levels of high-sensitivity C-reactive protein, VCAM-1 and ICAM-1 were found increased in both obese groups, regardless of NAFLD. In obese subjects with NAFLD, decreased P-selectin levels (51.6 ± 4.14 ng/mL) were detected as compared with the obese (72.3 ± 4.23) and control (74.2 ± 6.97) subjects. Furthermore, circulating P-selectin levels were closely associated with endocan levels (r = 0.852, p obesity leads to vascular inflammation and therefore may cause a predisposition to atherosclerosis at an early age. The possible outcome of decreased P-selectin levels with NAFLD development must be further investigated.

  8. Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions

    Science.gov (United States)

    Schulz, Florian; Lutz, David; Rusche, Norman; Bastús, Neus G.; Stieben, Martin; Höltig, Michael; Grüner, Florian; Weller, Horst; Schachner, Melitta; Vossmeyer, Tobias; Loers, Gabriele

    2013-10-01

    The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1 sequence of the third fibronectin type III domain of murine L1 was identified and conjugated to gold nanoparticles (AuNPs) to obtain constructs that interact homophilically with the extracellular domain of L1 and trigger the cognate beneficial L1-mediated functions. Covalent conjugation was achieved by reacting mixtures of two cysteine-terminated forms of this L1 peptide and thiolated poly(ethylene) glycol (PEG) ligands (~2.1 kDa) with citrate stabilized AuNPs of two different sizes (~14 and 40 nm in diameter). By varying the ratio of the L1 peptide-PEG mixtures, an optimized layer composition was achieved that resulted in the expected homophilic interaction of the AuNPs. These AuNPs were stable as tested over a time period of 30 days in artificial cerebrospinal fluid and interacted with the extracellular domain of L1 on neurons and Schwann cells, as could be shown by using cells from wild-type and L1-deficient mice. In vitro, the L1-derivatized particles promoted neurite outgrowth and survival of neurons from the central and peripheral nervous system and stimulated Schwann cell process formation and proliferation. These observations raise the hope that, in combination with other therapeutic approaches, L1 peptide-functionalized AuNPs may become a useful tool to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1

  9. Clinical evaluation of serum concentrations of intercellular adhesion molecule-1 in patients with colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Kang; Fang Wang; Jin-Dong Xie; Jun Cao; Pei-Zhong Xian

    2005-01-01

    AIM: To investigate the correlation between the serum soluble intercellular adhesion molecule-1 (sICAM-1) and the clinicopathologic features and to evaluate the possible prognostic significance of sICAM-1 concentration in colorectal cancer.METHODS: A total of 56 patients (mean age 57.3 years)having transitional cell carcinoma of the colorectal and 25 control patients (mean age 42.6 years) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery. Sera were obtained by centrifugation, and stored at -80 ℃ until assay. Serumconcentrations of ICAM-1 were measured with enzymelinked immunoassay. Differences between the two groups were analyzed by Student's t-test.RESULTS: No significant increase of serum sICAM-1 could be demonstrated in the Dukes A1 patients (352.63±61.82μg/L) compared to the control group (345.72±49.81 μg/L,P>0.05), Dukes A1 patients (352.63±61.82 μg/L)compared to Dukes A2,3 patients (491.17±86.36 μg/L,P<0.05). Furthermore, the patients with Dukes B had significantly higher serum concentrations of sICAM-1than those of the control group (496.82±93.04 μg/L vs 345.72±49.81 μg/L, P<0.01). Compared with Dukes A2,3,B colorectal cancer patients, patients with more advanced clinical stage (Dukes C and D) had higher levels of sICAM-1 (743.68±113.74 μg/L vs491.17±86.36 μg/L and 496.82±93.04 μg/L, P<0.001). The difference was statistically significant in sICAM-1 levels between patients with positive lymph node status and those without lymph node involvement (756.25±125.57 μg/L vs445.62±69.18 μg/L, P<0.001).Patients with poorly differentiated colorectal cancer had a higher level of sICAM-1 than those with differentiated and highly differentiated cancer (736.49±121.97 μg/Lvs 410.23±67.47 μg/L, P<0.001).CONCLUSION: In this study, serum ICAM-1 levels were found to be related to tumor presence, clinical stages,and grade. Increased ICAM-1 in patients with colorectal cancer which should

  10. H-1 and N-15 resonance assignment of the second fibronectin type III module of the neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Kiselyov, Vladislav V; Berezin, Vladimir; Bock, Elisabeth;

    2008-01-01

    We report here the NMR assignment of the second fibronectin type III module of the neural cell adhesion molecule (NCAM). This module has previously been shown to interact with the fibroblast growth factor receptor (FGFR), and the FGFR-binding site was mapped by NMR to the FG-loop region...... of the module. The FG-loop region also contains a putative nucleotide-binding motif, which was shown by NMR to interact with ATP. Furthermore, ATP was demonstrated to inhibit binding of the second F3 module of NCAM to FGFR....

  11. Soluble Inter-Cellular Adhesion Molecule-1 in Urban Asian North Indians: Relationships with Anthropometric and Metabolic Covariates

    Directory of Open Access Journals (Sweden)

    Astha Sethi

    2002-01-01

    Full Text Available Background: High prevalence of diabetes, obesity, and dyslipidemias in people belonging to poor socio-economic strata in urban slums of northern India has been recorded recently. To assess whether this population has high levels of soluble intercellular adhesion molecule-1 (sICAM-1, a cytokine involved in the pathogenesis of atherosclerosis, we investigated subjects belonging to poor socio-economic strata in urban slums and compared them to healthy control subjects from non-slum urban areas of New Delhi.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    -binding sites (HBS and CBS, respectively) in IgII coincide, and that this site overlaps with the homophilic binding site. Using NMR and surface plasmon resonance (SPR) analyses we demonstrate that interaction between IgII and heparin indeed interferes with the homophilic interaction between IgI and Ig......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...

  13. Physiology and pathophysiology of selectins, integrins, and IgSF cell adhesion molecules focusing on inflammation. A paradigm model on infectious endocarditis.

    Science.gov (United States)

    Golias, Christos; Batistatou, Anna; Bablekos, Georgios; Charalabopoulos, Alexandros; Peschos, Dimitrios; Mitsopoulos, Panagiotis; Charalabopoulos, Konstantinos

    2011-06-01

    The development of adhesion bonds, either among cells or among cells and components of the extracellular matrix, is a crucial process. These interactions are mediated by some molecules collectively known as adhesion molecules (CAMs). CAMs are ubiquitously expressed proteins playing a central role in controlling cell migration, proliferation, survival, and apoptosis. Besides their key function in physiological maintenance of tissue integrity, CAMs play an eminent role in various pathological processes such as cardiovascular disorders, atherogenesis, atherosclerotic plaque progression and regulation of the inflammatory response. CAMs such as selectins, integrins, and immunoglobulin superfamily take part in interactions between leukocyte and vascular endothelium (leukocyte rolling, arrest, firm adhesion, migration). Experimental data and pathologic observations support the assumption that pathogenic microorganisms attach to vascular endothelial cells or sites of vascular injury initiating intravascular infections. In this review a paradigm focusing on cell adhesion molecules pathophysiology and infective endocarditis development is given.

  14. Unraveling the Secrets of Bacterial Adhesion Organelles Using Single-Molecule Force Spectroscopy

    Science.gov (United States)

    Axner, Ove; Björnham, Oscar; Castelain, Mickaël; Koutris, Efstratios; Schedin, Staffan; Fällman, Erik; Andersson, Magnus

    Many types of bacterium express micrometer-long attachment organelles (so-called pili) whose role is to mediate adhesion to host tissue. Until recently, little was known about their function in the adhesion process. Force-measuring optical tweezers (FMOT) have since then been used to unravel the biomechanical properties of various types of pili, primarily those from uropathogenic E. coli, in particular their force-vs.-elongation response, but lately also some properties of the adhesin are situated at the distal end of the pilus. This knowledge provides an understanding of how piliated bacteria can sustain external shear forces caused by rinsing processes, e.g., urine flow. It has been found that many types of pilus exhibit unique and complex force-vs.-elongation responses. It has been conjectured that their dissimilar properties impose significant differences in their ability to sustain external forces and that different types of pilus therefore have dissimilar predisposition to withstand different types of rinsing conditions. An understanding of these properties is of high importance since it can serve as a basis for finding new means to combat bacterial adhesion, including that caused by antibiotic-resistance bacteria. This work presents a review of the current status of the assessment of biophysical properties of individual pili on single bacteria exposed to strain/stress, primarily by the FMOT technique. It also addresses, for the first time, how the elongation and retraction properties of the rod couple to the adhesive properties of the tip adhesin.

  15. Virus-activated T cells regulate expression of adhesion molecules on endothelial cells in sites of infection

    DEFF Research Database (Denmark)

    Marker, O; Scheynius, A; Christensen, Jan Pravsgaard

    1995-01-01

    was the inflammatory reaction dependent on the presence of CD8+ cells, but these cells also appeared to be required for maximal upregulation of ICAM-1 and VCAM-1 on the endothelial cells. These results indicate that virus-specific CD8+ T cells are crucially involved in regulating the inflammatory reaction through......To study the role of cell adhesion molecules in the fatal CD8+ T-cell mediated meningitis which is induced by intracerebral infection with lymphocytic choriomeningitis virus, the expression of relevant molecules on inflammatory cells and local endothelium was analyzed immunohistochemically. Most...... inflammatory cells were strongly positive for LFA-1, VLA-4, Pgp-1 and ICAM-1. Expression of ICAM-1 and VCAM-1 was upregulated on the endothelial cells in immunocompetent mice, but not in T-cell deficient nude mice. Analysis of mice deficient in either CD4+ or CD8+ T cells, revealed that not only...

  16. Age dependency of the composition of immunocompetent cells and the expression of adhesion molecules in rat laryngeal mucosa.

    Science.gov (United States)

    Jecker, P; Ptok, M; Pabst, R; Westermann, J

    1996-06-01

    Clinical evidence shows that laryngeal infections in infants differ significantly from those in adults. Therefore, the composition of the mucosal immune system (granulocytes, macrophages, dendritic cells, natural killer cells, and T and B lymphocytes) and the epithelial expression of class II-MHC molecules and adhesion molecules ICAM-1, VCAM-1, and E-selectin were studied in the larynx of newborn, 5-week-old, and 3-year-old rats. With the exception of macrophages, the immunocompetent cells began to immigrate into the laryngeal mucosa after birth, indicating that the laryngeal mucosa in newborn rats is immature. In contrast, ICAM-1 was already expressed. The number of immunocompetent cells and the expression of epithelial class II-MHC and ICAM-1 increased with age. Immunocompetent cells and epithelial class II-MHC and ICAM-1 expression were mainly detected in the subglottic region, but were almost absent in the vocal fold region.

  17. New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Jouet, M.; Kenwick, S. [Univ. of Cambridge (United Kingdom); Moncla, A. [Hopital d`Enfants de la Timone, Marseillas (United Kingdom)] [and others

    1995-06-01

    The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function. 39 refs., 5 figs., 3 tabs.

  18. Junctional adhesion molecule 2 mediates the interaction between hatched blastocyst and luminal epithelium: induction by progesterone and LIF.

    Directory of Open Access Journals (Sweden)

    Ren-Wei Su

    Full Text Available BACKGROUND: Junctional adhesion molecule 2 (Jam2 is a member of the JAM superfamily. JAMs are localized at intercellular contacts and participated in the assembly and maintenance of junctions, and control of cell permeability. Because Jam2 is highly expressed in the luminal epithelium on day 4 of pregnancy, this study was to determine whether Jam2 plays a role in uterine receptivity and blastocyst attachment in mouse uterus. METHODOLOGY/PRINCIPAL FINDINGS: Jam2 is highly expressed in the uterine luminal epithelium on days 3 and 4 of pregnancy. Progesterone induces Jam2 expression in ovariectomized mice, which is blocked by progesterone antagonist RU486. Jam2 expression on day 4 of pregnancy is also inhibited by RU486 treatment. Leukemia inhibitory factor (LIF up-regulates Jam2 protein in isolated luminal epithelium from day 4 uterus, which is blocked by S3I-201, a cell-permeable inhibitor for Stat3 phosphorylation. Under adhesion assay, recombinant Jam2 protein increases the rate of blastocyst adhesion. Both soluble recombinant Jam2 and Jam3 can reverse this process. CONCLUSION: Jam2 is highly expressed in the luminal epithelium of receptive uterus and up-regulated by progesterone and LIF via tyrosine phosphorylation of Stat3. Jam2 may play a role in the interaction between hatched blastocyst and receptive uterus.

  19. Characterization of mechanics and cytocompatibility of fibrin-genipin annulus fibrosus sealant with the addition of cell adhesion molecules.

    Science.gov (United States)

    Guterl, Clare C; Torre, Olivia M; Purmessur, Devina; Dave, Khyati; Likhitpanichkul, Morakot; Hecht, Andrew C; Nicoll, Steven B; Iatridis, James C

    2014-09-01

    There is an unmet clinical need for a biomaterial sealant capable of repairing small annulus fibrosus (AF) defects. Causes of these defects include painful intervertebral disc herniations, microdiscectomy procedures, morbidity associated with needle puncture injury from discography, and future nucleus replacement procedures. This study describes the enhancements of a fibrin gel through genipin crosslinking (FibGen) and the addition of the cell adhesion molecules (CAMs), fibronectin and collagen. The gel's performance as a potential AF sealant is assessed using a series of in vitro tests. FibGen gels with CAMs had equivalent adhesive strength, gene expression, cytomorphology, and cell proliferation as fibrin alone. However, FibGen gels had enhanced material behaviors that were tunable to higher shear stiffness values and approximated human annulus tissue as compared with fibrin alone, were more dimensionally stable, and had a slower in vitro degradation rate. Cytomorphology of human AF cells cultured on FibGen gels exhibited increased elongation compared with fibrin alone, and the addition of CAMs to FibGen did not significantly affect elongation. This FibGen gel offers the promise of being used as a sealant material to repair small AF defects or to be used in combination with other biomaterials as an adhesive for larger defects.

  20. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  1. Structure and Stability of Interstellar Molecule C3S

    Institute of Scientific and Technical Information of China (English)

    YU,Hai-Tao(于海涛); FU,Hong-Gang(傅宏刚); CHI,Yu-Juan(池玉娟); HUANG,Xu-Ri(黄旭日); LI,Ze-Sheng(李泽生); SUN,Jia-Zhong(孙家钟)

    2002-01-01

    The singlet and triplet potential energy surfaces of interstellar molecule C3S are predicted at the UB3LYP/6-311 (d) and UCCSD(T)/6-311 + G(2df) (single-point) levels. The linear singlet isomer CCCS with 1 ∑ + electronic state is found to be thermodynamically and kinetically the most stable species on the singlet surface followed by other four singiet isomers, which are unstable on the basis of calculated results. On the triplet sur face, the lowest-lying species, which lies 248.79 kJ/mol above linear singlet species CCCS, is chain CCCS connectivity with 3A' electronic state. Other four triplet isomers can be considered as unstable species by means of transition state and potential energy surface scan technologies. The structures, vibrational frequencies, dipole moments and rotational constants of all optimized species are also calculated.

  2. Identification of neural cell adhesion molecule L1-derived neuritogenic ligands of the fibroblast growth factor receptor

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Li, Shizhong; Kiselyov, Vladislav

    2009-01-01

    The neural cell adhesion molecule L1 plays an important role in axon growth, neuronal survival, and synaptic plasticity. We recently demonstrated that the L1 fibronectin type III (FN3) modules interact directly with the fibroblast growth factor (FGF) receptor (FGFR). Sequence alignment of individ......The neural cell adhesion molecule L1 plays an important role in axon growth, neuronal survival, and synaptic plasticity. We recently demonstrated that the L1 fibronectin type III (FN3) modules interact directly with the fibroblast growth factor (FGF) receptor (FGFR). Sequence alignment...... of individual L1 FN3 modules with various FGFs suggested that four sequence motifs located in the third and fifth L1 FN3 modules might be involved in interactions with FGFR. The present study found that corresponding synthetic peptides, termed elcamins 1, 2, 3, and 4, bind and activate FGFR in the absence...... of FGF1. Conversely, in the presence of FGF1, elcamins inhibited receptor phosphorylation, indicating that the peptides are FGFR partial agonists. Elcamins 1, 3, and 4 dose dependently induced neurite outgrowth in cultured primary cerebellar neurons. The neuritogenic effect of elcamins was dependent...

  3. Combination of engineered neural cell adhesion molecules and GDF-5 for improved neurite extension in nerve guide concepts.

    Science.gov (United States)

    Niere, Marc; Braun, Bettina; Gass, Rea; Sturany, Sabine; Volkmer, Hansjürgen

    2006-06-01

    Current therapeutical approaches for the treatment of severe lesions in the peripheral nervous system rely on the use of autologous tissue or the body's own Schwann cells. However, these approaches are limited and alternative strategies for peripheral nerve regeneration are required. Here we evaluate combinations of a variety of neuronal regeneration factors including engineered cell adhesion molecules and growth factors in embryonic model neurons to test the possible improvement of artificial nerve guides by cooperative mechanisms. Cell adhesion molecules L1 and neurofascin synergistically promote neurite elongation. The outgrowth promoting properties of both proteins can be combined and further increased within one chimeric protein. Addition of growth and differentiation factor 5 (GDF-5) further enhances neurite outgrowth in a substrate-independent manner. This effect is not due to a protective mode of action of GDF-5 against pro-apoptotic stimuli. Consequently, the study supports the idea that different modes of action of pro-regenerative factors may contribute synergistically to neurite outgrowth and emphasizes the applicability of combinations of proteins specifically involved in development of the nervous system for therapeutical approaches.

  4. Polyclonal neural cell adhesion molecule antibody prolongs the effective duration time of botulinum toxin in decreasing muscle strength.

    Science.gov (United States)

    Guo, Yan; Pan, Lizhen; Liu, Wuchao; Pan, Yougui; Nie, Zhiyu; Jin, Lingjing

    2015-11-01

    This study aimed to investigate if the effective duration time of botulinum toxin A (Btx-A) could be prolonged by polyclonal neural cell adhesion molecule antibody (P-NCAM-Ab). 175 male SD rats were randomly divided into three major groups: control group (n = 25), Btx-A group (n = 25), and P-NCAM-Ab groups. P-NCAM-Ab groups were composed of five sub-groups, with 25 rats each in the dose-response study. Muscle strength of rat lower limbs was determined using a survey system. The expressions of muscle-specific receptor tyrosine kinase (MuSK) and neural cell adhesion molecule (NCAM) were determined by real-time polymerase chain reactions (RT-PCR) and western blotting (WB). The muscle strength was significantly decreased by Btx-A in Btx-A/P-NCAM-Ab groups compared with normal control group. Besides, the muscle strength of P-NCAM-Ab group was significantly decreased compared with the Btx-A group. The recovery time of muscle strength in P-NCAM-Ab group was significantly longer compared with Btx-A group. RT-PCR and WB assay showed that PNCAM-Ab delayed the increase of MuSK and NCAM after Btx-A injection. P-NCAM-Ab prolongs the effective duration time of Btx-A in decreasing muscle strength, which could provide a novel enhancement in clinical application.

  5. [Expression and significance of adhesion molecules CD62P and CD44 in peripheral blood of infants with bronchiolitis].

    Science.gov (United States)

    Zou, Li-Ping; Wang, Wei; Zhang, Yan-Li; Zhang, Yan; Wang, Li

    2015-11-01

    To explore the expression and significance of the adhesion molecules CD62P and CD44 in the peripheral blood of infants with bronchiolitis. Thirty-three infants with bronchiolitis in the acute phase and 19 infants with bronchiolitis in the recovery phase, who were hospitalized between November 2014 and May 2015, were enrolled. Thirty infants with bronchopneumonia and 26 infants without infection were enrolled as the bronchopneumonia group and the control group, respectively. The CD62P expression in the peripheral blood of each group was measured by flow cytometry, and the CD44 level in serum was determined using ELISA. The levels of the adhesion molecules CD62P and CD44 in the bronchiolitis group in the acute phase were significantly higher than those in the bronchiolitis group in the recovery phase, the bronchopneumonia group, and the control group (Pbronchiolitis group in the recovery phase were also significantly higher than those in the control group (Pbronchiolitis group in the acute phase, there was a positive correlation between CD62P expression and serum CD44 level (r=0.91; Pbronchiolitis, and their levels can reflect the severity of inflammatory response in infants with bronchiolitis.

  6. Improved Adhesion, Growth and Maturation of Vascular Smooth Muscle Cells on Polyethylene Grafted with Bioactive Molecules and Carbon Particles

    Directory of Open Access Journals (Sweden)

    Martina Blazkova

    2009-10-01

    Full Text Available High-density polyethylene (PE foils were modified by an Ar+ plasma discharge and subsequent grafting with biomolecules, namely glycine (Gly, polyethylene glycol (PEG, bovine serum albumin (BSA, colloidal carbon particles (C or BSA and C (BSA + C. As revealed by atomic force microscopy (AFM, goniometry and Rutherford Backscattering Spectroscopy (RBS, the surface chemical structure and surface morphology of PE changed dramatically after plasma treatment. The contact angle decreased for the samples treated by plasma, mainly in relation to the formation of oxygen structures during plasma irradiation. A further decrease in the contact angle was obvious after glycine and PEG grafting. The increase in oxygen concentration after glycine and PEG grafting proved that the two molecules were chemically linked to the plasma-activated surface. Plasma treatment led to ablation of the PE surface layer, thus the surface morphology was changed and the surface roughness was increased. The materials were then seeded with vascular smooth muscle cells (VSMC derived from rat aorta and incubated in a DMEM medium with fetal bovine serum. Generally, the cells adhered and grew better on modified rather than on unmodified PE samples. Immunofluorescence showed that focal adhesion plaques containing talin, vinculin and paxillin were most apparent in cells on PE grafted with PEG or BSA + C, and the fibres containing α-actin, β-actin or SM1 and SM2 myosins were thicker, more numerous and more brightly stained in the cells on all modified PE samples than on pristine PE. An enzyme-linked immunosorbent assay (ELISA revealed increased concentrations of focal adhesion proteins talin and vinculin and also a cytoskeletal protein β-actin in cells on PE modified with BSA + C. A contractile protein α-actin was increased in cells on PE grafted with PEG or Gly. These results showed that PE activated with plasma and subsequently grafted with bioactive molecules and colloidal C

  7. Improved adhesion, growth and maturation of vascular smooth muscle cells on polyethylene grafted with bioactive molecules and carbon particles.

    Science.gov (United States)

    Parizek, Martin; Kasalkova, Nikola; Bacakova, Lucie; Slepicka, Petr; Lisa, Vera; Blazkova, Martina; Svorcik, Vaclav

    2009-11-20

    High-density polyethylene (PE) foils were modified by an Ar(+) plasma discharge and subsequent grafting with biomolecules, namely glycine (Gly), polyethylene glycol (PEG), bovine serum albumin (BSA), colloidal carbon particles (C) or BSA and C (BSA + C). As revealed by atomic force microscopy (AFM), goniometry and Rutherford Backscattering Spectroscopy (RBS), the surface chemical structure and surface morphology of PE changed dramatically after plasma treatment. The contact angle decreased for the samples treated by plasma, mainly in relation to the formation of oxygen structures during plasma irradiation. A further decrease in the contact angle was obvious after glycine and PEG grafting. The increase in oxygen concentration after glycine and PEG grafting proved that the two molecules were chemically linked to the plasma-activated surface. Plasma treatment led to ablation of the PE surface layer, thus the surface morphology was changed and the surface roughness was increased. The materials were then seeded with vascular smooth muscle cells (VSMC) derived from rat aorta and incubated in a DMEM medium with fetal bovine serum. Generally, the cells adhered and grew better on modified rather than on unmodified PE samples. Immunofluorescence showed that focal adhesion plaques containing talin, vinculin and paxillin were most apparent in cells on PE grafted with PEG or BSA + C, and the fibres containing alpha-actin, beta-actin or SM1 and SM2 myosins were thicker, more numerous and more brightly stained in the cells on all modified PE samples than on pristine PE. An enzyme-linked immunosorbent assay (ELISA) revealed increased concentrations of focal adhesion proteins talin and vinculin and also a cytoskeletal protein beta-actin in cells on PE modified with BSA + C. A contractile protein alpha-actin was increased in cells on PE grafted with PEG or Gly. These results showed that PE activated with plasma and subsequently grafted with bioactive molecules and colloidal C

  8. The role of photobiomodulation on gene expression of cell adhesion molecules in diabetic wounded fibroblasts in vitro.

    Science.gov (United States)

    Ayuk, Sandra M; Abrahamse, Heidi; Houreld, Nicolette N

    2016-08-01

    Cell adhesion molecules (CAMs) are cell surface glycoproteins that facilitate cell-cell contacts and adhesion with the extracellular matrix (ECM). Cellular adhesion is affected by various disease conditions, such as diabetes mellitus (DM) and inflammation. Photobiomodulation (PBM) stimulates biological processes and expression of these cellular molecules. The aim of this experimental work was to demonstrate the role of PBM at 830nm on CAMs in diabetic wounded fibroblast cells. Isolated human skin fibroblast cells were used. Normal (N-) and diabetic wounded (DW-) cells were irradiated with a continuous wave diode laser at 830nm with an energy density of 5J/cm(2). Real time reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine the relative gene expression of 39 CAMs 48h post-irradiation. Normalized expression levels from irradiated cells were calculated relative to non-irradiated control cells according to the 2^(-ΔΔCt) method. Thirty-one genes were significantly regulated in N-cells (28 were genes up-regulated and three genes down-regulated), and 22 genes in DW-cells (five genes were up-regulated and 17 genes down-regulated). PBM induced a stimulatory effect on various CAMs namely cadherins, integrins, selectins and immunoglobulins, and hence may be used as a complementary therapy in advancing treatment of non-healing diabetic ulcers. The regulation of CAMs as well as evaluating the role of PBM on the molecular effects of these genes may expand knowledge and prompt further research into the cellular mechanisms in diabetic wound healing that may lead to valuable clinical outcomes.

  9. Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and serum inflammatory cytokines in atherosclerotic rabbit model

    Institute of Scientific and Technical Information of China (English)

    Muwei Li; Xianpei Wang; Lei Yang; Chuanyu Gao; Yexin Ma

    2008-01-01

    Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P<0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2

  10. Early Detection of Junctional Adhesion Molecule-1 (JAM-1 in the Circulation after Experimental and Clinical Polytrauma

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    Stephanie Denk

    2015-01-01

    Full Text Available Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1 was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18 during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score. The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.

  11. Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma.

    Science.gov (United States)

    Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M; Messerer, David A C; Radermacher, Peter; Weiss, Manfred; Kalbitz, Miriam; Ehrnthaller, Christian; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

    2015-01-01

    Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.

  12. 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.

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

    2009-10-01

    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 degrees 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 Echinoid (Fred) act throughout ommatidial rotation to modulate the degree of ommatidial precursor movement. We propose that differential levels of Ed and Fred between stationary and rotating cells at the initiation of rotation create a permissive environment for cell movement, and that uniform levels in these two populations later contribute to stopping the movement. Based on genetic data, we propose that ed and fred impart a second, independent, ;brake-like' contribution to this process via Egfr signaling. Ed and Fred are localized in largely distinct and dynamic patterns throughout rotation. However, ed and fred are required in only a subset of cells - photoreceptors R1, R7 and R6 - for normal rotation, cells that have only recently been linked to a role in planar cell polarity (PCP). This work also provides the first demonstration of a requirement for cone cells in the ommatidial rotation aspect of PCP. ed and fred also genetically interact with the PCP genes, but affect only the degree-of-rotation aspect of the PCP phenotype. Significantly, we demonstrate that at least one PCP protein, Stbm, is required in R7 to control the degree of ommatidial rotation.

  13. Serum leptin levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in normal pregnancy and preeclampsia

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    Karádi István

    2011-09-01

    Full Text Available Abstract Objective In this study, we determined circulating levels of C-reactive protein, several cytokines, chemokines, adhesion molecules and angiogenic factors along with those of leptin in healthy non-pregnant and pregnant women and preeclamptic patients, and investigated whether serum leptin levels were related to the clinical characteristics and measured laboratory parameters of the study participants. Methods Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Levels of leptin and transforming growth factor (TGF-beta1 in maternal sera were assessed by ELISA. 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, interferon-gamma-inducible protein (IP-10, monocyte chemotactic protein (MCP-1, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 were determined by multiplex suspension array. Serum C-reactive protein (CRP concentrations were measured by an autoanalyzer. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1 and biologically active placental growth factor (PlGF levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied. Results There were significant differences in most of the measured laboratory parameters among the three study groups except for serum IL-1beta and TGF-beta1 levels. Serum leptin levels were significantly higher in preeclamptic patients and healthy pregnant women than in healthy non-pregnant women. Additionally, preeclamptic patients had significantly higher leptin levels as compared to healthy pregnant women. Serum leptin levels were independently associated with BMI in healthy non-pregnant women. In healthy pregnant women, both BMI and serum CRP concentrations showed significant positive linear

  14. Effects of nitrogen dioxide on the expression of intercellular adhesion molecule-1, neutrophil adhesion, and cytotoxicity: studies in human bronchial epithelial cells.

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    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2007-02-01

    Nitrogen Dioxide (NO2) is a product of high-temperature combustion and an environmental oxidant of concern. We have recently reported that early changes in NO2-exposed human bronchial epithelial cells are causally linked to increased generation of proinflammatory mediators, such as nitric oxide/nitrite and cytokines like interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-8. The objective of the present in vitro study was to further delineate the cellular mechanisms of NO2-mediated toxicity, and to define the nature of cell death that ensues upon exposure of normal human bronchial epithelial (NHBE) cells to a brief high dose of NO2. Our results demonstrate that the NHBE cells undergo apoptotic cell death during the early post-NO2 period, but this is independent of any significant increase in caspase-3 activity. However, necrotic cell death was more prevalent at later time intervals. Interestingly, an increased expression of HO-1, a redox-sensitive stress protein, was observed in NO2-exposed NHBE cells at 24 h. Since neutrophils (PMNs) play an active role in acute lung inflammation and resultant oxidative injury, we also investigated changes in human PMN-NHBE cell interactions. As compared to normal cells, increased adhesion of PMNs to NO2-exposed cells was observed, which resulted in an increased NHBE cell death. The latter was also increased in the presence of IL-8 and TNF-alpha + interferon (IFN)-gamma, which correlated with upregulation of intercellular adhesion molecule-1 (ICAM-1). Our results confirmed an involvement of nitric oxide (NO) in NO2-induced cytotoxicity. By using NO synthase inhibitors such as L-NAME and 3-aminoguanidine (AG), a significant decrease in cell death, PMN adhesion, and ICAM-1 expression was observed. These findings indicate a role for the L-arginine/NO synthase pathway in the observed NO2-mediated toxicity in NHBE cells. Therapeutic strategies aimed at controlling excess generation of NO and/or inflammatory cytokines may

  15. Expression of the immunoglobulin superfamily cell adhesion molecules in the developing spinal cord and dorsal root ganglion.

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    Gu, Zirong; Imai, Fumiyasu; Kim, In Jung; Fujita, Hiroko; Katayama, Kei ichi; Mori, Kensaku; Yoshihara, Yoshihiro; Yoshida, Yutaka

    2015-01-01

    Cell adhesion molecules belonging to the immunoglobulin superfamily (IgSF) control synaptic specificity through hetero- or homophilic interactions in different regions of the nervous system. In the developing spinal cord, monosynaptic connections of exquisite specificity form between proprioceptive sensory neurons and motor neurons, however, it is not known whether IgSF molecules participate in regulating this process. To determine whether IgSF molecules influence the establishment of synaptic specificity in sensory-motor circuits, we examined the expression of 157 IgSF genes in the developing dorsal root ganglion (DRG) and spinal cord by in situ hybridization assays. We find that many IgSF genes are expressed by sensory and motor neurons in the mouse developing DRG and spinal cord. For instance, Alcam, Mcam, and Ocam are expressed by a subset of motor neurons in the ventral spinal cord. Further analyses show that Ocam is expressed by obturator but not quadriceps motor neurons, suggesting that Ocam may regulate sensory-motor specificity in these sensory-motor reflex arcs. Electrophysiological analysis shows no obvious defects in synaptic specificity of monosynaptic sensory-motor connections involving obturator and quadriceps motor neurons in Ocam mutant mice. Since a subset of Ocam+ motor neurons also express Alcam, Alcam or other functionally redundant IgSF molecules may compensate for Ocam in controlling sensory-motor specificity. Taken together, these results reveal that IgSF molecules are broadly expressed by sensory and motor neurons during development, and that Ocam and other IgSF molecules may have redundant functions in controlling the specificity of sensory-motor circuits.

  16. Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

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    Elzinandes L Azeredo

    2006-06-01

    Full Text Available The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8 express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54, VLA-4, and LFA-1 (CD11a were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.

  17. Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease.

    Science.gov (United States)

    Azeredo, Elzinandes L; Zagne, Sonia M O; Alvarenga, Allan R; Nogueira, Rita M R; Kubelka, Claire F; de Oliveira-Pinto, Luzia M

    2006-06-01

    The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4 and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8) express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54), VLA-4, and LFA-1 (CD11a) were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.

  18. Stability of Soil Carbon Fractions - from molecules to aggregates

    Science.gov (United States)

    Mueller, C. W.; Mueller, K. E.; Freeman, K. H.; Eissenstat, D.; Kögel-Knabner, I.

    2009-12-01

    The turnover of soil organic matter (SOM) is controlled both by its chemical composition, its spatial bioavailability and the association with the mineral phase. Separation by physical fractionation of bulk soils and subsequent chemical analysis of these fractions should give insights to how compositional differences in SOM drive turnover rates of different size-defined carbon pools. The main objective of the study was to elucidate the relative abundance and recalcitrance of lignin and plant lipids (e.g. cutin and suberin) in the course of SOM decomposition within aggregated bulk soils and SOM fractions. By the parallel incubation of physically-separated size fractions and bulk soils of the Ah horizon from a forested soil (Picea abies L.Karst) over a period of 400 days, a unique set of samples was created to study SOM dynamics. We used solid-state 13C-CPMAS NMR spectroscopy and GC-MS (after copper oxide oxidation and solvent extraction) to analyze the composition of the incubated samples. The abundance and isotopic composition (including 13C and 14C) of respired CO2 further enabled us to monitor the dynamics of SOM mineralization. This approach allowed for differentiating between C stabilization of soil fractions due to accessibility/aggregation and to recalcitrance at different scales of resolution (GC-MS, NMR). A relative enrichment of alkyl C and decreasing lignin contents in the order of sand cutin, and suberin monomers measured by GC-MS before and after the incubation indicate selective degradation and preservation patterns at the molecular scale that are rarely observed and are unresolved by NMR analyses. We suggest that the monomer-specific patterns of lignin, cutin, and suberin decomposition facilitate better understanding and modelling of SOM dynamics by providing a tool to potentially separate the influence of input rates from selective preservation on the abundance of these bipolymers in soil.

  19. Lauric acid abolishes interferon-gamma (IFN-γ)-induction ofIntercellular AdhesionMolecule-1 (ICAM-1) andVascularCellAdhesionMolecule-1 (VCAM-1) expression in human macrophages

    Institute of Scientific and Technical Information of China (English)

    Wei-Siong Lim; Mary-Shi-Ying Gan; Melissa-Hui-Ling Ong; Choy-Hoong Chew

    2015-01-01

    Objective:To investigate the effect of different concentrations of lauric acid on Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) expression in IFN-γ stimulated human monocytic THP-1 cell line.Methods:THP-1 cell were cultured using Roswell Park Memorial Institute medium supplemented with 10% fetal bovine serum. THP-1 monocytes were firstly differentiated into macrophages by using phorbol-12-myristate-13-acetate. IFN-γ response test was perfomed and total cellular RNA was extracted using TRI Reagent®LS before q-RT-PCR was carried out. Subsequently, IFN-γ treated THP-1 macrophages were stimulated with increasing doses of lauric acid for another 24 hour, before q-RT-PCR. MTT assay was carried out to investigate the effect of lauric acid on undifferentiated and differentiated THP-1 cells.Results:The mRNA expression levels of ICAM-1 and VCAM-1 were normalized toβ-actin and relatived to the untreated cells. The expressions of ICAM-1 and VCAM-1 were significantly induced in cells treated with 10 ng/mL of IFN-γ. This showed that IFN-γ could up-regulate inflammatory process and may cause atheroma formation. Although lauric acid did not have any significant impact on undifferentiated and differentiated THP-1 cell viability, the normalized fold expressions of ICAM-1 and VCAM-1 in IFN-γ-treated THP-1 macrophages were decreased significantly in a dose dependent manner with the presence of increasing doses of lauric acid.Conclusions:This study successfully proved that lauric acid was able to antagonize the up-regulatory effect of IFN-γ on ICAM-1 and VCAM-1 expressions in THP-1 macrophages. This indicates that lauric acid may be an anti-inflammatory therapeutic and prophylaxis agent for atherosclerosis.

  20. Changes in the vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and c-reactive protein following administration of aqueous extract of piper sarmentosum on experimental rabbits fed with cholesterol diet

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    Al-Mekhlafi Hesham M

    2011-01-01

    Full Text Available Abstract Background Inflammation process plays an important role in the development of atherosclerosis. Hypercholesterolemia is one of the major risk factors for atherosclerosis. The present study aimed to evaluate the effect of aqueous extract of Piper sarmentosum (P.s on inflammatory markers like vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1, and C-reactive protein (CRP. Methods Forty two male New Zealand white rabbits were divided equally into seven groups; (i C- control group fed normal rabbit chow (ii CH- cholesterol diet (1%cholesterol (iii X1- 1% cholesterol with water extract of P.s (62.5 mg/kg (iv X2- 1% cholesterol with water extract of P.s (125 mg/kg (v X3- 1% cholesterol with water extract of P.s (250 mg/kg (vi X4- 1% cholesterol with water extract of P.s (500 mg/kg and (vii SMV group fed with 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg. All animals were treated for 10 weeks. Blood serum was taken for observing the inflammatory markers at the beginning and end of the experiment. Results Rabbits fed with 1% cholesterol diet (CH showed significant increase in the level of VCAM-1, ICAM-1 and CRP compared to the C group. The levels of VCAM-1, ICAM-1 and CRP in the 1% cholesterol group and supplemented with P.s (500 mg/kg were significantly reduced compared to the cholesterol group. Similar results were also reported with simvistatin group. Conclusion These results suggest that the supplementation of Piper sarmentosum extract could inhibit inflammatory markers which in turn could prevent atherosclerosis.

  1. Significant role of adhesion properties of primary osteoblast-like cells in early adhesion events for chondroitin sulfate and dermatan sulfate surface molecules.

    Science.gov (United States)

    Stanford, C M; Solursh, M; Keller, J C

    1999-12-05

    The purpose of this study was to characterize the role of cell surface adhesive macromolecules through enzyme modulation and metabolic recovery prior to and during a kinetic cell adhesion assay. Primary rat calvarial osteoblast-like cells were derived from Sprague-Dawley calvarial plates. Cell adhesion kinetics was evaluated with the definition of first-order adhesion kinetics. Osteoblasts were incubated in an adhesion buffer for 1 h prior to a cell attachment assay using various enzymes to remove cell surface glycosaminoglycans (GAGs). A subtractive adhesion analysis was performed by plating cells at 5 x 10(4)/well for variable periods through 2 h. The medium was collected, the well surface washed and pooled, and the number of cells enumerated with a Coulter Counter. Cell adhesion demonstrated first-order logarithmic adhesion kinetics in the first 60 min. Scatchard analysis demonstrated a linear relationship. Preexposure of cells to various enzyme combinations demonstrated that 50% of the equilibrium adhesion was dependent on chondroitin sulfate or dermatan sulfate surface macromolecules. These results were confirmed with pretreatment with a metabolic inhibitor of GAG synthesis (beta-D-xyloside). These results suggest an important role for cell associated chondroitin sulfate and dermatan sulfate in cell adhesion in addition to Arg-Gly-Asp or integrin mediated adhesion events.

  2. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway.

    Science.gov (United States)

    Hsuan, Chin-Feng; Hsu, Hsia-Fen; Tseng, Wei-Kung; Lee, Thung-Lip; Wei, Yu-Feng; Hsu, Kwan-Lih; Wu, Chau-Chung; Houng, Jer-Yiing

    2015-09-17

    Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

  3. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Chin-Feng Hsuan

    2015-09-01

    Full Text Available Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut, luteolin-7-glucoside (lut-7-g, and oleanolic acid (OA on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs. The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB, an indicator of the activation of nuclear factor-kB (NF-kB. In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

  4. Effects of Ruan Jian San Jie decoction combined with simvastatintreatment on serum adhesion molecules, protease and endothelial indexes of carotid atherosclerosis patients

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yun Chen; Chun-Ying Chen; Hai-Bo Bai

    2015-01-01

    Objective: To study the effect of Ruan Jian San Jie decoction combined with simvastatin treatment on serum adhesion molecules, protease and endothelial indexes of carotid atherosclerosis patients. Methods: 100 carotid atherosclerosis patients found in health examination in our hospital from July 2013 to October 2014 were enrolled and randomly divided into two groups. Observation group received Ruan Jian San Jie decoction combined with simvastatin treatment; control group only received simvastatin treatment. Then serum adhesion molecules, protease contents and endothelial function indexes of both groups were detected. Results: (1) adhesion molecules: serum E-selectin, ICAM-1, VCAM-1, LFA-1, CD40 contents of observation group were lower than those of control group; (2) protease molecules: serum Cat K, MMP1, MMP2, MMP9 contents of observation group were lower than those of control group; TIMP1 content was higher than that of control group; (3) endothelial function: EMPs, carotid intima-media thickness and plaque area of observation group were lower than those of control group; FMD and vessel diameter were higher than those of control group. Conclusion: Ruan Jian San Jie decoction combined with simvastatin treatment is helpful to reduce the contents of serum adhesion molecules and protease molecules and improve endothelial function; it is an ideal method to treat carotid atherosclerosis.

  5. Novel secreted isoform of adhesion molecule ICAM-4: Potential regulator of membrane-associated ICAM-4 interactions

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    Lee, Gloria; Spring, Frances A.; Parons, Stephen F.; Mankelow, Tosti J.; Peters, Luanne L.; Koury, Mark J.; Mohandas, Narla; Anstee, David J.; Chasis, Joel Anne

    2003-02-18

    ICAM-4, a newly characterized adhesion molecule, is expressed early in human erythropoiesis and functions as a ligand for binding a4b1 and aV integrin-expressing cells. Within the bone marrow, erythroblasts surround central macrophages forming erythroblastic islands. Evidence suggests that these islands are highly specialized subcompartments where cell adhesion events, in concert with cytokines, play critical roles in regulating erythropoiesis and apoptosis. Since erythroblasts express a4b1 and ICAM-4 and macrophages exhibit aV, ICAM-4 is an attractive candidate for mediating cellular interactions within erythroblastic islands. To determine whether ICAM-4 binding properties are conserved across species, we first cloned and sequenced the murine homologue. The translated amino acid sequence showed 68 percent overall identity with human ICAM-4. Using recombinant murine ICAM-4 extracellular domains, we discovered that hematopoietic a4b1-expressing HEL cells and non-hematopoietic aV-expressing FLY cells adhered to mouse ICAM-4. Cell adhesion studies showed that FLY and HEL cells bound to mouse and human proteins with similar avidity. These data strongly suggest conservation of integrin-binding properties across species. Importantly, we characterized a novel second splice cDNA that would be predicted to encode an ICAM-4 isoform, lacking the membrane-spanning domain. Erythroblasts express both isoforms of ICAM-4. COS-7 cells transfected with GFP constructs of prototypic or novel ICAM-4 cDNA showed different cellular localization patterns. Moreover, analysis of tissue culture medium revealed that the novel ICAM-4 cDNA encodes a secreted protein. We postulate that secretion of this newly described isoform, ICAM-4S, may modulate binding of membrane-associated ICAM-4 and could thus play a critical regulatory role in erythroblast molecular attachments.

  6. Stroke Status Evoked Adhesion Molecule Genetic Alterations in Astrocytes Isolated from Stroke-Prone Spontaneously Hypertensive Rats and the Apigenin Inhibition of Their Expression

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    Kazuo Yamagata

    2010-01-01

    Full Text Available We examined the possibility that the expression of adhesion molecules is regulated differently in cultured astrocytes from stroke-prone spontaneously hypertensive rats (SHRSP/IZM rats than in those from Wistar Kyoto rats (WKY/IZM by tumor necrosis factor-alpha (TNF- or hypoxia and reoxygenation (H/R and the inhibitory effects of apigenin. It was found that the expression of vascular cell adhesion molecule-1 (VCAM-1 by TNF- in astrocytes isolated from SHRSP/IZM was increased compared with that in WKY/IZM. The expression of monocyte chemotactic protein-1 (MCP-1 mRNA induced by H/R in SHRSP/IZM astrocytes was increased compared with that in normal oxygen concentrations. Apigenin strongly attenuated TNF--induced VCAM-1 mRNA and protein expression and suppressed the adhesion of U937 cells and SHRSP/IZM astrocytes. These results suggest that the expression levels of adhesion molecules during H/R affect disease outcome and can drive SHRSP/IZM to stroke. It is suggested that apigenin regulates adhesion molecule expression in reactive astrocytes during ischemia.

  7. Sequential expression of adhesion and costimulatory molecules in graft-versus-host disease target organs after murine bone marrow transplantation across minor histocompatibility antigen barriers.

    Science.gov (United States)

    Eyrich, Matthias; Burger, Gudrun; Marquardt, Katja; Budach, Wilfried; Schilbach, Karin; Niethammer, Dietrich; Schlegel, Paul G

    2005-05-01

    Graft-versus-host disease (GVHD) is a potentially fatal complication after allogeneic bone marrow transplantation. However, few data exist thus far on the molecular signals governing leukocyte trafficking during the disease. We therefore investigated the sequential pattern of distinct adhesion, costimulatory, and apoptosis-related molecules in GVHD organs (ileum, colon, skin, and liver) after transplantation across minor histocompatibility barriers (B10.D2 --> BALB/c, both H-2d). To distinguish changes induced by the conditioning regimen from effects achieved by allogeneic cell transfer, syngeneic transplant recipients (BALB/c --> BALB/c) and irradiated nontransplanted mice were added as controls. Irradiation upregulated the expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-l, and B7-2 in ileum, as well as VCAM-1 and B7-2 in colon, on day 3 in all animals. Whereas in syngeneic mice these effects were reversed from day 9 on, allogeneic recipients showed further upregulation of VCAM-1, ICAM-1, B7-1, and B7-2 in these organs on day 22, when GVHD became clinically evident. Infiltration of CD4+ and CD8+ donor T cells was noted on day 9 in skin and liver and on day 22 in ileum and colon. Surprisingly, the expression of several other adhesion molecules, such as ICAM-2, platelet-endothelial cell adhesion molecule 1, E-selectin, and mucosal addressin cell adhesion molecule 1, did not change. Proapoptotic and antiapoptotic markers were balanced in GVHD organs with the exception of spleen, in which a preferential expression of the proapoptotic Bax could be noted. Our results indicate that irradiation-induced upregulation of VCAM-1, ICAM-1, and B7-2 provides early costimulatory signals to incoming donor T cells in the intestine, followed by a cascade of proinflammatory signals in other organs once the alloresponse is established.

  8. Adhesion molecules in Wilms tumor (part II : beta-catenin expression and significance

    Directory of Open Access Journals (Sweden)

    Basta-Jovanović Gordana M.

    2003-01-01

    Full Text Available Beta-catenin is a glicoprotein which has an important role in cell-cell adhesion, as well as in cell signal transmition, in u regulation of gen expression and in interaction with axin and APC (adenomatous poliposis coli. Its oncogenic role in several types of carcinomas in human population is well known. It is very likely that b-catenin as an protooncogen plays an importante role in genesis of Wilms tumor. It is well known that in 15% Wilms tumors there are b-catenin mutations, which indicates that there is a disorder in Wnt signal paththat plays an important role in Wilms tumor genesis. The aim of our study was to investigate b-catenin expression in Wilms tumor, to compaire it with the expression in normal renal tissue as well as to see if there is a positive correlation between b-catenin expression in Wilms tumor with tumor stage, histologic type and/ or prognostic group.

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

    Science.gov (United States)

    Park, Kyoung Ho; Yeo, Sang Won; Troy, Frederic A

    2014-10-17

    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. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  10. Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeable Haemophilus influenzae.

    Science.gov (United States)

    Novotny, Laura A; Bakaletz, Lauren O

    2016-08-01

    Nontypeable Haemophilus influenzae (NTHI) utilizes the Type IV pilus (Tfp) to adhere to respiratory tract epithelial cells thus colonizing its human host; however, the host cell receptor to which this adhesive protein binds is unknown. From a panel of receptors engaged by Tfp expressed by other bacterial species, we showed that the majority subunit of NTHI Tfp, PilA, bound to intercellular adhesion molecule 1 (ICAM1) and that this interaction was both specific and of high affinity. Further, Tfp-expressing NTHI inoculated on to polarized respiratory tract epithelial cells that expressed ICAM1 were significantly more adherent compared to Tfp-deficient NTHI or NTHI inoculated on to epithelial cells to which ICAM1 gene expression was silenced. Moreover, pre-incubation of epithelial cells with recombinant soluble PilA (rsPilA) blocked adherence of NTHI, an outcome that was abrogated by admixing rsPilA with ICAM1 prior to application on to the target cells. Epithelial cells infected with adenovirus or respiratory syncytial virus showed increased expression of ICAM1; this outcome supported augmented adherence of Tfp-expressing NTHI. Collectively, these data revealed the cognate receptor for NTHI Tfp as ICAM1 and promote continued development of a Tfp-targeted vaccine for NTHI-induced diseases of the airway wherein upper respiratory tract viruses play a key predisposing role.

  11. Neurite outgrowth induced by a synthetic peptide ligand of neural cell adhesion molecule requires fibroblast growth factor receptor activation

    DEFF Research Database (Denmark)

    Rønn, L C; Doherty, P; Holm, A;

    2000-01-01

    The neural cell adhesion molecule NCAM is involved in axonal outgrowth and target recognition in the developing nervous system. In vitro, NCAM-NCAM binding has been shown to induce neurite outgrowth, presumably through an activation of fibroblast growth factor receptors (FGFRs). We have recently...... identified a neuritogenic ligand, termed the C3 peptide, of the first immunoglobulin (lg) module of NCAM using a combinatorial library of synthetic peptides. Here we investigate whether stimulation of neurite outgrowth by this synthetic ligand of NCAM involves FGFRs. In primary cultures of cerebellar neurons...... from wild-type mice, the C3 peptide stimulated neurite outgrowth. This response was virtually absent in cultures of cerebellar neurons from transgenic mice expressing a dominant-negative form of the FGFR1. Likewise, in PC12E2 cells transiently expressing a dominant-negative form of the mouse FGFR1...

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    on granulocytes and improve clinical outcome. Sixteen patients undergoing open heart surgery participated in the study. Eight were randomized to receive methylprednisolone (30 mg/kg intravenously) at the start of anaesthesia while eight patients served as a control group. The oxidative burst was measured flow...... not improve the weaning from the ventilator or reduce the stay in the intensive-care unit. In conclusion, treatment with steroids prevented hyperthermia following open heart surgery with CPB and reduced capillary leak during ECC. Methylprednisolone, however, did not reduce the oxidative burst activity......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...

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

    Science.gov (United States)

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

    2009-01-06

    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. LTM formation also requires activity of the Notch cell-surface receptor. Although defects in Notch have been implicated in memory loss because of Alzheimer's disease, downstream signaling linking Notch to memory have not been determined. Strikingly, we found that Notch activity increases upon LTM induction and regulates Klg expression. Furthermore, Notch-induced enhancement of LTM is disrupted by a klg mutation. We propose that Klg is a downstream effector of Notch signaling that links Notch activity to memory.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    on granulocytes and improve clinical outcome. Sixteen patients undergoing open heart surgery participated in the study. Eight were randomized to receive methylprednisolone (30 mg/kg intravenously) at the start of anaesthesia while eight patients served as a control group. The oxidative burst was measured flow...... 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 did...... not improve the weaning from the ventilator or reduce the stay in the intensive-care unit. In conclusion, treatment with steroids prevented hyperthermia following open heart surgery with CPB and reduced capillary leak during ECC. Methylprednisolone, however, did not reduce the oxidative burst activity...

  16. Effects of Estrogen Level on the Function of Vascular Endothelial Cells and Expression of Vascular Cell Adhesion Molecule - 1φ

    Institute of Scientific and Technical Information of China (English)

    WU Saizhu(吴赛珠); LIU Jiangguo(刘建国); TAN Jiayu(谭家余); ZHoU Kexiang(周可祥); Gorge D Webb; WEI Heming(隗和明); GUO Zhiguang(郭志刚)

    2002-01-01

    Objectives To ob- serve the effect of different estrogen levels on the se- cretory function of vascular endothelial cells of female rats, and study the effect of modulation of estrogen level on the expression of vascular cell adhesion molecule - 1 and the concentration of estrogen receptorin vascular endothelial cells. Methods Radioim-munology was used to measure the serum concentrationof endothelin and PGI2, and copper-cadmium re-duction was employed to measure the serum content ofnitrogen monoxide. Radioligand binding and flowcy-tometry were used to measure the expression of estrogenreceptor and vascular cell adhesion molecule (VCAM-1 ) of vascular endothelial cells respectively. Re-sults 1. The serum concentration of nitric oxide andPGI2 decreased when the ovaries of female rats wereremoved. In ovariectomized rats, given estrogen, theconcentration rose ( P < 0.05), but the plasma con-centration of endothelin was adverse to it. 2. Theconcentration of estrogen receptor of vascular endothe-lial cells decreased remarkably when the ovaries of fe-male rats were removed. When given estrogen, it in-creased. 3. The percent of expressed VCAM - 1 in-creased siguificantly after interleukin- lβoperated onthe cells, but 17 - βestradiol at 3 × 10-8 ~ 10-6 mol/lall decreased the percent. Conclusions Estrogenlevel can influence the secretion of nitrogen monoxide,PGI2 and endothlin of vascular endothelial cells, andalso influence the concentration of estrogen receptor ofvascular endothelial cells. 17 -β Estradiol at 3 × 10-8~ 10-6 M can decrease the elevation of VCAM - 1 ofvascular endothelial cells induced by interleukin - 1 β.

  17. Pre-diagnostic levels of adiponectin and soluble vascular cell adhesion molecule-1 are associated with colorectal cancer risk

    Institute of Scientific and Technical Information of China (English)

    Mathilde Touvier; Pilar Galan; Sébastien Czernichow; Léopold Fezeu; Namanjeet Ahluwalia; Chantal Julia; Nathalie Charnaux; Angela Sutton; Caroline Méjean; Paule Latino-Martel; Serge Hercberg

    2012-01-01

    AIM:To examine the relationships between pre-diag-nostic biomarkers and colorectal cancer risk and assess their relevance in predictive models.METHODS:A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the SUpplementation en VItamines et Minéraux AntioXydants cohort in 1994 and the end of follow-up in 2007.Cases (n =50) were matched with two randomly selected controis (n =100).Conditional logistic regression models were used to investigate the associations between prediagnostic levels of hs-CRP,adiponectin,leptin,soluble vascular cell adhesion molecule-1 (sVCAM-1),soluble intercellular adhesion molecule-1,E-selectin,monocyte chemoattractant protein-1 and colorectal cancer risk.Area under the receiver operating curves (AUC) and relative integrated discrimination improvement (RIDI) statistics were used to assess the discriminatory poten tial of the models.RESULTS:Plasma adiponectin level was associated with decreased colorectal cancer risk (P for linear trend =0.03).Quartiles of sVCAM-1 were associated with increased colorectal cancer risk (P for linear trend =0.02).No association was observed with any of the other biomarkers.Compared to standard models with known risk factors,those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction (P for AUC improvement =0.01,RIDI =26.5%).CONCLUSION:These results suggest that pre-diagnostic plasma adiponectin and sVCAM-1 levels are associated with decreased and increased colorectal cancer risk,respectively.These relationships must be confirmed in large validation studies.

  18. Cell adhesion molecules P-cadherin and CD24 are markers for carcinoma and dysplasia in the biliary tract.

    Science.gov (United States)

    Riener, Marc-Oliver; Vogetseder, Alexander; Pestalozzi, Bernhard C; Clavien, Pierre-Alain; Probst-Hensch, Nicole; Kristiansen, Glen; Jochum, Wolfram

    2010-11-01

    P-cadherin (CDH3) and CD24 are cell adhesion molecules that control morphogenic processes, cell motility, and invasive growth of tumor cells. The aim of our study was to investigate P-cadherin and CD24 expression in carcinomas and dysplastic lesions of the biliary tract and to evaluate the potential diagnostic usefulness of these cell adhesion molecules. Using immunohistochemistry on tissue microarrays, we analyzed P-cadherin, CD24, and p53 expression in 117 carcinomas of the biliary tract (19 intrahepatic cholangiocarcinomas, 59 extrahepatic cholangiocarcinomas, and 39 gallbladder carcinomas) and correlated our findings with clinicopathologic parameters. We found P-cadherin positivity in 37% of intrahepatic cholangiocarcinomas, 73% of extrahepatic cholangiocarcinomas, and 64% of gallbladder carcinomas, respectively. CD24 reactivity was observed in 21% of intrahepatic cholangiocarcinomas, 58% of extrahepatic cholangiocarcinomas, and 42% of gallbladder carcinomas. Nuclear p53 expression was found in 37% of intrahepatic cholangiocarcinomas, 46% of extrahepatic cholangiocarcinomas, and 45% of gallbladder carcinomas. We also studied P-cadherin, CD24, and p53 expression in normal (n = 30), inflamed (n = 22), and dysplastic (n = 21) biliary epithelium of extrahepatic bile ducts. Dysplastic biliary epithelium was positive for P-cadherin in 91%, for CD24 in 71%, and for p53 in 24% of lesions, respectively. In contrast, normal and inflamed epithelia were negative for all 3 proteins. We conclude that P-cadherin and CD24 are expressed in carcinomas of the biliary tract with high frequency and at an early stage of carcinogenesis. Therefore, they may be useful markers for early detection and as targets for therapy of cholangiocarcinoma.

  19. Effect of Soy Nuts on Adhesion Molecules and Markers of Inflammation in Hypertensive and Normotensive Postmenopausal Women

    Science.gov (United States)

    Nasca, Melita M.; Zhou, Jin-Rong; Welty, Francine K.

    2011-01-01

    Recently, we showed that substituting soy nuts for non-soy protein in a therapeutic lifestyle change (TLC) diet lowered systolic and diastolic blood pressure 9.9% and 6.8%, respectively, in hypertensive postmenopausal women and 5.2% and 2.9%, respectively, in normotensive postmenopausal women. To examine mechanisms for these reductions, we measured markers of inflammation including soluble vascular cell adhesion molecule (sVCAM-1), soluble intercellular adhesion molecule (sICAM-1), C-reactive protein (CRP), interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9). Sixty healthy postmenopausal women (48 normotensive and 12 hypertensive) were randomized in a crossover design to a TLC diet alone or a TLC diet in which one-half cup soy nuts (25 g soy protein and 101 mg aglycone isoflavones) replaced 25 g of non-soy protein daily. Each diet was followed for 8 weeks. Compared to the TLC diet alone, levels of sVCAM-1 were significantly lower on the soy diet in hypertensive women (623.6±153.8 ng/ml versus 553.8±114.4 ng/ml, respectively, p=0.003) whereas no significant differences were observed in normotensive women. Soy nuts were associated with a trend toward reduction in CRP in normotensive women. No effect on levels of sICAM-1, IL-6 or MMP-9 was observed. In conclusion, the reduction in sVCAM-1 with soy nuts in hypertensive women suggests an improvement in endothelial function which may reflect an overall improvement in the underlying inflammatory process underlying atherosclerosis. PMID:18572041

  20. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.

    LENUS (Irish Health Repository)

    McSherry, Elaine A

    2012-02-01

    INTRODUCTION: The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration, and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. As cell migration is an early requirement for tumor metastasis, we sought to identify the JAM-A signalling events regulating migration in breast cancer cells. METHODS: MCF7 breast cancer cells (which express high endogenous levels of JAM-A) and primary cultures from breast cancer patients were used for this study. JAM-A was knocked down in MCF7 cells using siRNA to determine the consequences for cell adhesion, cell migration and the protein expression of various integrin subunits. As we had previously demonstrated a link between the expression of JAM-A and beta1-integrin, we examined activation of the beta1-integrin regulator Rap1 GTPase in response to JAM-A knockdown or functional antagonism. To test whether JAM-A, Rap1 and beta1-integrin lie in a linear pathway, we tested functional inhibitors of all three proteins separately or together in migration assays. Finally we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. RESULTS: JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to, and migration through, the beta1-integrin substrate fibronectin. This was accompanied by reduced protein expression of beta1-integrin and its binding partners alphaV- and alpha5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A, Rap1 and beta1-integrin, suggesting that they lie in a linear migratory pathway. Finally, in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation, we have demonstrated the formation of a complex between

  1. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.

    LENUS (Irish Health Repository)

    McSherry, Elaine A

    2011-03-23

    ABSTRACT: INTRODUCTION: The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration, and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. As cell migration is an early requirement for tumor metastasis, we sought to identify the JAM-A signalling events regulating migration in breast cancer cells. METHODS: MCF7 breast cancer cells (which express high endogenous levels of JAM-A) and primary cultures from breast cancer patients were used for this study. JAM-A was knocked down in MCF7 cells using siRNA to determine the consequences for cell adhesion, cell migration and the protein expression of various integrin subunits. As we had previously demonstrated a link between the expression of JAM-A and β1-integrin, we examined activation of the β1-integrin regulator Rap1 GTPase in response to JAM-A knockdown or functional antagonism. To test whether JAM-A, Rap1 and β1-integrin lie in a linear pathway, we tested functional inhibitors of all three proteins separately or together in migration assays. Finally we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. RESULTS: JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to, and migration through, the β1-integrin substrate fibronectin. This was accompanied by reduced protein expression of β1-integrin and its binding partners αV- and α5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A, Rap1 and β1-integrin, suggesting that they lie in a linear migratory pathway. Finally, in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation, we have demonstrated the formation of a complex between JAM-A, AF

  2. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase

    LENUS (Irish Health Repository)

    McSherry, Elaine A

    2011-03-23

    Abstract Introduction The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration, and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. As cell migration is an early requirement for tumor metastasis, we sought to identify the JAM-A signalling events regulating migration in breast cancer cells. Methods MCF7 breast cancer cells (which express high endogenous levels of JAM-A) and primary cultures from breast cancer patients were used for this study. JAM-A was knocked down in MCF7 cells using siRNA to determine the consequences for cell adhesion, cell migration and the protein expression of various integrin subunits. As we had previously demonstrated a link between the expression of JAM-A and β1-integrin, we examined activation of the β1-integrin regulator Rap1 GTPase in response to JAM-A knockdown or functional antagonism. To test whether JAM-A, Rap1 and β1-integrin lie in a linear pathway, we tested functional inhibitors of all three proteins separately or together in migration assays. Finally we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. Results JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to, and migration through, the β1-integrin substrate fibronectin. This was accompanied by reduced protein expression of β1-integrin and its binding partners αV- and α5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition, and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A, Rap1 and β1-integrin, suggesting that they lie in a linear migratory pathway. Finally, in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation, we have demonstrated the formation of a complex between JAM-A, AF-6

  3. Polymorphism K469E of intercellular adhesion molecule-1 gene and restenosis after coronary stenting in Chinese patients

    Institute of Scientific and Technical Information of China (English)

    刘兆平; 霍勇; 李建平; 张岩; 薛琳; 赵春玉; 洪秀梅; 黄爱群; 高炜

    2004-01-01

    Background Inflammation is a major cause of restenosis after coronary stenting. Intercellular adhesion molecule-1 ( ICAM-1 ) is an important adhesion molecule that plays a key role in the tight adhesion between leukocytes and vascular endothelium. The object of this study was to investigate the association between the K469E polymorphism of the ICAM-1 gene and restenosis after coronary stenting in North Chinese population.Methods The ICAM-1 K469E polymorphism was genotyped using polymerase chain reaction- restriction fragment length polymorphism method in 124 patients who had undergone coronary stenting and coronary angiography at least 3 months earlier. Information on clinical risk factors and procedure- related data were also collected. Results Of 124 enrolled patients in total, there were 72 cases of in-stent restenosis. The restenosis rate in this population was 58. 1%. The frequencies of the three possible genotypes of the ICAM-1 K469E polymorphism were: KK genotype 50.8%, EE genotype 41.9%, and EK genotype 41.9%.Among restenosis patients, the frequency of the KK genotype was 58. 3% and the frequency of E allele carriers was 41.7%. Among non-restenosis patients, the frequency of the KK genotype was 40.4%, and the frequency of E allele carriers was 59. 6%. The distribution of these two genotype groups between restenosis and non-restenosis patients was significantly different (P=0.049). Using multivariate logistic regression, the difference between the two groups was more apparent. The odds ratio of KK homozygotes vs E allele carriers was 2.6, with 95% confidence interval 1.2 -5.8 (P =0. 018). After grading of risk factors, we found that the KK genotype was a stronger predictor of in- stent restenosis in obesity or hyperlipemia patients, with an odds ratio of 9.3 and 3.7, respectively (P<0.05).Conclusion In our study population, KK homozygotes of the ICAM-1 codon 469 mutation had a higher risk of restenosis after coronary stenting, especially in the case of obese

  4. Small Molecules in C60 and C70: Which Complexes Could Be Stabilized?

    Science.gov (United States)

    Korona, Tatiana; Dodziuk, Helena

    2011-05-10

    The recent syntheses of complexes involving some small molecules in opened fullerenes and those of hydrogen molecule(s) in C60 and C70 are accompanied in the literature by numerous computations for endohedral fullerene complexes which cope with the problem of the stability of these complexes. In this contribution, stabilization energies of endohedral complexes of C60 and C70 with H2, N2, CO, HCN, H2O, H2S, NH3, CH4, CO2, C2H2, H2CO, and CH3OH guests have been estimated using symmetry-adapted perturbation theory, which, contrary to the standard DFT and some other approaches, correctly describes the dispersion contribution of the host-guest interactions. On the basis of these calculations, the endohedral complexes with all these guests were found stable in the larger fullerene, while the C60 cage was found too small to host the latter four molecules. Except for H2 and H2CO, a stabilization effect for most guests in the C60 cage is about 30 kJ/mol. For H2 and H2O guests, a typical supramolecular effect is observed; namely, the stabilization in the smaller cage is equal to or larger than that in the larger C70 host. Except for the water molecule where the induction interaction plays a non-negligible role, in all complexes the main stabilization effect comes from the dispersion interaction. The information on the stability of hypothetical endohedral fullerene complexes and physical factors contributing to it can be of importance in designing future experiments contributing to their applications.

  5. Opiates Upregulate Adhesion Molecule Expression in Brain MicroVascular Endothelial Cells (BMVEC: Implications for Altered Blood Brain Barrier (BBB Permeability

    Directory of Open Access Journals (Sweden)

    Madhavan P.N. Nair

    2006-01-01

    Full Text Available The blood-brain barrier (BBB is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of immunocompetent cells into the central nervous system (CNS. Expression of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 on brain microvascular endothelial cells (BMVEC and their interaction with human immunodeficiency virus (HIV-1 viral proteins may help enhance viral adhesion and virus-cell fusion resulting in increased infectivity. Additionally, transmigration through the BBB is facilitated by both endothelial and monocyte/macrophage-derived nitric oxide (NO. Dysregulated production of NO by BMVEC due to opiates and HIV-1 viral protein interactions play a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB. Opioids act as co-factors in the neuropathogenesis of HIV-1 by facilitating BBB dysfunction however, no studies have been done to investigate the role of opiates alone or in combination with HIV-1 viral proteins on adhesion molecule expression in BMVEC. We hypothesize that opiates such as heroin and morphine in conjunction with the HIV-1 viral protein gp120 increase the expression of adhesion molecules ICAM-1 and VCAM-1 and these effects are mediated via the modulation of NO. Results show that opiates alone and in synergy with gp120 increase both the genotypic and phenotypic expression of ICAM-1 and VCAM-1 by BMVEC, additionally, these opiate induced effects may be the result of increased NO production. These studies will provide a better understanding of how opiate abuse in conjunction with HIV-1 infection facilitates the breakdown of the BBB and exacerbates the neuropathogenesis of HIV-1. Elucidation of the mechanisms of BBB modulation will provide new therapeutic approaches to maintain BBB integrity

  6. Stability of organic molecules against shocks in the young Solar nebula

    NARCIS (Netherlands)

    Kamp, Inga; Milosavljevic, Milica; Stempels, E

    2009-01-01

    One of the fundamental astrobiology questions is how life has formed in our Solar System. In this context the formation and stability of abiotic organic molecules such as CH(4), formic acid and amino acids, is important for understanding how organic material has formed and survived shocks and energe

  7. Organising cells into tissues: new roles for cell adhesion molecules in planar cell polarity.

    Science.gov (United States)

    Saburi, Sakura; McNeill, Helen

    2005-10-01

    Planar cell polarity (PCP) is the coordinated organization of cells within the plane of the epithelium, first described in Drosophila. A Frizzled signalling pathway dedicated to PCP (the non-canonical Frizzled pathway) acts through Dishevelled and small G proteins, as does the classical Wnt pathway, but then diverges downstream of Dishevelled. Recent studies have demonstrated a crucial role for several atypical cadherin molecules (Fat, Dachsous and Flamingo) in controlling PCP signalling. Recent work has also indicated that the first sign of PCP during development is the polarized localization of PCP proteins (Frizzled, Flamingo, Dishevelled, etc). Exciting new data reveal that this PCP pathway is conserved to man.

  8. Assessment of the potential utility of different regions of Streptococcus uberis adhesion molecule (SUAM) for mastitis subunit vaccine development.

    Science.gov (United States)

    Perrig, Melina Soledad; Veaute, Carolina; Renna, María Sol; Pujato, Nazarena; Calvinho, Luis; Marcipar, Iván; Barbagelata, María Sol

    2017-04-01

    Streptococcus uberis is one of the most prevalent pathogens causing clinical and subclinical mastitis worldwide. Among bacterial factors involved in intramammary infections caused by this organism, S. uberis adhesion molecule (SUAM) is one of the main virulence factors identified. This molecule is involved in S. uberis internalization to mammary epithelial cells through lactoferrin (Lf) binding. The objective of this study was to evaluate SUAM properties as a potential subunit vaccine component for prevention of S. uberis mastitis. B epitope prediction analysis of SUAM sequence was used to identify potentially immunogenic regions. Since these regions were detected all along the gene, this criterion did not allow selecting a specific region as a potential immunogen. Hence, four fractions of SUAM (-1fr, 2fr, 3fr and 4fr), comprising most of the protein, were cloned and expressed. Every fraction elicited a humoral immune response in mice as predicted by bioinformatics analysis. SUAM-1fr generated antibodies with the highest recognition ability towards SUAM native protein. Moreover, antibodies against SUAM-1fr produced the highest proportion of internalization inhibition of S. uberis to mammary epithelial cells. In conclusion, SUAM immunogenic and functionally relevant regions were identified and allowed to propose SUAM-1fr as a potential candidate for a subunit vaccine for S. uberis mastitis prevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The glypiated neuronal cell adhesion molecule contactin/F11 complexes with src-family protein tyrosine kinase Fyn.

    Science.gov (United States)

    Zisch, A H; D'Alessandri, L; Amrein, K; Ranscht, B; Winterhalter, K H; Vaughan, L

    1995-06-01

    Glycosyl phosphatidylinositol-anchored glycoproteins of the immunoglobulin superfamily play an important role in the formation of neuronal networks during development. The mechanism whereby neuronal GPI-linked molecules transduce recognition signals remains to be established. Analysis of detergent-resistant immune-complexes reveals that the glypiated neuronal cell adhesion molecule contactin/F11 specifically complexes with the cytoplasmic, nonreceptor type src-family tyrosine kinase Fyn. Antibody-mediated cross-linking of contactin/F11 on embryonic chick neuronal cells leads to an increase of the Fyn-activity coprecipitated with contactin/F11, and elevates phosphorylation of an additional 75/80 K component within the contactin/F11-immune-complex. Additionally, binding of ligands, i.e., contactin/F11-specific antibody or tenascin-R, a natural ligand of contactin/F11, to the surface of HeLa transfectants expressing contactin/F11, causes capping of contactin/F11 and a concomitant change in the distribution of the intracellular kinase Fyn, thus confirming their physical association. This indicates that contactin/F11-mediated signaling requires Fyn.

  10. Expression of intercellular adhesion molecule-1 in UVA-irradiated human skin cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Treina, G.; Scaletta, C.; Frenk, E.; Applegate, L.A. [University Hospital-CHUV, Lausanne (Switzerland). Laboratory of Photobiology; Fourtanier, A.; Seite, S. [L`Oreal-Centre de Recherche Charles Zviak (France). Recherche Avancee Biologie

    1996-08-01

    Ultraviolet A (UVA) radiation represents an important oxidative stress to human skin and certain forms of oxidative stress have been shown to modulate intercellular adhesion molecule-1 (ICAM-1) expression. ICAM-1 has been shown to play an important part in many immune reactions and the perturbations of this molecule by ultraviolet radiation could have implications in many inflammatory responses. An enhancement immunohistochemical method with avidin/biotin was used for analysing the early effects of UVA radiation on human cell cultures and human skin (340-400 nm). Both in vitro and in vivo data show that ICAM-1 staining in epidermal keratinocytes, which was expressed constitutively, decreased in a UVA dose-dependent manner. The decrease was most noted at 3-6 h following UVA radiation with some ICAM-1 staining returning by 48 h post-UVA. ICAM-1 positive staining in the dermis was specific for vascular structures and was increased 24 h after UVA radiation. Cultured dermal fibroblasts exhibited ICAM-1 staining which increased slightly within 6-48 h post-UVA radiation. As epidermal ICAM-1 expression is depleted following UVA radiation and dermal expression increases due to an increase in the vascular structures, ICAM-1 provides a valuable marker following UVA radiation in human skin that can be readily measured in situ. (author).

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

    Institute of Scientific and Technical Information of China (English)

    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.

  12. NADPH OXIDASE AND LIPID RAFT-ASSOCIATED REDOX SIGNALING ARE REQUIRED FOR PCB153-INDUCED UPREGULATION OF CELL ADHESION MOLECULES IN HUMAN BRAIN ENDOTHELIAL CELLS

    Science.gov (United States)

    Eum, Sung Yong; Andras, Ibolya; Hennig, Bernhard; Toborek, Michal

    2009-01-01

    Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), can lead to chronic inflammation and the development of vascular diseases. Because cell adhesion molecules (CAMs) of the cerebrovascular endothelium regulate infiltration of inflammatory cells into the brain, we have explored the molecular mechanisms by which ortho-substituted polychlorinated biphenyls (PCBs), such as PCB153, can upregulate CAMs in brain endothelial cells. Exposure to PCB153 increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as elevated adhesion of leukocytes to brain endothelial cells. These effects were impeded by inhibitors of EGFR, JAKs, or Src activity. In addition, pharmacological inhibition of NADPH oxidase or disruption of lipid rafts by cholesterol depleting agents blocked PCB153-induced phosphorylation of JAK and Src kinases and upregulation of CAMs. In contrast, silencing of caveolin-1 by siRNA interference did not affect upregulation of ICAM-1 and VCAM-1 in brain endothelial cells stimulated by PCB153. Results of the present study indicate that lipid raft-dependent NADPH oxidase/JAK/EGFR signaling mechanisms regulate the expression of CAMs in brain endothelial cells and adhesion of leukocytes to endothelial monolayers. Due to its role in leukocyte infiltration, induction of CAMs may contribute to PCB-induced cerebrovascular disorders and neurotoxic effects in the CNS. PMID:19632255

  13. Prognostic impact of in vivo soluble cell adhesion molecules in metastatic renal cell carcinoma.

    Science.gov (United States)

    Hoffmann, R; Franzke, A; Buer, J; Sel, S; Oevermann, K; Duensing, A; Probst, M; Duensing, S; Kirchner, H; Ganser, A; Atzpodien, J

    1999-04-01

    The purpose of the study was to determine prognostic significance of pretreatment serum levels of different molecules involved in cell to cell interactions along with other clinical parameters in patients with metastatic renal cell carcinoma. sICAM-1, sVCAM-1 and sELAM-1 serum levels were determined by ELISA assays in sera from 99 patients with histologically confirmed progressive metastatic renal cell carcinoma prior to initiation of systemic therapy. Kaplan-Meier survival analysis, log-rank statistics and two-proportional Cox regression analyses were employed to identify risk factors and to demonstrate statistical independence. In univariate analyses, the following pretreatment risk factors could be identified: serum sICAM-1 level > 360 ng ml(-1), erythrocyte sedimentation rate > 70 mm h(-1), serum C-reactive protein level > 8 mg l(-1), serum lactic dehydrogenase level > 240 U/l and neutrophil count > 6000 microl(-1). Multivariate analyses demonstrated statistical independence for serum sICAM-1 level, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level as pretreatment predictors of overall patient survival. The prognostic significance of sICAM-1 might indicate a role of this molecule for tumour progression, potentially in association with the abrogation of anti-tumour immune responses. The possibility of defining a pretreatment risk model based on sICAM-1 level, ESR and CRP also warrants further investigation, with regard to a possible linkage between acute phase proteins and sICAM-1 levels.

  14. System of forest insect pheromone communication: stability of «information» molecules to environmental factors

    Directory of Open Access Journals (Sweden)

    V. G. Soukhovolsky

    2016-06-01

    Full Text Available Features of external environmental factors (such as electromagnetic radiation in certain spectral bands influencing pheromone molecules, which are carriers of information for forest insects in the search of the opposite sex, were examined. Stability of pheromone molecules for external influences has been studied for siberian moth Dendrolimus superans sibiricus Tschetv., pine moth Dendrilimus pini L., gypsy moth Lymantria dispar L., for xylophages Ips typographus L., Monochamus urussovi Fish. and Monochamus galloprovincialis Oliv. Properties of pheromone molecules were evaluated by calculations using quantum-chemical method B3LYP. Existing methods of quantum-chemical calculations are useful for analyzing the properties of quite small and uncomplicated molecules of forest insect pheromones. The calculations showed that the molecules of insect pheromones are able to absorb light in the ultraviolet range and move into an excited state. The values of dipole moments, the wavelengths of the absorption, atomic and molecular electronic properties of pheromones in the ground and excited states were calculated. The calculations showed that for the reaction of pheromones with oxygen an energy barrier is somewhat higher than for reactions of pheromones with water vapor. The worst reaction of pheromones with water molecules likely to pheromones such molecules whose dipole moment is comparable to the dipole moment of water. Quantum-chemical characteristics of the pheromone molecules can be linked to specific behavior of the insects.

  15. Small-molecule stabilization of the p53 - 14-3-3 protein-protein interaction.

    Science.gov (United States)

    Doveston, Richard G; Kuusk, Ave; Andrei, Sebastian A; Leysen, Seppe; Cao, Qing; Castaldi, Maria P; Hendricks, Adam; Brunsveld, Luc; Chen, Hongming; Boyd, Helen; Ottmann, Christian

    2017-08-01

    14-3-3 proteins are positive regulators of the tumor suppressor p53, the mutation of which is implicated in many human cancers. Current strategies for targeting of p53 involve restoration of wild-type function or inhibition of the interaction with MDM2, its key negative regulator. Despite the efficacy of these strategies, the alternate approach of stabilizing the interaction of p53 with positive regulators and, thus, enhancing tumor suppressor activity, has not been explored. Here, we report the first example of small-molecule stabilization of the 14-3-3 - p53 protein-protein interaction (PPI) and demonstrate the potential of this approach as a therapeutic modality. We also observed a disconnect between biophysical and crystallographic data in the presence of a stabilizing molecule, which is unusual in 14-3-3 PPIs. © 2017 Federation of European Biochemical Societies.

  16. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

    Science.gov (United States)

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (Pdrug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

  17. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

    Science.gov (United States)

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829

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

    DEFF Research Database (Denmark)

    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...

  19. Expression of neural cell adhesion molecules and neurofilament protein isoforms in Ewing's sarcoma of bone and soft tissue sarcomas of other than rhabdomyosarcoma

    NARCIS (Netherlands)

    Molenaar, W.M.; Muntinghe, F.L.H.

    1999-01-01

    In a previous study, it was shown that rhabdomyosarcomas widely express "neural" markers, such as neural cell adhesion molecules (N-CAM) and neurofilament protein isoforms, In the current study, a series of Ewing's sarcomas of bone and soft tissue sarcomas other than rhabdomyosarcoma was probed for

  20. Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Li, Shizhong; Hinsby, Anders Mørkeberg

    2008-01-01

    The neuronal cell adhesion molecule (CAM) L1 promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). The present study demonstrates a direct interaction between L1 fibronectin type III (FN3) modules I-V and FGFR1 immunoglobulin (Ig) modules ...

  1. A peptide motif from the second fibronectin module of the neural cell adhesion molecule, NCAM, NLIKQDDGGSPIRHY, is a binding site for the FGF receptor

    DEFF Research Database (Denmark)

    Jacobsen, Jacob Hedemand; Kiselyov, Vladislav; Bock, Elisabeth

    2008-01-01

    The mechanism of fibroblast growth factor receptor (FGFR) activation by the neural cell adhesion molecule (NCAM) is not well understood. A motif in the second NCAM fibronectin type III (FN3) module, termed FGL, has by means of nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) a...

  2. The fibroblast growth factor receptor acid box is essential for interactions with N-cadherin and all of the major isoforms of neural cell adhesion molecule.

    Science.gov (United States)

    Sanchez-Heras, Elena; Howell, Fiona V; Williams, Gareth; Doherty, Patrick

    2006-11-17

    Interactions between the neural cell adhesion molecules NCAM and N-cadherin with the fibroblast growth factor receptor (FGFR) are important for a number of developmental events and have also been implicated in tumor progression. The factors regulating these interactions are not known. We have used co-immunoprecipitation and co-clustering paradigms to show that both adhesion molecules can interact with the 3Ig IIIC isoform of the FGFR1 in a number of cell types. Interestingly, whereas the interaction can be seen over most of the cell surface, it is not seen at points of cell-cell contact where the adhesion molecules accumulate at stable junctions. We also demonstrate for the first time that all of the major isoforms of NCAM can interact with the FGFR. Using deletion mutagenesis we have found that the adhesion molecule/FGFR interaction can withstand the removal of most of any one of the FGFR immunoglobulin-like domains (D1-D3). In contrast, the FGFR interaction with N-cadherin and NCAM (but not FGF) is absolutely dependant on the presence of the acid box motif that can be found in the linker region between D1 and D2. As this motif can be spliced out of all four FGFRs, it suggests that this is one mechanism that can regulate the interaction of the receptor with different ligand classes.

  3. Soluble intercellular adhesion molecule 1 and flow-mediated dilatation are related to the estimated risk of coronary heart disease independently from each other

    NARCIS (Netherlands)

    Witte, D.R.; Broekmans, W.M.R.; Kardinaal, A.F.M.; Klöpping-Ketelaars, I.A.A.; Poppel, G. van; Bots, M.L.; Kluft, C.; Princen, J.M.G.

    2003-01-01

    Background: Flow mediated dilatation (FMD) of the brachial artery and soluble intercellular adhesion molecule 1 (sICAM-1) are measures of distinct functions of the endothelium, reflecting nitric oxide (NO)-mediated and pro-inflammatory status, respectively. The comparative value of the two measures

  4. Targeted DNA Methylation by a DNA Methyltransferase Coupled to a Triple Helix Forming Oligonucleotide To Down-Regulate the Epithelial Cell Adhesion Molecule

    NARCIS (Netherlands)

    van der Gun, Bernardina T. F.; Maluszynska-Hoffman, Maria; Kiss, Antal; Arendzen, Alice J.; Ruiters, Marcel H. J.; McLaughlin, Pamela M. J.; Weinhold, Elmar; Rots, Marianne G.

    2010-01-01

    The epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein that has been identified as a marker of cancer-initiating cells. EpCAM is highly expressed on most carcinomas, and transient silencing of EpCAM expression leads to reduced oncogenic potential. To silence (he EpCAM gene in a per

  5. Levels of soluble intercellular adhesion molecule 1, eicosanoids and cytokines in ascites of patients with liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis

    NARCIS (Netherlands)

    W.M. Pruimboom (Wanda); D.J. Bac (Dirk Jan); A.P.J. van Dijk (Arie); I.M. Garrelds (Ingrid); C.J.A.M. Tak (Corné); I.L. Bonta; J.H.P. Wilson (Paul); F.J. Zijlstra (Freek)

    1995-01-01

    textabstractThe levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1β, interleukin-6 and tumour necrosis factor-α and soluble intercellular adhesion molecule 1 were measured in ascites and plasma samples of patients with liver

  6. Family with sequence similarity 5, member C (FAM5C increases leukocyte adhesion molecules in vascular endothelial cells: implication in vascular inflammation.

    Directory of Open Access Journals (Sweden)

    Junya Sato

    Full Text Available Identification of the regulators of vascular inflammation is important if we are to understand the molecular mechanisms leading to atherosclerosis and consequent ischemic heart disease, including acute myocardial infarction. Gene polymorphisms in family with sequence similarity 5, member C (FAM5C are associated with an increased risk of acute myocardial infarction, but little is known about the function of this gene product in blood vessels. Here, we report that the regulation of the expression and function of FAM5C in endothelial cells. We show here that FAM5C is expressed in endothelial cells in vitro and in vivo. Immunofluorescence microscopy showed localization of FAM5C in the Golgi in cultured human endothelial cells. Immunohistochemistry on serial sections of human coronary artery showed that FAM5C-positive endothelium expressed intercellular adhesion molecule-1 (ICAM-1 or vascular cell adhesion molecule-1 (VCAM-1. In cultured human endothelial cells, the overexpression of FAM5C increased the reactive oxygen species (ROS production, nuclear factor-κB (NF-κB activity and the expression of ICAM-1, VCAM-1 and E-selectin mRNAs, resulting in enhanced monocyte adhesion. FAM5C was upregulated in response to inflammatory stimuli, such as TNF-α, in an NF-κB- and JNK-dependent manner. Knockdown of FAM5C by small interfering RNA inhibited the increase in the TNF-α-induced production of ROS, NF-κB activity and expression of these leukocyte adhesion molecule mRNAs, resulting in reduced monocyte adhesion. These results suggest that in endothelial cells, when FAM5C is upregulated in response to inflammatory stimuli, it increases the expression of leukocyte adhesion molecules by increasing ROS production and NF-κB activity.

  7. Changes in serum cellular adhesion molecule and matrix metalloproteinase-9 levels in patients with cerebral infarction following hyperbaric oxygen therapy A case and intergroup control study

    Institute of Scientific and Technical Information of China (English)

    Renliang Zhao; Chunxia Wang; Yongjun Wang

    2008-01-01

    BACKGROUND: Animal studies have confirmed that hyperbaric oxygen (HBO) therapy can reduce matrix metalloproteinase activity and blood brain barrier permeability, thereby exhibiting neuroprotective effects. However, at present, consensus does not exist in terms of its clinical efficacy. OBJECTIVE: To validate the significance of changes in serum cellular adhesion molecule and MMP-9 levels in patients with cerebral infarction following HBO therapy. DESIGN, TIME AND SETTING: This randomized, controlled, neurobiochemical study was performed at the Department of Neurology, Affiliated Hospital of Qingdao University Medical College between December 2002 and March 2006. PARTICIPANTS: A total of 112 patients with acute cerebral infarction of internal carotid artery, comprising 64 males and 48 females, averaging (67 ± 11) years, were recruited and randomized to a HBO group (n = 50) and a routine treatment group (n = 62). An additional 30 gender- and age-matched normal subjects, consisting of 17 males and 13 females, averaging (63 ± 9) years, were enrolled as control subjects. METHODS: The routine treatment group received routine drug treatment and rehabilitation exercise. HBO treatment was additionally performed in the HBO group, once a day, for a total of 10 days. MAIN OUTCOME MEASURES: Serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were detected by enzyme linked immunosorbent assay. RESULTS: Upon admission, serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were significantly increased in patients with cerebral infarction, compared with control subjects (P < 0.01). Following HBO and routine treatments, serum levels of the above-mentioned indices were significantly reduced in the HBO and routine treatment groups (P < 0.01). Moreover, greater efficacy was observed in the HBO

  8. IL-17A and TNF-α Increase the Expression of the Antiapoptotic Adhesion Molecule Amigo-2 in Arthritis Synoviocytes

    Science.gov (United States)

    Benedetti, Giulia; Bonaventura, Paola; Lavocat, Fabien; Miossec, Pierre

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disorder, characterized by a persistent immune cell infiltrate in the synovium accompanied by high levels of inflammatory mediators and synovial hyperplasia. Despite significant therapeutic advances, RA remains an important unmet medical need. To discover potential new genes controlling inflammation and apoptosis in synoviocytes, genes induced by the two pro-inflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 17A (IL-17A), were systematically searched. We identified Amphoterin-induced gene and ORF 2 (Amigo-2), a novel antiapoptotic adhesion molecule, as synergistically upregulated by the IL-17A/TNF combination specifically in RA synoviocytes. In addition, when RA synoviocytes were cocultured with immune cells, Amigo2 expression was significantly increased in both fibroblasts and immune cells. This induction persisted in RA synoviocytes even after the removal of the immune cells. Amigo2 induction was ERK-dependent and on the contrary, inhibited by JNK. Furthermore, Amigo2 expression levels correlated with apoptosis of the cells when exposed to the proapoptotic agent cadmium (Cd). Interestingly, exposure of the cells to HMGB1 in inflammatory conditions increased synergistically Amigo2 expression and significantly reduced Cd-mediated cellular toxicity. Our findings support a model whereby cell–cell contact with immune cells and exposure to the combination of both inflammatory cytokines and HMGB1 in the joints of RA patients increases Amigo2 expression in synoviocytes in an ERK-dependent manner which, in turn, enhances cellular adhesion and promotes cell survival and cellular proliferation. PMID:27446084

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Effect of thermal shock loadings on stability of dentin-composite polymer material adhesive interfaces

    Science.gov (United States)

    Bessudnova, Nadezda O.; Shlyapnikova, Olga A.; Venig, Sergey B.; Gribov, Andrey N.

    2015-03-01

    In the past several decades the problem of longevity and durability of adhesive interfaces between hard tooth tissues and composite resin-based materials are of great interest among dental researchers and clinicians. These parameters are partially determined by adhesive system mechanical properties. In the present research project nanoindentation has been examined to test hardness of dental adhesive systems. A series of laboratory experiments was performed to study the effect of light curing time and oxygen inhibition phenomenon on light-cured adhesive material hardness. An adhesive system AdperTM Single Bond (3M ESPE) was selected as a material for testing. The analysis of experimental data revealed that the maximum values of hardness were observed after the material had been light-cured for 20 seconds, as outlined in guidelines for polymerization time of the adhesive system. The experimental studies of oxygen inhibition influence on adhesive system hardness pointed out to the fact that the dispersive layer removal led to increase in adhesive system hardness. A long - time exposure of polymerized material of adhesive system at open air at room temperature resulted in no changes in its hardness, which was likely to be determined by the mutual effect of rival processes of air oxygen inhibition and directed light curing.

  11. The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion.

    LENUS (Irish Health Repository)

    Lan, W

    2012-02-03

    BACKGROUND: Changes in neutrophil and endothelial adhesion molecule expression occur during perioperative ischaemia and reperfusion (I\\/R) injury. We investigated the effects of lidocaine on neutrophil-independent changes in neutrophil and endothelial adhesion molecule expression associated with tourniquet-induced I\\/R. METHODS: Plasma was obtained from venous blood samples (tourniquet arm) taken before (baseline), during, 15 min, 2 and 24 h following tourniquet release in seven patients undergoing elective upper limb surgery with tourniquet application. Isolated neutrophils from healthy volunteers (n = 7) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1) for 1 h, and then incubated with I\\/R plasma for 2 h. Human umbilical vein endothelial cells (HUVECs) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)) for 1 h, and then incubated with the plasma for 4 h. Adhesion molecule expression was estimated using flow cytometry. Data were analysed using ANOVA and post hoc Student-Newman-Keuls tests. RESULTS: I\\/R plasma (withdrawn 15 min following tourniquet release) increased isolated neutrophil CD11b (P = 0.03), CD18 (P = 0.01) and endothelial intercellular adhesion molecule-1 (ICAM-1) (P = 0.008) expression compared to baseline. CD11b, CD18 and ICAM-1 expression on lidocaine (0.005 mg mL(-1)) treated neutrophils was similar to control. CD11b (P < 0.001), CD18 (P = 0.03) and ICAM-1 (P = 0.002) expression on lidocaine (0.05 mg mL(-1)) treated neutrophils and HUVECs was less than that on controls. CONCLUSION: Increased in vitro neutrophil and endothelial cell adhesion molecule expression on exposure to plasma obtained during the early reperfusion phase is diminished by lidocaine at greater than clinically relevant plasma concentrations.

  12. Platelet Endothelial Cell Adhesion Molecule-1 Gene Polymorphisms are Associated with Coronary Artery Lesions in the Chronic Stage of Kawasaki Disease.

    Science.gov (United States)

    Lu, Wen-Hsien; Huang, Sin-Jhih; Yuh, Yeong-Seng; Hsieh, Kai-Sheng; Tang, Chia-Wan; Liou, Huei-Han; Ger, Luo-Ping

    2017-05-01

    Kawasaki disease is the most common cause of pediatric acquired heart disease. The role of platelet endothelial cell adhesion molecule-1 in the inflammatory process has been documented. To date, no report has investigated the relationship between coronary artery lesions of Kawasaki disease and platelet endothelial cell adhesion molecule-1 polymorphisms. A total of 114 Kawasaki disease children with coronary artery lesions and 185 Kawasaki disease children without coronary artery lesions were recruited in this study. The TaqMan assay was conducted to identify the genotype in this case-control study. In three single nucleotide polymorphisms (Leu125Val, Ser563Asn, and Arg670Gly) of platelet endothelial cell adhesion molecule-1, we found that the Leu-Ser-Arg haplotype was associated with a significantly increased risk for coronary artery lesions in the chronic stage (odds ratio 3.05, 95% confidence interval 1.06-8.80, p = 0.039), but not for coronary artery lesions in the acute stage. Analysis based on the diplotypes of platelet endothelial cell adhesion molecule-1 also showed that Kawasaki disease with one or two alleles of Leu-Ser-Arg had a significantly increased risk of chronic coronary artery lesions (odds ratio 3.38, 95% confidence interval 1.11-10.28, p = 0.032) and had increased platelet counts after Kawasaki disease was diagnosed, as compared to those with other diplotypes. The haplotype of platelet endothelial cell adhesion molecule-1 Leu-Ser-Arg might be associated with the increased platelet counts and the following risk of chronic coronary artery lesions in a dominant manner in Kawasaki disease.

  13. Adhesion molecules involved in neutrophil recruitment during sepsis-induced acute kidney injury.

    Science.gov (United States)

    Herter, Jan M; Rossaint, Jan; Spieker, Tilmann; Zarbock, Alexander

    2014-01-01

    Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with high mortality. Recruitment of neutrophils is a hallmark in the pathogenesis of AKI. Although ischemia-reperfusion injury (IRI) is a frequently used research model of AKI, the clinical relevance of IRI-induced AKI is limited. Epidemiologically, sepsis is the prevailing cause of kidney injury. However, it is still unknown whether these distinct entities of AKI share the same pathophysiological mechanisms. This study was initiated to investigate the molecular mechanisms of neutrophil recruitment into the kidney in a murine model of sepsis-induced AKI. By using a flow cytometry-based method, we show that the two β2-integrins Mac-1 and LFA-1 as well as E-selectin and P-selectin are involved in neutrophil recruitment into the kidney after induction of sepsis. The molecular mechanisms of neutrophil recruitment were further investigated using intravital microscopy, demonstrating that blocking one of these four molecules reduces the number of adherent leukocytes. This was accompanied by a renal upregulation of E-selectin, P-selectin and ICAM-1 (the counter-receptor of β2-integrins on endothelial cells) after sepsis induction. We conclude that blocking P-selectin, E-selectin, Mac-1 or LFA-1 protects mice from sepsis-induced AKI.

  14. A novel DBL-domain of the P. falciparum 332 molecule possibly involved in erythrocyte adhesion.

    Directory of Open Access Journals (Sweden)

    Kirsten Moll

    Full Text Available Plasmodium falciparum malaria is brought about by the asexual stages of the parasite residing in human red blood cells (RBC. Contact between the erythrocyte surface and the merozoite is the first step for successful invasion and proliferation of the parasite. A number of different pathways utilised by the parasite to adhere and invade the host RBC have been characterized, but the complete biology of this process remains elusive. We here report the identification of an open reading frame (ORF representing a hitherto unknown second exon of the Pf332 gene that encodes a cysteine-rich polypeptide with a high degree of similarity to the Duffy-binding-like (DBL domain of the erythrocyte-binding-ligand (EBL family. The sequence of this DBL-domain is conserved and expressed in all parasite clones/strains investigated. In addition, the expression level of Pf332 correlates with proliferation efficiency of the parasites in vitro. Antibodies raised against the DBL-domain are able to reduce the invasion efficiency of different parasite clones/strains. Analysis of the DBL-domain revealed its ability to bind to uninfected human RBC, and moreover demonstrated association with the iRBC surface. Thus, Pf332 is a molecule with a potential role to support merozoite invasion. Due to the high level of conservation in sequence, the novel DBL-domain of Pf332 is of possible importance for development of novel anti-malaria drugs and vaccines.

  15. Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells.

    Science.gov (United States)

    Sosnovtsev, Stanislav V; Sandoval-Jaime, Carlos; Parra, Gabriel I; Tin, Christine M; Jones, Ronald W; Soden, Jo; Barnes, Donna; Freeth, Jim; Smith, Alvin W; Green, Kim Y

    2017-02-14

    The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.IMPORTANCE Vesiviruses, such as San Miguel sea lion virus and feline calicivirus, are typically associated with infection in animal hosts. Following the accidental infection of a laboratory worker with San Miguel sea lion virus, a related virus was isolated in cell culture and named Hom-1. In this study, we found that Hom-1 could be propagated in a number of human cell lines, making it the first calicivirus to replicate efficiently in cultured human cells. Screening of a library of human cell surface membrane proteins showed that the virus could utilize human junctional adhesion molecule 1 as a receptor to enter cells and initiate replication. The Hom-1 virus presents a new

  16. FMC46, a cell protrusion-associated leukocyte adhesion molecule-1 epitope on human lymphocytes and thymocytes.

    Science.gov (United States)

    Pilarski, L M; Turley, E A; Shaw, A R; Gallatin, W M; Laderoute, M P; Gillitzer, R; Beckman, I G; Zola, H

    1991-07-01

    In this report, we describe a 76-kDa glycoprotein recognized by mAb FMC46 that, by virtue of its concentration on cell protrusions involved in motility, may be important in lymphoid cell locomotion. FMC46 detects an epitope of the leukocyte adhesion molecule-1 (LAM-1), a member of the selecting family (LAM-1, Endothelial Leukocyte Adhesion Molecular-1 (ELAM-1), and Granule Membrane Protein-140 (GMP-140), that is expressed on LAM-1-transfected cell lines, is a glycosylation epitope based on its loss after culture in tunicamycin, and is closely related to the LAM-1.2 epitope. FMC46 is expressed at high density on the majority of CD45RA+ and CD45RO+ peripheral blood T cells (60 to 70%) and on a subset of thymocytes that includes the multinegative CD3- CD4- CD8- progenitor cells (100% FMC46hi) and the CD45R0- presumptive thymic generative lineage (70% FMC46hi). It appears at reduced density and frequency on CD45RA- thymocytes (50% FMC46lo), comprised mainly of death-committed thymocytes. Among thymic subsets defined by expression of CD4 and/or CD8, FMC46 is expressed at high density predominantly on a subset of single-positive cells and not on double-positive cells. These results suggest a fundamental role for LAM-1 in thymic development, with a high density preferentially expressed on cells involved in thymic generative processes and a low density on cells progressing to intrathymic death. A major subset of peripheral blood B cells and thymic B cells also express FMC46. Immunohistochemistry on frozen sections indicated strong staining in splenic follicles and around blood vessels, staining of the thymic medulla and subcapsular areas, and staining of the mantle zone of germinal centers of the lymph node. FMC46+ lymphocytes accumulated along high endothelial venules in the lymph node. On locomoting multinegative thymocytes, FMC46 is concentrated on the leading tip of extended processes, on pseudopods, and on ruffles, unlike the distribution of either CD44 or TQ1 (LAM 1

  17. Manassantin A and B isolated from Saururus chinensis inhibit TNF-alpha-induced cell adhesion molecule expression of human umbilical vein endothelial cells.

    Science.gov (United States)

    Kwon, Oh Eok; Lee, Hyun Sun; Lee, Seung Woong; Chung, Mi Yeon; Bae, Ki Hwan; Rho, Mun-Chual; Kim, Young-Kook

    2005-01-01

    Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.

  18. Protein stability in stored decellularized heart valve scaffolds and diffusion kinetics of protective molecules.

    Science.gov (United States)

    Wang, Shangping; Oldenhof, Harriëtte; Dai, Xiaolei; Haverich, Axel; Hilfiker, Andres; Harder, Michael; Wolkers, Willem F

    2014-02-01

    Decellularized tissues can be used as matrix implants. The aims of this study were to investigate protein stability and solvent accessibility in decellularized pulmonary heart valve tissues. Protein denaturation profiles of tissues were studied by differential scanning calorimetry. Protein solvent accessibility of tissue exposed to D2O, and diffusion kinetics of various protective molecules were studied by Fourier transform infrared spectroscopy. Little changes were observed in the protein denaturation temperature during storage, at either 5 or 40°C. Glycerol was found to stabilize proteins; it increased the protein denaturation temperature. The stabilizing effect of glycerol disappeared after washing the sample with saline solution. Hydrogen-to-deuterium exchange rates of protein amide groups were fastest in leaflet tissue, followed by artery and muscle tissue. Diffusion of glycerol was found to be fastest in muscle tissue, followed by artery and leaflet tissue. Diffusion coefficients were derived and used to estimate the time needed to reach saturation. Fixation of tissue with glutaraldehyde had little effects on exchange and diffusion rates. Diffusion rates decreased with increasing molecular size. Proteins in decellularized heart valve tissue are stable during storage. Glycerol increases protein stability in a reversible manner. Solvent accessibility studies of protein amide groups provide an additional tool to study proteins in tissues. Diffusion coefficients can be derived to simulate diffusion kinetics of protective molecules in tissues. This study provides novel tools to evaluate protein stability and solvent accessibility in tissues, which can be used to develop biopreservation strategies.

  19. Endothelium adhesion molecules ICAM-1, ICAM-2, VCAM-1 and VLA-4 expression in leprosy.

    Science.gov (United States)

    de Sousa, Juarez; Sousa Aarão, Tinara Leila; Rodrigues de Sousa, Jorge; Hirai, Kelly Emi; Silva, Luciana Mota; Dias, Leonidas Braga; Oliveira Carneiro, Francisca Regina; Fuzii, Hellen Thais; Quaresma, Juarez Antonio Simões

    2017-03-01

    Leprosy triggers a complex relationship between the pathogen and host immune response. Endothelium plays an important role in this immune response by directly influencing cell migration to infected tissues. The objective of this work is to investigate the possible role of endothelium in M. leprae infection, correlating the characteristics of endothelial markers with the expression pattern of cytokines. Thirty-six skin biopsy samples were cut into 5-μm thick sections and stained with hematoxylin-eosin and Ziehl-Neelsen for morphological analysis and then submitted to immunohistochemical analysis using monoclonal antibodies against ICAM-1, ICAM-2, VCAM-1, and VLA-4. Immunostaining for ICAM-1 showed a significantly larger number of stained endothelial cells in the tuberculoid leprosy (9.92 ± 1.11 cells/mm(2)) when compared to lepromatous samples (5.87 ± 1.01 cells/mm(2)) and ICAM-2 revealed no significant difference in the number of endothelial cells expressing this marker between the tuberculoid (13.21 ± 1.27 cells/mm(2)) and lepromatous leprosy (14.3 ± 1.02 cells/mm(2)). VCAM-1-immunostained showed 18.28 ± 1.46/mm(2) cells in tuberculoid leprosy and 10.67 ± 1.25 cells/mm(2) in the lepromatous leprosy. VLA-4 exhibited 22.46 ± 1.38 cells/mm(2) in the tuberculoid leprosy 16.04 ± 1.56 cells/mm(2) in the lepromatous leprosy. Samples with characteristics of the tuberculoid leprosy exhibited a larger number of cells stained with ICAM-1, VCAM-1 and VLA-4, demonstrating the importance of these molecules in the migration and selection of cells that reach the inflamed tissue. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Dual Function Additives: A Small Molecule Crosslinker for Enhanced Efficiency and Stability in Organic Solar Cells

    KAUST Repository

    Rumer, Joseph W.

    2015-02-01

    A bis-azide-based small molecule crosslinker is synthesized and evaluated as both a stabilizing and efficiency-boosting additive in bulk heterojunction organic photovoltaic cells. Activated by a noninvasive and scalable solution processing technique, polymer:fullerene blends exhibit improved thermal stability with suppressed polymer skin formation at the cathode and frustrated fullerene aggregation on ageing, with initial efficiency increased from 6% to 7%. © 2015 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Streptococcus pyogenes Phospholipase A2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice

    Directory of Open Access Journals (Sweden)

    Masataka Oda

    2017-06-01

    Full Text Available The Streptococcus pyogenes phospholipase A2 (SlaA gene is highly conserved in the M3 serotype of group A S. pyogenes, which often involves hypervirulent clones. However, the role of SlaA in S. pyogenes pathogenesis is unclear. Herein, we report that SlaA induces the expression of intercellular adhesion molecule 1 (ICAM1 and vascular cell adhesion molecule 1 (VCAM1 via the arachidonic acid signaling cascade. Notably, recombinant SlaA induced ICAM1 and VCAM1 expression in human umbilical vein endothelial cells (HUVECs, resulting in enhanced adhesion of human monocytic leukemia (THP-1 cells. However, C134A, a variant enzyme with no enzymatic activity, did not induce such events. In addition, culture supernatants from S. pyogenes SSI-1 enhanced the adhesion of THP-1 cells to HUVECs, but culture supernatants from the ΔslaA isogenic mutant strain had limited effects. Aspirin, a cyclooxygenase 2 inhibitor, prevented the adhesion of THP-1 cells to HUVECs and did not induce ICAM1 and VCAM1 expression in HUVECs treated with SlaA. However, zileuton, a 5-lipoxygenase inhibitor, did not exhibit such effects. Furthermore, pre-administration of aspirin in mice intravenously injected with SlaA attenuated the transcriptional abundance of ICAM1 and VCAM1 in the aorta. These results suggested that SlaA from S. pyogenes stimulates the expression of adhesion molecules in vascular endothelial cells. Thus, SlaA contributes to the inflammation of vascular endothelial cells upon S. pyogenes infection.

  2. The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-κB Pathway.

    Science.gov (United States)

    Hsueh, Tun-Pin; Sheen, Jer-Ming; Pang, Jong-Hwei S; Bi, Kuo-Wei; Huang, Chao-Chun; Wu, Hsiao-Ting; Huang, Sheng-Teng

    2016-02-05

    Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated HUVECs. The TNF-α-induced expressions of cell adhesion molecules, including VCAM-1, ICAM-1 and E-selectin, at both the mRNA and protein levels, were significantly suppressed by naringin in a dose dependent manner. In addition, the TNF-α-induced mRNA and protein levels of chemokines, including fractalkine/CX3CL1, MCP-1 and RANTES, were also reduced by naringin. Naringin significantly inhibited TNF-α-induced nuclear translocation of NF-κB, which resulted from the inhibited phosphorylation of IKKα/β, IκB-α and NF-κB. Altogether, we proposed that naringin modulated TNF-α-induced expressions of cell adhesion molecules and chemokines through the inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway to exert the anti-atherosclerotic effect.

  3. 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

    DEFF Research Database (Denmark)

    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...... not require NCAM-mediated fibroblast growth factor receptor activation....... on axon guidance in Drosophila suggest that NCAM also regulates the epidermal growth factor receptor (EGFR) (Molecular and Cellular Neuroscience, 28, 2005, 141). A possible interaction between NCAM and EGFR in mammalian cells has not been investigated. The present study demonstrates for the first time...

  4. Glycosylation specific for adhesion molecules in epidermis and its receptor revealed by glycoform-focused reverse genomics.

    Science.gov (United States)

    Uematsu, Rie; Shinohara, Yasuro; Nakagawa, Hiroaki; Kurogochi, Masaki; Furukawa, Jun-ichi; Miura, Yoshiaki; Akiyama, Masashi; Shimizu, Hiroshi; Nishimura, Shin-ichiro

    2009-02-01

    Glycosylation of proteins greatly affects their structure and function, but traditional genomics and transcriptomics are not able to precisely capture tissue- or species-specific glycosylation patterns. We describe here a novel approach to link different "omics" data based on exhaustive quantitative glycomics of murine dermis and epidermis. We first examined the dermal and epidermal N-glycome of mouse by a recently established glycoblotting technique. We found that the Galalpha1-3Gal epitope was solely expressed in epidermis tissue and was preferentially attached to adhesion molecules in a glycosylation site-specific manner. Clarified glycomic and protemic information combined with publicly available microarray data sets allowed us to identify galectin-3 as a receptor of Galalpha1-3Gal epitope. These findings provide mechanistic insight into the causal connection between the genotype and the phenotype seen in alpha3GalT-1-deficient mice and transgenic mice expressing endo-beta-galactosidase C. Because humans do not possess the Galalpha1-3Gal structure on their tissues, we further examined the human dermal and epidermal N-glycome. Comparative glycomics revealed that the GalNAcbeta1-4GlcNAc (N,N'-diacetyllactosediamine) epitope, instead of the Galalpha1-3Gal epitope, was highly expressed in human epidermis.

  5. Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as a Biomarker in the Mouse Model of Experimental Autoimmune Myocarditis (EAM)

    Science.gov (United States)

    Grabmaier, U.; Kania, G.; Kreiner, J.; Grabmeier, J.; Uhl, A.; Huber, B. C.; Lackermair, K.; Herbach, N.; Todica, A.; Eriksson, U.; Weckbach, L. T.; Brunner, S.

    2016-01-01

    Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of mice with coxsackie virus-induced as well as in patients with viral infection-triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a biomarker in inflammatory heart diseases remains unclear. Therefore, we investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly correlated with disease activity and progression of cardiac dysfunction in the mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide together with complete Freund`s adjuvant. ELISA revealed strong expression of cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized compared to control mice at acute and chronic stages of the disease. sVCAM-1 did not correlate with the degree of acute cardiac inflammation analyzed by histology or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM. Cardiac systolic dysfunction studied with positron emission tomography indicated a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages of the disease but showed no strong correlation with the severity of EAM. PMID:27501319

  6. Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

    Science.gov (United States)

    Ballet, Romain; Emre, Yalin; Jemelin, Stéphane; Charmoy, Mélanie; Tacchini-Cottier, Fabienne; Imhof, Beat A

    2014-12-01

    The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C) on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs) from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1) response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2) response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

  7. Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

    Directory of Open Access Journals (Sweden)

    Romain Ballet

    2014-12-01

    Full Text Available The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1 response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2 response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

  8. Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of adhesion molecule CD44

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Tomoyuki; Kitano, Ken; Terawaki, Shin-ichi; Maesaki, Ryoko; Hakoshima, Toshio, E-mail: hakosima@bs.naist.jp [Structural Biology Laboratory, Nara Institute of Science and Technology, Keihanna Science City, Nara 630-0192 (Japan)

    2007-10-01

    The radixin FERM domain complexed with the CD44 cytoplasmic tail peptide has been crystallized. A diffraction data set from the complex was collected to 2.1 Å. CD44 is an important adhesion molecule that specifically binds hyaluronic acid and regulates cell–cell and cell–matrix interactions. Increasing evidence has indicated that CD44 is assembled in a regulated manner into the membrane–cytoskeletal junction, a process that is mediated by ERM (ezrin/radixin/moesin) proteins. Crystals of a complex between the radixin FERM domain and the C-terminal cytoplasmic region of CD44 have been obtained. The crystal of the radixin FERM domain bound to the CD44 cytoplasmic tail peptide belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 62.70, b = 66.18, c = 86.22 Å, and contain one complex in the crystallographic asymmetric unit. An intensity data set was collected to a resolution of 2.1 Å.

  9. A novel COX-independent mechanism of sulindac sulfide involves cleavage of epithelial cell adhesion molecule protein.

    Science.gov (United States)

    Liggett, Jason L; Min, Kyung-Won; Smolensky, Dmitriy; Baek, Seung Joon

    2014-08-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used over the counter to treat headaches and inflammation as well as clinically to prevent cancer among high-risk groups. The inhibition of cyclooxygenase (COX) activity by NSAIDs plays a role in their anti-tumorigenic properties. NSAIDs also have COX-independent activity which is not fully understood. In this study, we report a novel COX-independent mechanism of sulindac sulfide (SS), which facilitates a previously uncharacterized cleavage of epithelial cell adhesion molecule (EpCAM) protein. EpCAM is a type I transmembrane glycoprotein that has been implemented as an over-expressed oncogene in many cancers including colon, breast, pancreas, and prostate. We found EpCAM to be down-regulated by SS in a manner that is independent of COX activity, transcription regulation, de novo protein synthesis, and proteasomal degradation pathway. Our findings clearly demonstrate that SS drives cleavage of the extracellular portion of EpCAM near the N-terminus. This SS driven cleavage is blocked by a deleting amino acids 55-81 as well as simply mutating arginine residues at positions 80 and 81 to alanine of EpCAM. Proteolysis of EpCAM by SS may provide a novel mechanism by which NSAIDs affect anti-tumorigenesis at the post-translational level.

  10. Plasma soluble vascular adhesion molecule-1 levels are persistently elevated during the first month after colorectal cancer resection.

    Science.gov (United States)

    Shantha Kumara, H M C; Tohme, Samer T; Herath, Sonali A C; Yan, Xiaohong; Senagore, Anthony J; Nasar, Abu; Kalady, Matthew F; Baxter, Raymond; Whelan, Richard L

    2012-06-01

    Plasma from the second and third weeks after minimally invasive colorectal resection (MICR) has high levels of the proangiogenic proteins VEGF and angiopoietin 2 and also stimulates, in vitro, endothelial cell (EC) proliferation and migration, which are critical to wound and tumor angiogenesis. Soluble vascular cell adhesion molecule-1 (sVCAM-1) stimulates EC chemotaxis and angiogenesis. The impact of MICR on blood levels of sVCAM-1 is unknown. This study's purpose was to determine plasma sVCAM-1 levels after MICR in colorectal cancer (CRC) patients. Blood samples from 90 patients (26% rectal, 74% colon) were obtained preoperatively, on postoperative days (POD) 1 and 3, and at other points during the next 2 months. The late samples were bundled into 7-day time blocks. sVCAM-1 levels were determined in duplicate via ELISA and reported as ng/ml. Student's t test was used for data analysis (significance, P MICR for CRC is associated with a persistent increase in plasma sVCAM-1 levels during the first month. This sustained increase may promote angiogenesis and stimulate the growth of residual tumor cells early after surgery.

  11. Fructosamine 3-kinase and glyoxalase I polymorphisms and their association with soluble RAGE and adhesion molecules in diabetes.

    Science.gov (United States)

    Škrha, J; Muravská, A; Flekač, M; Horová, E; Novák, J; Novotný, A; Prázný, M; Škrha, J; Kvasnička, J; Landová, L; Jáchymová, M; Zima, T; Kalousová, M

    2014-01-01

    Advanced glycation end-products (AGEs) are key players in pathogenesis of long-term vascular diabetes complications. Several enzymes such as fructosamine 3-kinase (FN3K) and glyoxalase I (GLO I) are crucial in preventing glycation processes. The aim of our study was to evaluate an association of FN3K (rs1056534, rs3848403) and GLO1 rs4746 polymorphisms with parameters of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in 595 diabetic and non-diabetic subjects. Genotypic and allelic frequencies of mentioned polymorphisms did not differ between subgroups. In diabetic patients significant differences were observed in sRAGE concentrations according to their rs1056534 and rs3848403 genotype. While GG and CG genotypes of rs1056534 with mutated G allele were associated with significant decrease of sRAGE (GG: 1055+/-458 and CG: 983+/-363 vs. CC: 1796+/-987 ng/l, p<0.0001), in rs3848403 polymorphism TT genotype with mutated T allele was related with significant sRAGE increase (TT: 1365+/-852 vs. CT: 1016+/-401 and CC: 1087+/-508 ng/l, p=0.05). Significant differences in adhesion molecules were observed in genotype subgroups of GLO1 rs4746 polymorphism. In conclusion, this is the first study describing significant relationship of FN3K (rs1056534) and (rs3848403) polymorphisms with concentration of sRAGE in patients with diabetes.

  12. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

    Directory of Open Access Journals (Sweden)

    Schachner Melitta

    2011-05-01

    Full Text Available Abstract Background L1 cell adhesion molecule (CD171 is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Methods Using a sensitive enzyme-linked immunosorbent assay (ELISA, soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Results Median levels of soluble L1 were significantly higher (p p Conclusion These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.

  13. Sulforaphane inhibits TNF-α-induced adhesion molecule expression through the Rho A/ROCK/NF-κB signaling pathway.

    Science.gov (United States)

    Hung, Chi-Nan; Huang, Hui-Pei; Wang, Chau-Jong; Liu, Kai-Li; Lii, Chong-Kuei

    2014-10-01

    Endothelial dysfunction is an early indicator of cardiovascular diseases. Increased stimulation of tumor necrosis factor-α (TNF-α) triggers the inflammatory mediator secretion of endothelial cells, leading to atherosclerotic risk. In this study, we investigated whether sulforaphane (SFN) affected the expression of intracellular adhesion molecule-1 (ICAM-1) in TNF-α-induced ECV 304 endothelial cells. Our data showed that SFN attenuated TNF-α-induced expression of ICAM-1 in ECV 304 cells. Pretreatment of ECV 304 cells with SFN inhibited dose-dependently the secretion of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and IL-8. SFN inhibited TNF-α-induced nuclear factor-κB (NF-κB) DNA binding activity. Furthermore, SFN decreased TNF-α-mediated phosphorylation of IκB kinase (IKK) and IκBα, Rho A, ROCK, ERK1/2, and plasminogen activator inhibitor-1 (PAI-1) levels. Collectively, SFN inhibited the NF-κB DNA binding activity and downregulated the TNF-α-mediated induction of ICAM-1 in endothelial cells by inhibiting the Rho A/ROCK/NF-κB signaling pathway, suggesting the beneficial effects of SFN on suppression of inflammation within the atherosclerotic lesion.

  14. IgLON cell adhesion molecules are shed from the cell surface of cortical neurons to promote neuronal growth.

    Science.gov (United States)

    Sanz, Ricardo; Ferraro, Gino B; Fournier, Alyson E

    2015-02-13

    Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons.

  15. Relationships between neuronal cell adhesion molecule and LHRH neurons in the urodele brain: a developmental immunohistochemical study

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    S Gianola

    2009-12-01

    Full Text Available Polysialic acid (PSA, a homopolymer attached to neural cell adhesion molecule (NCAM is considered a major hallmark of vertebrate cell migration. We studied the distribution of PSA-NCAM by immunohistochemistry, during brain development, in two urodele amphibians, Pleurodeles waltl and the neotenic newt Ambystoma mexicanum. In both species a gradual increase of immunolabelling was observed throughout the brain from developmental stage 30 to stage 52. At the onset of metamorphosis, some differences became evident: in Pleurodeles immunostaining was gradually restricted to the olfactory system while in Ambystoma, PSA-NCAM maintained a more extended distribution (for example throughout the telencephalic walls suggesting, for the brain of this latter species, a rather preserved neuronal plasticity. The aim of the present work was to correlate the above described PSA-NCAMimmunoreactivity (IR with the distribution of luteinizing hormone-releasing hormone (LH-RH containing neurons, which represent a well known example of neural elements migrating from the olfactory placode. LHRH-IR, undetectable till stage 30, was later found together with PSA-NCAM-IR in both the olfactory system and septo-hypothalamic areas. Such observations further support a role of PSA in providing a migration route toward the establishment of a part, at least, of the urodele LHRH system. The possible functional meaning of the LHRH-containing neurons localized between dorsal and ventral thalamus of Ambystoma, never reported before in this area, almost devoid of PSANCAM- IR, is discussed.

  16. Time-dependent changes in the expression of lymphocyte and monocyte cell adhesion molecules after meals of different composition.

    Science.gov (United States)

    Torrecilla, Esther; González-Muñoz, Miguel; Lahoz, Carlos; Mostaza, Jose

    2010-12-01

    The objective of the present study was to compare the acute effect of meals of different composition on the expression of adhesion molecules that play a key role in leucocyte trafficking. A total of twenty apparently healthy subjects randomly consumed three isoenergetic meals 1 week apart: enriched in carbohydrates (CHO), enriched in monounsaturated fat and enriched in saturated fat. Blood samples were obtained before the meals and at 2, 4, 6, 8 and 10 h after meal ingestion. Samples were analysed for LDL resistance to Cu-mediated oxidation and for the surface expression on peripheral blood mononuclear cells (PBMC) of CD62L, CD162, CD11a, CD11b, CD49d and CD54 by flow cytometry. The present results showed that there were no changes in LDL susceptibility to oxidation within and among the meals. After the CHO-enriched meal, there was a time-dependent increased expression of CD162, CD49d, CD11a and CD54 on PBMC that returned to basal values after 8-10 h. These changes were significantly greater than the ones observed after the consumption of the monounsaturated fat- and the saturated fat-enriched meals and were more evident in lymphocytes than in monocytes. In conclusion, acute ingestion of a CHO-enriched meal induces higher increases of lymphocyte activation markers than fat-enriched meals. These results suggest that long-term consumption of CHO-enriched diets may be associated with a sustained pro-inflammatory state.

  17. IgLON Cell Adhesion Molecules Are Shed from the Cell Surface of Cortical Neurons to Promote Neuronal Growth*

    Science.gov (United States)

    Sanz, Ricardo; Ferraro, Gino B.; Fournier, Alyson E.

    2015-01-01

    Matrix metalloproteinases and a disintegrin and metalloproteinases are members of the zinc endopeptidases, which cleave components of the extracellular matrix as well as cell surface proteins resulting in degradation or release of biologically active fragments. Surface ectodomain shedding affects numerous biological processes, including survival, axon outgrowth, axon guidance, and synaptogenesis. In this study, we evaluated the role of metalloproteinases in regulating cortical neurite growth. We found that treatment of mature cortical neurons with pan-metalloproteinase inhibitors or with tissue inhibitors of metalloproteinase-3 reduced neurite outgrowth. Through mass spectrometry, we characterized the metalloproteinase-sensitive cell surface proteome of mature cortical neurons. Members of the IgLON family of glycosylphosphatidylinositol-anchored neural cell adhesion molecules were identified and validated as proteins that were shed from the surface of mature cortical neurons in a metalloproteinase-dependent manner. Introduction of two members of the IgLON family, neurotrimin and NEGR1, in early embryonic neurons was sufficient to confer sensitivity to metalloproteinase inhibitors in neurite outgrowth assays. Outgrowth experiments on immobilized IgLON proteins revealed a role for all IgLON family members in promoting neurite extension from cortical neurons. Together, our findings support a role for metalloproteinase-dependent shedding of IgLON family members in regulating neurite outgrowth from mature cortical neurons. PMID:25538237

  18. Carcinoembryonic antigen-related cell adhesion molecules (CEACAM 1, 5 and 6 as biomarkers in pancreatic cancer.

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    Florian Gebauer

    Full Text Available BACKGROUND: Aim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM 1, 5 and 6 in pancreatic adenocarcinoma (PDAC. EXPERIMENTAL DESIGN: CEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC and by enzyme linked immunosorbent assays. RESULTS: Presence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS. The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group. CONCLUSION: The effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis.

  19. Structure and Mutagenesis of Neural Cell Adhesion Molecule Domains Evidence for Flexibility in the Placement of Polysialic Acid Attachment Sites

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Deirdre A.; Swartzentruber, Kristin G.; Lavie, Arnon; Colley, Karen J. (UICM)

    2010-11-09

    The addition of {alpha}2,8-polysialic acid to the N-glycans of the neural cell adhesion molecule, NCAM, is critical for brain development and plays roles in synaptic plasticity, learning and memory, neuronal regeneration, and the growth and invasiveness of cancer cells. Our previous work indicates that the polysialylation of two N-glycans located on the fifth immunoglobulin domain (Ig5) of NCAM requires the presence of specific sequences in the adjacent fibronectin type III repeat (FN1). To understand the relationship of these two domains, we have solved the crystal structure of the NCAM Ig5-FN1 tandem. Unexpectedly, the structure reveals that the sites of Ig5 polysialylation are on the opposite face from the FN1 residues previously found to be critical for N-glycan polysialylation, suggesting that the Ig5-FN1 domain relationship may be flexible and/or that there is flexibility in the placement of Ig5 glycosylation sites for polysialylation. To test the latter possibility, new Ig5 glycosylation sites were engineered and their polysialylation tested. We observed some flexibility in glycosylation site location for polysialylation and demonstrate that the lack of polysialylation of a glycan attached to Asn-423 may be in part related to a lack of terminal processing. The data also suggest that, although the polysialyltransferases do not require the Ig5 domain for NCAM recognition, their ability to engage with this domain is necessary for polysialylation to occur on Ig5 N-glycans.

  20. Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells

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    Stanislav V. Sosnovtsev

    2017-02-01

    Full Text Available The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1, was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.

  1. L1 cell adhesion molecule as a predictor for recurrence in pulmonary carcinoids and large-cell neuroendocrine tumors.

    Science.gov (United States)

    Kim, Hyo Song; Yi, Seong Yoon; Jun, Hyun Jung; Ahn, Jin Seok; Ahn, Myung-Ju; Lee, Jeeyun; Kim, Youngwook; Cui, Zheng Yun; Hong, Hyo Jeong; Kim, Jin-Man; Li, Shengjin; Hwang, In Gyu; Park, Keunchil

    2009-02-01

    Pulmonary neuroendocrine tumors are a distinct subset of neoplasms with indolent to aggressive behavior. This study was conducted to evaluate the prognostic role of L1 cell adhesion molecule (L1CAM) in pulmonary neuroendocrine tumors. We retrospectively analyzed L1 expression in 55 cases of completely resected carcinoids and large-cell neuroendocrine carcinomas, by the immunohistochemistry with monoclonal antibody A10-A3 against human L1. L1 immunoreactivity was detected in 34 (61.8%) of 55 specimens. There was a significant correlation between L1 expression and the World Health Organization classification of this tumor (Spearman rank correlation, rho=0.60, p<0.001). With median follow-up of 52.0 months, the 5-year survival rate for patients with low expression of L1 (<20% of tumor cells stained) was significantly better compared with those with high expression of L1 (82.6% vs. 43.7%, p=0.005). L1 was also a significant independent predictor of disease-free survival, and patients with high L1 expression have a higher risk for recurrence compared with those with low L1 expression (hazard ratio, 3.0; 95% confidence interval, 1.2-8.3; p=0.034). L1 expression is significantly associated with aggressiveness and further studies with larger samples are needed to validate potential prognostic value for pulmonary neuroendocrine tumors.

  2. Gram-Negative Pneumonia Alters Large-Vein Cell-Adhesion Molecule Profile and Potentiates Experimental Stasis Venous Thrombosis.

    Science.gov (United States)

    Obi, Andrea T; Andraska, Elizabeth; Kanthi, Yogendra; Luke, Catherine E; Elfline, Megan; Madathilparambil, Suresh; Siahaan, Teruna J; Jaffer, Farouc A; Wakefield, Thomas W; Raghavendran, Krishnan; Henke, Peter K

    2016-01-01

    Pneumonia is a significant risk factor for the development of venous thrombosis (VT). Cell-adhesion molecules (CAMs) are linked to the pathogenesis of both pneumonia and VT. We hypothesized that remote infection would confer a prothrombogenic milieu via systemic elevation of CAMs. Lung injury was induced in wild-type (C57BL/6) mice by lung contusion or intratracheal inoculation with Klebsiella pneumoniae or saline controls. K. pneumoniae-treated mice and controls additionally underwent inferior vena cava (IVC) ligation to generate VT. Lung-contusion mice demonstrated no increase in E-selectin or P-selectin whereas mice infected with K. pneumoniae demonstrated increased circulating P-selectin, ICAM-1, VCAM-1 and thrombin-antithrombin (TAT) complexes. Mice with pneumonia formed VT 3 times larger than controls, demonstrated significantly more upregulation of vein-wall and systemic CAMs, and formed erythrocyte-rich thrombi. Elevated CAM expression was identified in mice with pneumonia, but not lung contusion, indicating that the type of inflammatory stimulus and the presence of infection drive the vein-wall response. Elevation of CAMs was associated with amplified VT and may represent an alternate mechanism by which to target the prevention of VT. © 2016 S. Karger AG, Basel.

  3. 活化白细胞黏附分子与肿瘤%Activated leukocyte cell adhesion molecule and minors

    Institute of Scientific and Technical Information of China (English)

    柯少迎; 庄建良; 潘群雄

    2009-01-01

    Activated leukocyte cell adhesion molecule (ALCAM) is a member of immunoglobulin gene superfamily. It is manily expressed in leucocytes and thymic epithelial cells. ALCAM mediates both heterophilic (ALCAM-CD6) and homophilic(ALCAM-ALCAM) cell-cell interactions. Studies show that ALCAM is highly expressed on multiple tumor cells and plays a role in tumorigenesis and tumor progression. ALCAM expression is closely correlated with several human tumors, including breast cancer, esophageal carcinoma, colon carcinoma, o-varian caneer,hepatocellular carcinoma and malignant melanoma.%活化自细胞黏附分子(ALCAM)是免疫球蛋白基因超家族成员,主要表达在白细胞和胸腺上皮细胞.ALCAM在细胞间异嗜性黏附和同嗜性黏附中起重要作用.研究表明,ALCAM在多种肿瘤细胞表面高表达,参与肿瘤的发生发展,在人类肿瘤,ALCAM的表达与乳腺癌、食管癌、结肠癌、卵巢癌、肝癌及恶性黑色素瘤等密切相关.

  4. Influence of short-term changes in sex hormones on serum concentrations of cellular adhesion molecules in young healthy women

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    Ivana Begić

    2012-02-01

    Full Text Available Aim To determine if short-term changes in sex hormones (such as cyclic changes within the menstrual cycle can influence the serumconcentration of soluble cell adhesion molecules (CAMs.Methods Sixteen healthy young women with normal cycles participated in this study. Serum levels of sICAM-1, sVCAM-1 and E-selectin were determined in three different phases of the menstrual cycle: a early follicular (EF phase, b ovulatory (O phase and c midluteal (ML phase, by standardized ELISA-based kits. To confirm the exact assessment of menstrual cycle phases, serum levels of estrogen, progesterone, LH and FSH were measured. Results There were significant oscillations in serum female sex hormones concentration over the cycle duration, as expected the level of estrogen (E2 and progesterone (PROG was the lowest in EF phase, the highest E2 appeared in O phase, and both E2 and PROG were present in high concentrations during ML phase. There was a significant positive correlation between E2 and serum soluble ICAM -1 concentrations (p=0,041, correlation coefficient 0,306. However, there was no significant change in other soluble CAMs concentration during the menstrual cycle. Conclusion Results of our study suggest that short-term changes in female sex hormone levels could modulate expression of soluble ICAM-1, but not VCAM -1 or E-selectin in extent that would affect a young woman’s health.

  5. Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures.

    Science.gov (United States)

    White, Kimberly M R; Sabatino, Julia A; He, Min; Davis, Natalie; Tang, Ningfeng; Bearer, Cynthia F

    2016-07-01

    Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1 through lipid rafts. Our objective is to determine if toluene inhibits L1-mediated NOG and toluene inhibits L1 signaling at concentrations achieved during occupational exposure. Concentrations of toluene reflective of blood concentrations achieved in solvent abusers and occupational settings are used. Cerebellar granule neurons (CGN) harvested from postnatal day 6 rat pups are plated on coverslips coated with poly-L-lysine (PLL) alone or PLL followed by laminin. L1 is added to the media of CGN plated on PLL alone. Toluene is added 2 h after plating. Cells are fixed at 24 h and neurite length is measured. ERK1/2 activation by L1 in CGN is analyzed by immunoblot. Toluene significantly reduced mean neurite length of CGN exposed to L1 but not laminin. Toluene significantly reduced L1-mediated ERK1/2 phosphorylation. Results suggest that toluene inhibits L1-lipid raft interactions at occupationally relevant concentrations and may lead to a fetal solvent spectrum disorder similar to fetal alcohol spectrum disorder.

  6. Regulation by gut commensal bacteria of carcinoembryonic antigen-related cell adhesion molecule expression in the intestinal epithelium.

    Science.gov (United States)

    Kitamura, Yasuaki; Murata, Yoji; Park, Jung-Ha; Kotani, Takenori; Imada, Shinya; Saito, Yasuyuki; Okazawa, Hideki; Azuma, Takeshi; Matozaki, Takashi

    2015-07-01

    Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 1 and CEACAM20, immunoglobulin superfamily members, are predominantly expressed in intestinal epithelial cells (IECs) and co-localized at the apical surface of these cells. We here showed that the expression of mouse CEACAM1 and CEACAM20 at both mRNA and protein levels was markedly reduced in IECs of the small intestine by the treatment of mice with antibiotics against Gram-positive bacteria. The expression of both proteins was also decreased in IECs of the small intestine from germ-free mice, compared with that from control specific-pathogen-free mice. Exposure of intestinal organoids to IFN-γ markedly increased the expression of either CEACAM1 or CEACAM20, whereas the exposure to TNF-α increased the expression of the former protein, but not that of the latter. In contrast, the expression of CEACAM20, but not of CEACAM1, in intestinal organoids was markedly increased by exposure to butyrate, a short-chain fatty acid produced by bacterial fermentation in the intestine. Collectively, our results suggest that Gram-positive bacteria promote the mRNA expression of CEACAM1 or CEACAM20 in the small intestine. Inflammatory cytokines or butyrate likely participates in such effects of commensal bacteria.

  7. Stability, structural and electronic properties of benzene molecule adsorbed on free standing Au layer

    Energy Technology Data Exchange (ETDEWEB)

    Katoch, Neha, E-mail: nehakatoch2@gmail.com; Kapoor, Pooja; Sharma, Munish; Ahluwalia, P. K. [Physics Department, Himachal Pradesh University, Shimla, Himachal Pradesh, India 171005 (India); Kumar, Ashok [Center for Physical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, India, 151001 (India)

    2016-05-23

    We report stability and electronic properties of benzene molecule adsorbed on the Au atomic layer within the framework of density function theory (DFT). Horizontal configuration of benzene on the top site of Au monolayer prefers energetically over other studied configurations. On the adsorption of benzene, the ballistic conductance of Au monolayer is found to decrease from 4G{sub 0} to 2G{sub 0} suggesting its applications for the fabrications of organic sensor devices based on the Au atomic layers.

  8. Targeting cell adhesion molecules with nanoparticles using in vivo and flow-based in vitro models of atherosclerosis.

    Science.gov (United States)

    Khodabandehlou, Khosrow; Masehi-Lano, Jacqueline J; Poon, Christopher; Wang, Jonathan; Chung, Eun Ji

    2017-04-01

    Atherosclerosis is a leading cause of death worldwide; in addition to lipid dysfunction, chronic arterial wall inflammation is a key component of atherosclerosis. Techniques that target cell adhesion molecules, which are overexpressed during inflammation, are effective methods to detect and treat atherosclerosis. Specifically, research groups have identified vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule, and selectins (E-selectin and P-selectin) as correlated to atherogenesis. In this review, we discuss recent strategies both in vivo and in vitro that target cell adhesion molecules. First, we discuss peptide-based and antibody (Ab)-based nanoparticles utilized in vivo for diagnostic, therapeutic, and theranostic applications. Second, we discuss flow-based in vitro models that serve to reduce the traditional disadvantages of in vivo studies such as variability, time to develop the disease, and ethical burden, but preserve physiological relevance. The knowledge gained from these targeting studies can be translated into clinical solutions for improved detection, prevention, and treatment of atherosclerosis. Impact statement As atherosclerosis remains the leading cause of death, there is an urgent need to develop better tools for treatment of the disease. The ability to improve current treatments relies on enhancing the accuracy of in vitro and in vivo atherosclerotic models. While in vivo models provide all the relevant testing parameters, variability between animals and among models used is a barrier to reproducible results and comparability of NP efficacy. In vitro cultures isolate cells into microenvironments that fail to take into account flow separation and shear stress, which are characteristics of atherosclerotic lesions. Flow-based in vitro models provide more physiologically relevant platforms, bridging the gap between in vivo and 2D in vitro models. This is the first review that

  9. An active film-coating approach to enhance chemical stability of a potent drug molecule.

    Science.gov (United States)

    Desai, Divyakant; Rao, Venkatramana; Guo, Hang; Li, Danping; Stein, Daniel; Hu, Frank Y; Kiesnowski, Chris

    2012-01-01

    Peliglitazar, a PPAR α/γ agonist, was found to undergo acid as well as base catalyzed degradation. The acid catalyzed degradation led to the formation of benzylic alcohol and glycine carbamate and the base catalyzed degradation led to formation of p-hydroxyanisole and an amine degradant. In capsule formulations, the capsules with the lowest drug-loading exhibited maximum instability even at 25 °C/60% RH storage condition. Incorporation of pH-modifiers to maintain 'micro-environmental pH' acidic did not prevent the formation of the base-catalyzed degradants. Traditional dry granulated tablet formulation which is qualitatively similar to the capsule formulations showed the presence of acid-catalyzed degradants even without the presence of an acidifying agent. On the other hand, traditional wet granulated tablet formulation showed mainly base-catalyzed degradants. Stability problems of the tablet formulation were aggravated because the potent molecule required low tablet strengths which resulted in low drug to excipient ratio. To stabilize the molecule, an active film-coating approach was explored. In this approach, the drug was sprayed with the coating material onto non-active containing tablet cores. This approach of trapping the drug particles into the coating material provided tablets with satisfactory chemical stability. The stability enhancement observed in the active coating approach is attributed to the higher drug to excipient ratio in the film coat of non-reactive coating material compared to that in the traditional dry or wet granulated formulations.

  10. Upregulation of endothelial cell adhesion molecules characterizes veins close to granulomatous infiltrates in the renal cortex of cats with feline infectious peritonitis and is indirectly triggered by feline infectious peritonitis virus-infected monocytes in vitro.

    Science.gov (United States)

    Acar, Delphine D; Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Roukaerts, Inge D M; Baetens, Wendy; Van Bockstael, Sebastiaan; De Gryse, Gaëtan M A; Desmarets, Lowiese M B; Nauwynck, Hans J

    2016-10-01

    One of the most characteristic pathological changes in cats that have succumbed to feline infectious peritonitis (FIP) is a multifocal granulomatous phlebitis. Although it is now well established that leukocyte extravasation elicits the inflammation typically associated with FIP lesions, relatively few studies have aimed at elucidating this key pathogenic event. The upregulation of adhesion molecules on the endothelium is a prerequisite for stable leukocyte-endothelial cell (EC) adhesion that necessarily precedes leukocyte diapedesis. Therefore, the present work focused on the expression of the EC adhesion molecules and possible triggers of EC activation during the development of FIP. Immunofluorescence analysis revealed that the endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was elevated in veins close to granulomatous infiltrates in the renal cortex of FIP patients compared to non-infiltrated regions and specimens from healthy cats. Next, we showed that feline venous ECs become activated when exposed to supernatant from feline infectious peritonitis virus (FIPV)-infected monocytes, as indicated by increased adhesion molecule expression. Active viral replication seemed to be required to induce the EC-stimulating activity in monocytes. Finally, adhesion assays revealed an increased adhesion of naive monocytes to ECs treated with supernatant from FIPV-infected monocytes. Taken together, our results strongly indicate that FIPV activates ECs to increase monocyte adhesion by an indirect route, in which proinflammatory factors released from virus-infected monocytes act as key intermediates.

  11. Human Sarcoma growth is sensitive to small-molecule mediated AXIN stabilization.

    Directory of Open Access Journals (Sweden)

    Alessandra De Robertis

    Full Text Available Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas.

  12. Small-molecule stabilization of protein-protein interactions: an underestimated concept in drug discovery?

    Science.gov (United States)

    Thiel, Philipp; Kaiser, Markus; Ottmann, Christian

    2012-02-27

    The modulation of protein-protein interactions (PPIs) has been recognized as one of the most challenging tasks in drug discovery. While their systematic development has long been considered as intractable, this view has changed over the last years, with the first drug candidates undergoing clinical studies. To date, the vast majority of PPI modulators are interaction inhibitors. However, in many biological contexts a prolonged lifespan of a PPI might be desirable, calling for the complementary approach of PPI stabilization. In fact, nature offers impressive examples of this concept and some PPI-stabilizing natural products have already found application as important drugs. Moreover, directed small-molecule stabilization has recently been demonstrated. Therefore, it is time to take a closer look at the constructive side of modulating PPIs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Surface modification of polyethylene by radiation-induced grafting for adhesive bonding. III. Oxidative degradation and stabilization of grafted layer

    Energy Technology Data Exchange (ETDEWEB)

    Yamakawa, S.; Yamamoto, F.

    1978-09-01

    Vapor-phase mutual grafting of methyl acrylate (MA) onto polyethylene (PE) and subsequent saponification treatment produce a surface graft having a high adhesive bondability, which results from the presence of a hydrolized homopolymer layer (consisting of only monomer componenet) on an inner graft copolymer layer consisting of both PE and monomer components. The oxidative deterioration and the stabilization of the grated surface layer have been investigated to clarify the long-term stability of the adhesive bondability. The bondability rapidly disappears with accelerated weatherly followed by acetone extraction treatment, whereas it is kept unchanged during thermal-oxidative aging at 100/sup 0/C. Microscopic and attenuated total resonance (ATR) infrared spectroscopic observations of the degreaded surfaces show that the bondability loss is due to degradiative removal of the surface homopolymer layer. The addition of combinations of conventional antioxidants and ultraviolet absorbers stabilizes the grafted surface layer against thermal-oxidative and photo-oxidative degradation and thus extends the bondability rentention time. The stabilization is more effective in the grafts of carbon black-containing PE, where carbon black is present in the inner-graft copolymer layer.

  14. Orthogonal Control of Stability and Tunable Dry Adhesion by Tailoring the Shape of Tapered Nanopillar Arrays.

    Science.gov (United States)

    Cho, Younghyun; Kim, Gyuseok; Cho, Yigil; Lee, Su Yeon; Minsky, Helen; Turner, Kevin T; Gianola, Daniel S; Yang, Shu

    2015-12-16

    Tapered nanopillar structures of different cross-sectional geometries including cone-, pencil-like, and stepwise are prepared from anodized aluminum oxide templates. The shape effect on the adhesion strength is investigated in experiments and simulation. Cone-shaped nanopillars are highly bendable under load and can recover after unloading, thus, warranting high adhesion strength, 34 N cm(-2) . The pencil-like and stepwise nano-pillars are, however, easily fractured and are not recoverable under the same conditions.

  15. Theoretical Insights into Three Types of Oxidized Starch-Based Adhesives: Chemical Stability, Water Resistance, and Shearing Viscosity from a Molecular Viewpoint

    Directory of Open Access Journals (Sweden)

    Liang Junxi

    2016-01-01

    Full Text Available To better understand the origin and difference associated with chemical stability, water resistance, and shearing viscosity of three types of different oxidized modified starch-based adhesives, a detailed theoretical investigation from a molecular viewpoint has been performed using the AM1 semiempirical level and the DFT-B3LYP level, respectively. As a result, our findings suggest that, by Mulliken population analysis (MPA, frontier orbital analysis, and electrostatic potential (EP analysis based on B3LYP/6-31G calculations, the chemical stability, water resistance, and shearing viscosity of the oxidized modified starch-based adhesives are uniformly improved and corresponding difference for each property presents an identical order: the oxidized grafted cross-linked starch-based adhesive > the oxidized grafted starch-based adhesive > the oxidized starch-based adhesive, which is well consistent with experimental results.

  16. Sesamin attenuates intercellular cell adhesion molecule-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in apolipoprotein-E-deficient mice.

    Science.gov (United States)

    Wu, Wen-Huey; Wang, Shu-Huei; Kuan, I-I; Kao, Ya-Shi; Wu, Pei-Jhen; Liang, Chan-Jung; Chien, Hsiung-Fei; Kao, Chiu-Hua; Huang, Ching-Jang; Chen, Yuh-Lien

    2010-09-01

    Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.

  17. Changes in adhesion molecule expression and oxidative burst activity of granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass compared with abdominal surgery

    DEFF Research Database (Denmark)

    Toft, P; Nielsen, C H; Tønnesen, E

    1998-01-01

    Cardiac and major abdominal surgery are associated with granulocytosis in peripheral blood. The purpose of the present study was to describe the granulocyte and monocyte oxidative burst and the expression of adhesion molecules following cardiac surgery with cardiopulmonary bypass and abdominal...... surgery. The ability to respond with an oxidative burst was measured by means of flow cytometry using 123-dihydrorhodamine. The adhesion molecules CD11a/CD18, CD11c/CD18, CD44 were measured using monoclonal antibodies. Blood samples from eight patients undergoing open-heart surgery were taken before...... surgery, 1, 5, 10 and 20 min after aortic clamping, and then 1, 5, 10 and 20 min and 1, 2 and 3 h after declamping. Samples from eight patients undergoing abdominal surgery were taken before surgery, at the end of surgery, and 2 and 3 h post-operatively. A decrease in number of granulocytes and monocytes...

  18. Short communication: Conservation of Streptococcus uberis adhesion molecule and the sua gene in strains of Streptococcus uberis isolated from geographically diverse areas.

    Science.gov (United States)

    Yuan, Ying; Dego, Oudessa Kerro; Chen, Xueyan; Abadin, Eurife; Chan, Shangfeng; Jory, Lauren; Kovacevic, Steven; Almeida, Raul A; Oliver, Stephen P

    2014-12-01

    The objective was to identify and sequence the sua gene (GenBank no. DQ232760; http://www.ncbi.nlm.nih.gov/genbank/) and detect Streptococcus uberis adhesion molecule (SUAM) expression by Western blot using serum from naturally S. uberis-infected cows in strains of S. uberis isolated in milk from cows with mastitis from geographically diverse areas of the world. All strains evaluated yielded a 4.4-kb sua-containing PCR fragment that was subsequently sequenced. Deduced SUAM AA sequences from those S. uberis strains evaluated shared >97% identity. The pepSUAM sequence located at the N terminus of SUAM was >99% identical among strains of S. uberis. Streptococcus uberis adhesion molecule expression was detected in all strains of S. uberis tested. These results suggest that sua is ubiquitous among strains of S. uberis isolated from diverse geographic locations and that SUAM is immunogenic.

  19. Endometrial Expression of Homeobox Genes and Cell Adhesion Molecules in Infertile Women With Intramural Fibroids During Window of Implantation.

    Science.gov (United States)

    Makker, Annu; Goel, Madhu Mati; Nigam, Dipti; Bhatia, Vikram; Mahdi, Abbas Ali; Das, Vinita; Pandey, Amita

    2017-03-01

    This study was designed to examine the expression and cellular distribution of homeobox ( HOX) genes ( HOXA10 and HOXA11) and cell adhesion molecules (E-cadherin, N-cadherin, and β-catenin) during the window of implantation in infertile women with noncavity-distorting intramural (IM) fibroids (n = 18) and in fertile controls (n = 12). Quantitative real-time polymerase chain reaction and immunohistochemistry were used to evaluate the messenger RNA (mRNA) levels and protein expression, respectively. When compared to fertile controls, reduced HOXA10 and HOXA11 transcript and protein levels were observed in infertile women. However, changes only in the expression of HOXA10 mRNA (-1.72-fold; P = .03) and stromal protein ( P = .001) were statistically significant. Significantly lower E-cadherin mRNA (-10.97-fold; P = .02) and protein levels were seen in infertile patients. E-cadherin immunostaining was significantly reduced both in the luminal ( P = .048) and in the glandular ( P = .014) epithelium of endometrium from infertile patients when compared to controls. No significant change was observed either in the mRNA levels or in the immunoexpression of N-cadherin and β-catenin. However, a trend toward lower N-cadherin expression in the luminal epithelium ( P = .054) and decreased β-catenin expression in the glandular epithelium ( P = .070) was observed in infertile patients. The present findings suggest that altered endometrial HOXA10 and E-cadherin mRNA and protein expression observed in infertile women with IM fibroids during the mid-secretory phase might impair endometrial receptivity leading to infertility in these patients.

  20. Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice.

    Directory of Open Access Journals (Sweden)

    Selina Christen

    Full Text Available Type 1 diabetes (T1D results from the autoimmune destruction of insulin-producing beta-cells in the pancreas. Recruitment of inflammatory cells is prerequisite to beta-cell-injury. The junctional adhesion molecule (JAM family proteins JAM-B and JAM-C are involved in polarized leukocyte transendothelial migration and are expressed by vascular endothelial cells of peripheral tissue and high endothelial venules in lympoid organs. Blocking of JAM-C efficiently attenuated cerulean-induced pancreatitis, rheumatoid arthritis or inflammation induced by ischemia and reperfusion in mice. In order to investigate the influence of JAM-C on trafficking and transmigration of antigen-specific, autoaggressive T-cells, we used transgenic mice that express a protein of the lymphocytic choriomeningitis virus (LCMV as a target autoantigen in the β-cells of the islets of Langerhans under the rat insulin promoter (RIP. Such RIP-LCMV mice turn diabetic after infection with LCMV. We found that upon LCMV-infection JAM-C protein was upregulated around the islets in RIP-LCMV mice. JAM-C expression correlated with islet infiltration and functional beta-cell impairment. Blockade with a neutralizing anti-JAM-C antibody reduced the T1D incidence. However, JAM-C overexpression on endothelial cells did not accelerate diabetes in the RIP-LCMV model. In summary, our data suggest that JAM-C might be involved in the final steps of trafficking and transmigration of antigen-specific autoaggressive T-cells to the islets of Langerhans.

  1. L1 cell adhesion molecule induces melanoma cell motility by activation of mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yi, Young-Su; Baek, Kwang-Soo; Cho, Jae Youl

    2014-06-01

    L1 cell adhesion molecule (L1CAM) is highly expressed in various types of cancer cells and has been implicated in the control of cell proliferation and motility. Recently, L1CAM was reported to induce the motility of melanoma cells, but the mechanism of this induction remains poorly understood. In this study, we investigated the molecular mechanisms by which L1CAM induces the motility of melanoma cells. Unlike other types of cancer cells, B16F10 melanoma cells highly expressed L1CAM at both the RNA and protein levels, and the expression of L1CAM induced AP-1 activity. In accordance to AP-1 activation, MAPK signaling pathways were activated by L1CAM. Inhibition of L1CAM expression by L1CAM-specific siRNA suppressed the activation of MAPKs such as ERK and p38. However, no significant change was observed in JNK activation. As expected, upstream MAP2K, MKK3/6, MAP3K, and TAK1 were also deactivated by the inhibition of L1CAM expression. L1CAM induced the motility of B16F10 cells. Inhibition of L1CAM expression suppressed migration and invasion of B16F10 cells, but no suppressive effect was observed on their proliferation and anti-apoptotic resistance. Treatment of B16F10 cells with U0126, an ERK inhibitor, or SB203580, a p38 inhibitor, suppressed the migration and invasion abilities of B16F10 cells. Taken together, our results suggest that L1CAM induces the motility of B16F10 melanoma cells via the activation of MAPK pathways. This finding provides a more detailed molecular mechanism of L1CAM-mediated induction of melanoma cell motility.

  2. Differential Expression of Extracellular Matrix and Adhesion Molecules in Fetal-Origin Amniotic Epithelial Cells of Preeclamptic Pregnancy.

    Directory of Open Access Journals (Sweden)

    Myung-Sun Kim

    Full Text Available Preeclampsia is a common disease that can occur during human pregnancy and is a leading cause of both maternal and neonatal morbidity and mortality. Inadequate trophoblast invasion and deficient remodeling of uterine spiral arteries are associated with preeclampsia (PE. The development of this syndrome is thought to be related to multiple factors. Recently, we isolated patient-specific human amniotic epithelial cells (AECs from the placentas of 3 women with normal pregnancy and 3 with preeclamptic pregnancy. Since the characteristics of human AECs in PE are different from those in normal pregnancy, we sought to confirm the genes differentially expressed between preeclamptic pregnancy and normal pregnancy. Therefore, we performed transcriptome analysis to investigate the candidate genes associated with the possible pathophysiology of preeclampsia. Pathway analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID and Kyoto Encyclopedia of Genes and Genomes (KEGG online resource. In this study, we selected a total of 12 pathways and focused on extracellular matrix-related and biological adhesion molecules. Using RT-PCR array and real-time PCR, we confirmed that COL16A1, ITGB2, and LAMA3 were significantly up-regulated, but ITGA1, ITGA3, ITGA6, MMP1, MMP3, MMP10 and MMP11 were significantly down-regulated in preeclamptic fetal origin cells. Taken together, we suggest that the genes and pathways identified here may be responsible for the occurrence and development of PE, and controlling their expression may play a role in communication with fetal-maternal placenta to keep normal pregnancy.

  3. Could both vitamin D and geomagnetic activity impact serum levels of soluble cell adhesion molecules in young men?

    Science.gov (United States)

    Bleizgys, Andrius; Šapoka, Virginijus

    2016-07-01

    Vitamin D might have a role in diminishing endothelial dysfunction (ED). The initial aim was to test the hypothesis of reciprocity between levels of 25-hydroxyvitamin D (25(OH)D) and levels of soluble endothelial cell adhesion molecules (CAMs) that could serve as biomarkers of ED. Randomly selected men of age 20-39 were examined at February or March (cold season) and reexamined at August or September (warm season). Some lifestyle and anthropometrical data were recorded. Laboratory measurements, including those for serum levels of soluble CAMs—sICAM-1, sVCAM-1, sE-selectin and sP-selectin—were also performed. As some of the results were rather unexpected, indices of geomagnetic activity (GMA), obtained from the online database, were included in further analysis as a confounder. In 2012-2013, 130 men were examined in cold season, and 125 of them were reexamined in warm season. 25(OH)D levels were found to be significantly negatively associated with sVCAM-1 levels ( β = -0.15, p = 0.043 in warm season; β = -0.19, p = 0.007 for changes). Levels of sVCAM-1 and sICAM-1 from the same seasons were notably different between years and have changed in an opposite manner. Soluble P-selectin levels were higher at warm season in both years. GMA was positively associated with sVCAM-1 ( β = 0.17, p = 0.039 in cold season; β = 0.22, p = 0.002 for changes) and negatively with sICAM-1 ( β = -0.30. p Vitamin D might play a role in diminishing sVCAM-1 levels. Levels of sVCAM-1 and sICAM-1 were associated with the GMA; this implies a need for further research.

  4. Effects of anisodamine on the expressions of vascular endothelial growth factor and intercellular adhesion molecule 1 in experimental infusion phlebitis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhen-xiang; WANG Peng; ZHANG Qiu-shi; PAN Xue; ZHAO Qing-xia; WANG Xiao-kai

    2012-01-01

    Background Infusion phlebitis is the most common side effect of clinical intravenous drug therapy and several clinical studies have demonstrated that anisodamine can effectively prevent the occurrence of infusion phlebitis.This study was designed to investigate effects of anisodamine on the expressions of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in a rabbit model of infusion phlebitis and to analyze the mechanisms of anisodamine effect on the prevention and treatment of experimental infusion phlebitis.Methods Twenty-four specific pathogen-free male Japanese white rabbits were randomly assigned to the control group,the model group,the magnesium sulfate group and the anisodamine group.The rabbit model of infusion phlebitis,induced by intravenous administration,was established and expressions of VEGF and ICAM-1 were determined and contrasted with the control group treated with normal saline.We evaluated expression by histopathology,immunohistochemistry,reverse transcription-polymerase chain reaction,and Western blotting assay.Results Pathohistological changes of the model group were observed,such as loss of venous endothelial cells,inflammatory cell infiltration,edema and thrombus.The magnesium sulfate group and the anisodamine group showed significant protective effects on vascular congestion,inflammatory cell infiltration,proliferation,swelling of endothelium and perivascular hemorrhage.The model group showed the highest expressions of VEGF and ICAM-1 of the four groups (P<0.01).On the contrary,anisodamine alleviated the inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1 compared with the model group (P <0.01).There was no significant difference in the expressions of VEGF and ICAM-1 between the magnesium sulfate group and the anisodamine group (P >0.05).Conclusion Anisodamine alleviates inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1,and shows

  5. The membrane protein melanoma cell adhesion molecule (MCAM) is a novel tumor marker that stimulates tumorigenesis in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, J; Tang, X; Weng, W; Qiao, Y; Lin, J; Liu, W; Liu, R; Ma, L; Yu, W; Yu, Y; Pan, Q; Sun, F

    2015-11-19

    Yes-associated protein (YAP) is overexpressed and has an oncogenic role in hepatocellular carcinoma (HCC). However, whether membrane protein can serve not only as a tumor marker that reflects YAP function but also as a therapeutic target that stimulates tumorigenesis in HCC remains unknown. Here we report that the membrane protein melanoma cell adhesion molecule (MCAM) was under positive regulation by YAP and was highly elevated in HCC cells. Within the MCAM promoter, we found the presence of a cAMP Response Element (CRE; -32 to -25 nt), which is conserved among species and is essential for YAP- and CREB-dependent regulation. Moreover, the interaction between CREB and YAP at the CRE site was dependent on PTPIY-WW domain interactions. However, MCAM expression was low and could not be regulated by YAP in breast and colon cancer cells because of the low levels of the acetyltransferase p300. In HCC cells, high levels of p300 facilitated the binding of YAP to the MCAM promoter, which in turn enhanced histone acetylation and polymerase II recruitment through the dissociation of the deacetylase Sirt1. These results suggest that MCAM is an HCC-specific target of YAP. In clinical serum samples, we found that the serum levels of MCAM were highly elevated in patients with HCC compared with healthy controls and with patients with cirrhosis, hepatitis, colon cancer and breast cancer. MCAM levels were shown to be a slightly better indicator than serum alpha-fetoprotein for predicting HCC. We further demonstrated that MCAM is essential for the survival and transformation of HCC. Mechanistically, MCAM induced translation initiation and the transcriptional activities of c-Jun/c-Fos. In addition, AKT activation had an essential role in the MCAM-promoted binding of eukaryotic initiation factor 4E to c-Jun/c-Fos mRNA. In conclusion, we demonstrated that MCAM may be a potential tumor marker and therapeutic target for the diagnosis and treatment of HCC.

  6. Regulation of vascular cell adhesion molecule-1 in dental pulp cells by interleukin-1β: the role of prostanoids.

    Science.gov (United States)

    Chang, Mei-Chi; Lin, Li-Deh; Zwei-Ching Chang, Jenny; Huang, Chiung-Fang; Chuang, Fu-Hsiung; Lee, Jang-Jaer; Jeng, Po-Yuan; Wang, Tong-Mei; Jeng, Jiiang-Huei

    2012-06-01

    Vascular cell adhesion molecule (VCAM-1) plays a critical role in the inflammatory processes by stimulating the recruitment, extravasation, and migration of leukocytes. Its expression and regulation in the dental pulp is not well elucidated. Primary dental pulp cells were exposed to prostaglandin E(2) (PGE(2)), prostaglandin F(2α) (PGF(2α)), or interleukin 1β (IL-1β) with/without aspirin. VCAM-1 messenger RNA expression was analyzed by reverse transcriptase-polymerase chain reaction. Soluble VCAM-1 (sVCAM-1) in the culture medium was determined by enzyme-linked immunosorbent assay, and the number of viable cells was estimated by (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. IL-1β induced VCAM-1 gene expression of pulp cells. IL-1β also stimulated sVCAM-1 production. The IL-1β-induced sVCAM-1 production was not inhibited but rather enhanced by aspirin, a cyclooxygenase (COX) inhibitor. PGE(2) and PGF(2α) decreased the VCAM-1 expression and sVCAM-1 production of pulp cells. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), a mitogen-activated protein kinase kinase (MEK) inhibitor, attenuated IL-1β-induced sVCAM-1 production. However, no marked cytotoxicity was noted in these experimental conditions as analyzed by MTT assay. IL-1β may be involved in the pulpal inflammatory processes via stimulation of VCAM-1 expression and sVCAM-1 production. This event is not mediated by COX activation and prostanoid production but is associated with MEK signaling. PGE(2) and PGF(2α) may potentially regulate inflammatory processes by the inhibition of VCAM-1. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Evaluation of soluble junctional adhesion molecule-A as a biomarker of human brain endothelial barrier breakdown.

    Directory of Open Access Journals (Sweden)

    Axel Haarmann

    Full Text Available BACKGROUND: An inducible release of soluble junctional adhesion molecule-A (sJAM-A under pro-inflammatory conditions was described in cultured non-CNS endothelial cells (EC and increased sJAM-A serum levels were found to indicate inflammation in non-CNS vascular beds. Here we studied the regulation of JAM-A expression in cultured brain EC and evaluated sJAM-A as a serum biomarker of blood-brain barrier (BBB function. METHODOLOGY/PRINCIPAL FINDINGS: As previously reported in non-CNS EC types, pro-inflammatory stimulation of primary or immortalized (hCMEC/D3 human brain microvascular EC (HBMEC induced a redistribution of cell-bound JAM-A on the cell surface away from tight junctions, along with a dissociation from the cytoskeleton. This was paralleled by reduced immunocytochemical staining of occludin and zonula occludens-1 as well as by increased paracellular permeability for dextran 3000. Both a self-developed ELISA test and Western blot analysis detected a constitutive sJAM-A release by HBMEC into culture supernatants, which importantly was unaffected by pro-inflammatory or hypoxia/reoxygenation challenge. Accordingly, serum levels of sJAM-A were unaltered in 14 patients with clinically active multiple sclerosis compared to 45 stable patients and remained unchanged in 13 patients with acute ischemic non-small vessel stroke over time. CONCLUSION: Soluble JAM-A was not suited as a biomarker of BBB breakdown in our hands. The unexpected non-inducibility of sJAM-A release at the human BBB might contribute to a particular resistance of brain EC to inflammatory stimuli, protecting the CNS compartment.

  8. Activated endothelial interleukin-1beta, -6, and -8 concentrations and intercellular adhesion molecule-1 expression are attenuated by lidocaine.

    LENUS (Irish Health Repository)

    Lan, Wei

    2012-02-03

    Endothelial cells play a key role in ischemia reperfusion injury. We investigated the effects of lidocaine on activated human umbilical vein endothelial cell (HUVEC) interleukin (IL)-1beta, IL-6, and IL-8 concentrations and intercellular adhesion molecule-1 (ICAM-1) expression. HUVECs were pretreated with different concentrations of lidocaine (0 to 0.5 mg\\/mL) for 60 min, thereafter tumor necrosis factor-alpha was added at a concentration of 2.5 ng\\/mL and the cells incubated for 4 h. Supernatants were harvested, and cytokine concentrations were analyzed by enzyme-linked immunosorbent assay. Endothelial ICAM-1 expression was analyzed by using flow cytometry. Differences were assessed using analysis of variance and post hoc unpaired Student\\'s t-test where appropriate. Lidocaine (0.5 mg\\/mL) decreased IL-1beta (1.89 +\\/- 0.11 versus 4.16 +\\/- 1.27 pg\\/mL; P = 0.009), IL-6 (65.5 +\\/- 5.14 versus 162 +\\/- 11.5 pg\\/mL; P < 0.001), and IL-8 (3869 +\\/- 785 versus 14,961 +\\/- 406 pg\\/mL; P < 0.001) concentrations compared with the control. IL-1beta, IL-6, and IL-8 concentrations in HUVECs treated with clinically relevant plasma concentrations of lidocaine (0.005 mg\\/mL) were similar to control. ICAM-1 expression on lidocaine-treated (0.05 mg\\/mL) HUVECs was less than on controls (198 +\\/- 52.7 versus 298 +\\/- 50.3; Mean Channel Fluorescence; P < 0.001). Activated endothelial IL-1beta, IL-6, and IL-8 concentrations and ICAM-1 expression are attenuated only by lidocaine at concentrations larger than clinically relevant concentrations.

  9. Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Ohara; Takehiko Koji; Hiroshi Nagura; Shigeru Kohno; Hajime Isomoto; Chun-Yang Wen; Chieko Ejima; Masahiro Murata; Masanobu Miyazaki; Fuminao Takeshima; Yohei Mizuta; Ikuo Murata

    2003-01-01

    AIM: The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT). Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center, strongly associated with H pylori infection. The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG.METHODS: We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls. A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM1 and integrin β7. In simultaneous viewing of serial sections,the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated. We also performed immunostaining with anti-CD20, CD4, CD8 and CD68 antibodies to determine the lymphocyte subsets coexpressing integrin β7.RESULTS: Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection. Of note, the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls. Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates. Integrin β7-expressing mononuclear cells, mainly composed of CD20 and CD4 lymphocytes, were associated with vessels lined with MAdCAM-1-expressing endothelium.CONCLUSION: Our results suggest that the MAdCAM-1/integrin α4β7 homing system may participate in gastric inflammation in response to H pylori-infection and contributes to MALT formation, typically leading to the development of NG.

  10. Differential Expression of Extracellular Matrix and Adhesion Molecules in Fetal-Origin Amniotic Epithelial Cells of Preeclamptic Pregnancy.

    Science.gov (United States)

    Kim, Myung-Sun; Yu, Ji Hea; Lee, Min-Young; Kim, Ah Leum; Jo, Mi Hyun; Kim, MinGi; Cho, Sung-Rae; Kim, Young-Han

    2016-01-01

    Preeclampsia is a common disease that can occur during human pregnancy and is a leading cause of both maternal and neonatal morbidity and mortality. Inadequate trophoblast invasion and deficient remodeling of uterine spiral arteries are associated with preeclampsia (PE). The development of this syndrome is thought to be related to multiple factors. Recently, we isolated patient-specific human amniotic epithelial cells (AECs) from the placentas of 3 women with normal pregnancy and 3 with preeclamptic pregnancy. Since the characteristics of human AECs in PE are different from those in normal pregnancy, we sought to confirm the genes differentially expressed between preeclamptic pregnancy and normal pregnancy. Therefore, we performed transcriptome analysis to investigate the candidate genes associated with the possible pathophysiology of preeclampsia. Pathway analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) online resource. In this study, we selected a total of 12 pathways and focused on extracellular matrix-related and biological adhesion molecules. Using RT-PCR array and real-time PCR, we confirmed that COL16A1, ITGB2, and LAMA3 were significantly up-regulated, but ITGA1, ITGA3, ITGA6, MMP1, MMP3, MMP10 and MMP11 were significantly down-regulated in preeclamptic fetal origin cells. Taken together, we suggest that the genes and pathways identified here may be responsible for the occurrence and development of PE, and controlling their expression may play a role in communication with fetal-maternal placenta to keep normal pregnancy.

  11. Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1.

    Science.gov (United States)

    Heinrich, Garrett; Russo, Lucia; Castaneda, Tamara R; Pfeiffer, Verena; Ghadieh, Hilda E; Ghanem, Simona S; Wu, Jieshen; Faulkner, Latrice D; Ergün, Süleyman; McInerney, Marcia F; Hill, Jennifer W; Najjar, Sonia M

    2016-05-20

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1(-/-)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(-/-) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid β-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(-/-) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty-acid synthase activity could underlie altered energy balance in these mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

    Institute of Scientific and Technical Information of China (English)

    李春盛; 桂培春; 何新华

    2000-01-01

    Objeaive. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaeeharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasoue group.Macroscopic and histopathological e~aminatiom were performed and biological markers were measured for the lung specimem. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA. Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P < 0.01),demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasoue and rhubarb emfld decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P< 0.01, P < 0.05) ; the correslxmding pathologic changes of lung tissues and the biological markers of the lung injury were simifieantlv decreased or ameliorated. Conclusions. The increase of the expression d ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI.The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM-1 m

  13. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury.Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA.Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<0.01), demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<0.01, P<0.05); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated.Conclusions. The increase of the expression of ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM

  14. Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p

    Energy Technology Data Exchange (ETDEWEB)

    Broisat, A.; Riou, L.M.; Ardisson, V.; Fagret, D.; Ghezzi, C. [INSERM, U340, Radiopharmaceutiques Biocliniques, La Tronche (France); Universite de Grenoble, Saint Martin d' Heres (France); Boturyn, D.; Dumy, P. [Universite de Grenoble, Saint Martin d' Heres (France); LEDSS V - Ingenierie Moleculaire, CNRS UMR 5616, Saint Martin d' Heres (France)

    2007-06-15

    VCAM-1 plays a major role in the chronic inflammatory processes present in vulnerable atherosclerotic plaques. The residues 75-84 (B2702-p) and 84-75/75-84 (B2702-rp) of the major histocompatibility complex-1 (MHC-1) molecule B2702 were previously shown to bind specifically to VCAM-1. We hypothesised that radiolabelled B2702-p and B2702-rp might have potential for the molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) expression in atherosclerotic plaques. Preliminary biodistribution studies indicated that {sup 125}I-B2702-rp was unsuitable for in vivo imaging owing to extremely high lung uptake. {sup 123}I- or {sup 99m}Tc-labelled B2702-p was injected intravenously to Watanabe heritable hyperlipidaemic rabbits (WHHL, n = 6) and control animals (n = 6). After 180 min, aortas were harvested for ex vivo autoradiographic imaging, gamma-well counting, VCAM-1 immunohistology and Sudan IV lipid staining. Robust VCAM-1 immunostaining was observed in Sudan IV-positive and to a lesser extent in Sudan IV-negative areas of WHHL animals, whereas no expression was detected in control animals. Significant 2.9-fold and 1.9-fold increases in {sup 123}I-B2702-p and {sup 99m}Tc-B2702-p aortic-to-blood ratios, respectively, were observed between WHHL and control animals (p < 0.05). Tracer uptake on ex vivo images co-localised with atherosclerotic plaques. Image quantification indicated a graded increase in {sup 123}I-B2702-p and {sup 99m}Tc-B2702-p activities from control to Sudan IV-negative and to Sudan IV-positive areas, consistent with the observed pattern of VCAM-1 expression. Sudan IV-positive to control area tracer activity ratios were 17.0 {+-} 9.0 and 5.9 {+-} 1.8 for {sup 123}I-B2702-p and {sup 99m}Tc-B2702-p, respectively. Radiolabelled B2702-p is a potentially useful radiotracer for the molecular imaging of VCAM-1 in atherosclerosis. (orig.)

  15. ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules.

    Science.gov (United States)

    Cui, Hong-Xia; Wang, Honglan; Wang, Yuchun; Song, Juan; Tian, Hua; Xia, Chunhui; Shen, Yetong

    2016-12-01

    Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated. In the present study, we aimed to investigate the influence of ST3Gal III on key steps in the process of breast cancer metastasis. ST3Gal III-overexpressing and ST3Gal III-silenced breast cancer MDA-MB-231 cell lines were generated. They showed an increase or decrease in the tumor-associated antigen sialyl-Lewis X (SLeX). The E-selectin binding capacity of the transfectants was proportional to cell surface SLeX levels. Cell migration and invasion were positively correlated with ST3Gal III levels. Moreover, ST3Gal III expression modulated the protein expression of invasion-related molecules, including β1 integrin, matrix metalloproteinase (MMP)-2, MMP-9 and cyclooxygenase-2, which may account for the mechanism involved in the effects of ST3Gal III on breast cancer invasiveness. In conclusion, our findings in these novel models of ST3Gal III expression revealed a critical requirement for ST3Gal III in several steps of breast cancer metastasis. ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules. This study provides novel insights into the mechanisms underlying metastasis and suggests a new target for the effective drug treatment of breast cancer metastasis.

  16. Activation of nuclear factor-kappa B and cell adhesion molecule mRNA expression in duodenal mucosa of dogs with lymphocytic-plasmacytic enteritis.

    Science.gov (United States)

    Okanishi, Hiroki; Kabeya, Hidenori; Maruyama, Soichi; Kagawa, Yumiko; Watari, Toshihiro

    2013-08-15

    Lymphocytic-plasmacytic enteritis (LPE) is the most common form of inflammatory bowel disease (IBD) affecting the canine small intestine; however, the molecular basis of the pathogenesis remains unclear. It has recently been hypothesized that the primary defect is impaired innate immune function, as is the case for human IBD. Nuclear factor-kappa B (NFkappaB) plays a central role in innate immunity, and is a major transcriptional regulator of several proinflammatory cytokines, pattern recognition receptors (PRRs) such as toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors and cell adhesion molecules (CAMs). The purpose of this study was to evaluate, in the duodenal mucosa of 21 dogs with LPE and 8 control dogs, the degree of NFkappaB activity and the mRNA expression of two selected cytokines, nucleotide oligomerization domain two (NOD2) receptor and three selected CAMs, all of which are regulated by NFkappaB, using the electrophoretic mobility shift assay and real-time reverse transcription PCR. NFkappaB binding activity was significantly higher in the inflamed duodenal mucosa of the LPE dogs as compared to healthy controls. Furthermore, expression of mRNA for intercellular cell adhesion molecule 1 (ICAM-1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was significantly higher and vascular cell adhesion molecule 1 (VCAM-1) mRNA significantly lower in LPE dogs than in healthy controls. However, there was no significant difference in the mRNA levels for TNFα, IL1β and NOD2 between the two groups. These results suggest that NFkappaB and CAMs may play important roles in the pathogenesis of canine LPE. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Mild hypothermia effects on intercellular adhesion molecule-1 and serum interleukin-6 expression in brain tissues of a rat focal ischemia model

    Institute of Scientific and Technical Information of China (English)

    Shengqi Fu; Lei Yang; Shuling Zhang; Shilong Sun; Xingai Mao

    2008-01-01

    BACKGROUND: Previous studies have confirmed the neuroprotective effect of mild hypothermia on ischemic brain injury.OBJECTIVE: To investigate the effects of mild hypothermia on intercellular adhesion molecule-1 expression and serum interleukin-6 levels in ischemic brain tissues of focal brain ischemia rats, and to explore the neuroprotective effects of mild hypothermia on ischemic brain injury.DESIGN, TIME AND SETTING: A randomized, controlled, neurobiological experiment was performed at the Central Laboratory, First Affiliated Hospital, Xinxiang Medical College, China from February to July 2006.MATERIALS: Thirty healthy, adult, Sprague Dawley rats were used to establish middle cerebral artery occlusion models using the suture method. The immunohistochemistry (streptavidin-biotin-peroxidase complex method) kit was purchased from Boster, China. Interleukin-6 radioimmunoassay was supplied by Institute of Radioimmunity, Technology Development Center, General Hospital of Chinese PLA. METHODS: The rats were equally and randomly assigned into mild hypothermia and control groups, and middle cerebral artery occlusion models were established. The rectal temperature was maintained at (37 ± 0.5)℃ in the control group. In the mild hypothermia group, the rectal temperature was maintained at (33±1)℃.MAIN OUTCOME MEASURES: At 12 hours after model establishment, the ischemic brain hemispheres were coronally sliced at the level of the optic chiasm. The number of intercellular adhesion molecule- 1 -positive vessels per high-power field was observed with an optical microscope. Serum interleukin-6 levels were measured by radioimmunoassay.RESULTS: Compared with the control group, intercellular adhesion molecule-I and serum interleukin-6 expressions were significantly decreased in ischemic brain tissues of the mild hypothermia group (P < 0.01).CONCLUSION: Mild hypothermia exhibits a neuroprotective effect by reducing serum interleukin-6 and intercellular adhesion molecule- 1

  18. Fibrolamellar carcinoma of the liver: composition of the extracellular matrix and expression of cell-matrix and cell-cell adhesion molecules.

    Science.gov (United States)

    Scoazec, J Y; Flejou, J F; D'Errico, A; Fiorentino, M; Zamparelli, A; Bringuier, A F; Feldmann, G; Grigioni, W F

    1996-11-01

    We have analyzed the composition of the tumor stroma and the expression of cell-matrix and cell-cell adhesion molecules in 11 cases of fibrolamellar carcinoma of the liver (FLC), in comparison with 34 cases of hepatocellular carcinoma and 8 cases of focal nodular hyperplasia. Fibrolamellar carcinoma was characterized by the presence of large amounts of tenascin in tumor stroma and by the scarce expression of basement membrane components at the contact of neoplastic clusters. Like normal hepatocytes, neoplastic cells constantly expressed the alpha1 integrin chain, lacked the beta4 integrin chain, and coexpressed E-cadherin and the hepatocyte N-related cadherin. Abnormalities in the expression of cell adhesion molecules, including altered cadherin expression, alphaV integrin chain induction, and CD44 expression, were detected in the majority of cases. The composition of the tumor stroma and the pattern of expression of cell adhesion molecules in fibrolamellar carcinoma were reminiscent of those observed in grade III and grade IV hepatocellular carcinomas. Our results therefore show that, despite its slow local growth and good prognosis, fibrolamellar carcinoma expresses many characteristics usually associated with clinically aggressive malignancies. Further studies are needed to identify the factors responsible for the apparent dissociation between clinical behavior and biological characteristics in this tumor.

  19. The Receptor for Advanced Glycation End-Products (RAGE) Is Only Present in Mammals, and Belongs to a Family of Cell Adhesion Molecules (CAMs)

    Science.gov (United States)

    Sessa, Luca; Gatti, Elena; Zeni, Filippo; Antonelli, Antonella; Catucci, Alessandro; Koch, Michael; Pompilio, Giulio; Fritz, Günter

    2014-01-01

    The human receptor for advanced glycation endproducts (RAGE) is a multiligand cell surface protein belonging to the immunoglobulin superfamily, and is involved in inflammatory and immune responses. Most importantly, RAGE is considered a receptor for HMGB1 and several S100 proteins, which are Damage-Associated Molecular Pattern molecules (DAMPs) released during tissue damage. In this study we show that the Ager gene coding for RAGE first appeared in mammals, and is closely related to other genes coding for cell adhesion molecules (CAMs) such as ALCAM, BCAM and MCAM that appeared earlier during metazoan evolution. RAGE is expressed at very low levels in most cells, but when expressed at high levels, it mediates cell adhesion to extracellular matrix components and to other cells through homophilic interactions. Our results suggest that RAGE evolved from a family of CAMs, and might still act as an adhesion molecule, in particular in the lung where it is highly expressed or under pathological conditions characterized by an increase of its protein levels. PMID:24475194

  20. Oil-Infused Superhydrophobic Silicone Material for Low Ice Adhesion with Long-Term Infusion Stability.

    Science.gov (United States)

    Yeong, Yong Han; Wang, Chenyu; Wynne, Kenneth J; Gupta, Mool C

    2016-11-23

    A new approach for anti-icing materials was created to combat the effects of ice accretion and adhesion. The concept combines the strengths of individual characteristics for low ice adhesion based on elasticity, superhydrophobicity, and slippery liquid infused porous surfaces (SLIPS) for an optimal combination of high water repellency and ice-phobicity. This was achieved by replicating microtextures from a laser-irradiated aluminum substrate to an oil-infused polydimethylsiloxane (PDMS) elastomer, the result of which is a flexible, superhydrophobic, and lubricated material. This design provides multiple strategies of icing protection through high water repellency to retard ice accretion and with elasticity and oil infusion for low ice adhesion in a single material. Studies showed that an infusion of silicone oils with viscosity at 100 cSt and below 8 wt % in PDMS solution is sufficient to reduce the ice shear strength to an average of 38 kPa while maintaining contact angles and roll-off angles of above 150° and below 10°, respectively. This ice-adhesion value is a ∼95% reduction from a bare aluminum surface and ∼30% reduction from a microtextured, superhydrophobic PDMS material without oil infusion. In addition, three-month aging studies showed that the wetting and ice-adhesion performance of this material did not significantly degrade.

  1. Reduction of Adhesion Molecule Production and Alteration of eNOS and Endothelin-1 mRNA Expression in Endothelium by Euphorbia hirta L. through Its Beneficial β-Amyrin Molecule

    Directory of Open Access Journals (Sweden)

    Mei Fen Shih

    2014-07-01

    Full Text Available The inflammatory reaction in large blood vessels involves up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin, soluble vascular cell adhesion molecule (sVCAM-1, and soluble intercellular adhesion molecule (sICAM-1. These vascular dysfunctions are associated with the development of atherosclerosis. β-Amyrin, an active component of Euphorbia hirta L., has potent anti-inflammatory effects. So far, its preventive effects against the expression of inflammatory mediator-induced adhesion molecules have not been investigated. Endothelial cells (SVEC4-10 cell line were treated with 50% RAW conditioned media (i.e., normal SVEC4-10 culture media contains 50% of lipopolysaccharide-activated macrophage culture media without or with β-amyrin (0.6 and 0.3 µM. The production levels of E-selectin, sICAM-1, and sVCAM-1 in the SVEC4-10 cells were measured with ELISA assay kits. Under the same treatment conditions, expression of endothelin (ET-1 and endothelial type of NO synthase (eNOS mRNA were analyzed by RT-PCR and agarose gel. With β-amyrin, the 50% RAW conditioned media-induced E-selectin, sICAM-1, and sVCAM-1 levels as well as ET-1 gene expression were all suppressed. β-Amyrin treatment also restored the 50% RAW conditioned media-suppressed eNOS mRNA expression. These data indicate that β-amyrin is potentially useful in preventing chronic inflammation-related vascular diseases.

  2. Considerable improvement in the stability of solution processed small molecule OLED by annealing

    Energy Technology Data Exchange (ETDEWEB)

    Mao Guilin [Key Laboratory of Photonics Technology for Information, Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic and Information Engineering, Xi' an Jiaotong University, Xi' an, 710049 (China); Wu Zhaoxin, E-mail: zhaoxinwu@mail.xjtu.edu.cn [Key Laboratory of Photonics Technology for Information, Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic and Information Engineering, Xi' an Jiaotong University, Xi' an, 710049 (China); He Qiang [Key Laboratory of Photonics Technology for Information, Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic and Information Engineering, Xi' an Jiaotong University, Xi' an, 710049 (China); Department of UAV, Wuhan Ordnance Noncommissioned Officers Academy, Wuhan, 430075 (China); Jiao Bo; Xu Guojin; Hou Xun [Key Laboratory of Photonics Technology for Information, Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic and Information Engineering, Xi' an Jiaotong University, Xi' an, 710049 (China); Chen Zhijian; Gong Qihuang [State Key Laboratory for Mesoscopic Physics and Department of Physics, Peking University, Beijing, 100871 (China)

    2011-06-15

    We investigated the annealing effect on solution processed small organic molecule organic films, which were annealed with various conditions. It was found that the densities of the spin-coated (SC) films increased and the surface roughness decreased as the annealing temperature rose. We fabricated corresponding organic light emitting diodes (OLEDs) by spin coating on the same annealing conditions. The solution processed OLEDs show the considerable efficiency and stability, which were prior or equivalent to the vacuum-deposited (VD) counterparts. Our research shows that annealing process plays a key role in prolonging the lifetime of solution processed small molecule OLEDs, and the mechanism for the improvement of the device performance upon annealing was also discussed.

  3. Exploiting Transient Protein States for the Design of Small-Molecule Stabilizers of Mutant p53

    Science.gov (United States)

    Joerger, Andreas C.; Bauer, Matthias R.; Wilcken, Rainer; Baud, Matthias G.J.; Harbrecht, Hannes; Exner, Thomas E.; Boeckler, Frank M.; Spencer, John; Fersht, Alan R.

    2015-01-01

    Summary The destabilizing p53 cancer mutation Y220C creates an extended crevice on the surface of the protein that can be targeted by small-molecule stabilizers. Here, we identify different classes of small molecules that bind to this crevice and determine their binding modes by X-ray crystallography. These structures reveal two major conformational states of the pocket and a cryptic, transiently open hydrophobic subpocket that is modulated by Cys220. In one instance, specifically targeting this transient protein state by a pyrrole moiety resulted in a 40-fold increase in binding affinity. Molecular dynamics simulations showed that both open and closed states of this subsite were populated at comparable frequencies along the trajectories. Our data extend the framework for the design of high-affinity Y220C mutant binders for use in personalized anticancer therapy and, more generally, highlight the importance of implementing protein dynamics and hydration patterns in the drug-discovery process. PMID:26636255

  4. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    Directory of Open Access Journals (Sweden)

    Aljona Gaiko-Shcherbak

    Full Text Available The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  5. Stability of guest molecules in urea canal complexes by canal polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Yoshii, Fumio; Makuuchi, Keizo [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1995-03-01

    It was found that various organic materials are attracted into urea canal by hexanediol diacrylate (HDDA) and long chain compounds. This means that materials which does not form complex by itself are induced in canal by HDDA and long chain compounds. To include with stability perfumes, insecticides, attractants and repellents in urea canal, leaf alcohol was used as a model compound for guest molecules in the canal. The leaf alcohol from the canal released gradually over many days and the release was inhibited for 15 days by long chain compounds and for 30 days by polymerized HDDA after irradiation. After releasing, the leaf alcohol in the canal remained 25 % stable for long chain compounds and 40 % for polymerized HDDA. The dose required for stabilization of leaf alcohol in the urea canal by canal polymerization of HDDA was 30 kGy. (author).

  6. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Institute of Scientific and Technical Information of China (English)

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  7. Stability of metal organic frameworks and interaction of small gas molecules in these materials

    Science.gov (United States)

    Tan, Kui

    The work in this dissertation combines spectroscopy ( in-situ infrared absorption and Raman), powder X-ray diffraction and DFT calculations to study the stability of metal organic frameworks materials (MOFs) in the presence of water vapor and other corrosive gases (e.g., SO 2, NO2 NO), and the interaction and competitive co-adsorption of several gases within MOFs by considering two types of prototypical MOFs: 1) a MOF with saturated metal centers based on paddlewheel secondary building units: M(bdc)(ted)0.5 [M=Cu, Zn, Ni, Co, bdc = 1,4-benzenedicarboxylate, ted = triethylenediamine], and 2) a MOF with unsaturated metal centers: M2(dobdc) [M=Mg2+, Zn2+, Ni2+, Co2+ and dobdc = 2,5-dihydroxybenzenedicarboxylate]. We find that the stability of MOFs to water vapor critically depends on their structure and the specific metal cation in the building units. For M(bdc)(ted)0.5, the metal-bdc bond is the most vulnerable for Cu(bdc)(ted)0.5, while the metal-ted bond is first attacked for the Zn and Co analogs. In contrast, Ni(bdc)(ted)0.5 remains stable under the same conditions. For M2(dobdc), or MOF-74, the weak link is the dobdc-metal bond. The water molecule is dissociatively adsorbed at the metal-oxygen group with OH adsorption directly on the metal center and H adsorption on the bridging O of the phenolate group in the dobdc linker. Other technologically important molecules besides water, such as NO, NO2, SO2, tend to poison M2(dobdc) through dissociative or molecular adsorption onto the open metal sites. A high uptake SO2 capacity was measured in M(bdc)(ted)0.5, attributed to multipoint interactions between the guest SO2 molecule and the MOF host. In the case of competitive co-adsorption between CO2 and other small molecules, we find that binding energy alone is not a good indicator of molecular site occupation within the MOF (i.e., it cannot successfully predict and evaluate the displacement of CO2 by other molecules). Instead, we show that the kinetic barrier for the

  8. Dock mediates Scar- and WASp-dependent actin polymerization through interaction with cell adhesion molecules in founder cells and fusion-competent myoblasts.

    Science.gov (United States)

    Kaipa, Balasankara Reddy; Shao, Huanjie; Schäfer, Gritt; Trinkewitz, Tatjana; Groth, Verena; Liu, Jianqi; Beck, Lothar; Bogdan, Sven; Abmayr, Susan M; Önel, Susanne-Filiz

    2013-01-01

    The formation of the larval body wall musculature of Drosophila depends on the asymmetric fusion of two myoblast types, founder cells (FCs) and fusion-competent myoblasts (FCMs). Recent studies have established an essential function of Arp2/3-based actin polymerization during myoblast fusion, formation of a dense actin focus at the site of fusion in FCMs, and a thin sheath of actin in FCs and/or growing muscles. The formation of these actin structures depends on recognition and adhesion of myoblasts that is mediated by cell surface receptors of the immunoglobulin superfamily. However, the connection of the cell surface receptors with Arp2/3-based actin polymerization is poorly understood. To date only the SH2-SH3 adaptor protein Crk has been suggested to link cell adhesion with Arp2/3-based actin polymerization in FCMs. Here, we propose that the SH2-SH3 adaptor protein Dock, like Crk, links cell adhesion with actin polymerization. We show that Dock is expressed in FCs and FCMs and colocalizes with the cell adhesion proteins Sns and Duf at cell-cell contact points. Biochemical data in this study indicate that different domains of Dock are involved in binding the cell adhesion molecules Duf, Rst, Sns and Hbs. We emphasize the importance of these interactions by quantifying the enhanced myoblast fusion defects in duf dock, sns dock and hbs dock double mutants. Additionally, we show that Dock interacts biochemically and genetically with Drosophila Scar, Vrp1 and WASp. Based on these data, we propose that Dock links cell adhesion in FCs and FCMs with either Scar- or Vrp1-WASp-dependent Arp2/3 activation.

  9. Relationship of cardiac arrhythmias to myocar- dial remodeling and expression of adhesion molecules in patients with mitral valve prolapse

    Directory of Open Access Journals (Sweden)

    A.V. Yagoda

    Conclusion. Myocardial remodeling and dysregulation of cell adhesion proteins are recorded in young patients with MVP and arrhythmias. Relaionship of severity of arrhythmic syndrome to myocardial remodeling and VCAM-1 level was revealed.

  10. Genetic analysis of beta1 integrin function: confirmed, new and revised roles for a crucial family of cell adhesion molecules

    DEFF Research Database (Denmark)

    Brakebusch, C; Hirsch, E; Potocnik, A

    1997-01-01

    Integrins are heterodimeric cell adhesion proteins connecting the extracellular matrix to the cytoskeleton and transmitting signals in both directions. These integrins are suggested to be involved in many different biological processes such as growth, differentiation, migration, and cell death...

  11. Serum inter-cellular adhesion molecule 1 is an early marker of diagnosis and prediction of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Hai-Hang Zhu; Lin-Lin Jiang

    2012-01-01

    AIM:To determine if serum inter-cellular adhesion molecule 1 (ICAM-1) is an early marker of the diagnosis and prediction of severe acute pancreatitis (SAP)within 24 h of onset of pain,and to compare the sensitivity,specificity and prognostic value of this test with those of acute physiology and chronic health evaluation (APACHE) Ⅱ score and interleukin-6 (IL-6).METHODS:Patients with acute pancreatitis (AP) were divided into two groups according to the Ranson's criteria:mild acute pancreatitis (MAP) group and SAP group.Serum ICAM-1,APACHE Ⅱ and IL-6 levels were detected in all the patients.The sensitivity,specificity and prognostic value of the ICAM-1,APACHE Ⅱ score and IL-6 were evaluated.RESULTS:The ICAM-1 level in 36 patients with SAP within 24 h of onset of pain was increased and was significantly higher than that in the 50 patients with MAP and the 15 healthy volunteers (P < 0.01).The ICAM-1 level (25 ng/mL) was chosen as the optimum cutoff to distinguish SAP from MAP,and the sensitivity,specificity,positive predictive value,negative predictive value (NPV),positive likelihood ratio and negative likelihood ratio were 61.11%,71.42%,0.6111,0.7142,2.1382 and 0.5445,respectively.The area under the curve demonstrated that the prognostic accuracy of ICAM-1 (0.712) was similar to the APACHE-Ⅱ scoring system (0.770) and superior to IL-6 (0.508) in distinguishing SAP from MAP.CONCLUSION:ICAM-1 test is a simple,rapid and reliable method in clinical practice.It is an early marker of diagnosis and prediction of SAP within the first 24 h after onset of pain or on admission.As it has a relatively low NPV and does not allow it to be a stand-alone test for the diagnosis of AP,other conventional diagnostic tests are required.

  12. Soluble intercellular adhesion molecule-1, D-lactate and diamine oxidase in patients with inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Wei-Bing Song; Yong-Hui Lv; Zhen-Shu Zhang; Ya-Nan Li; Li-Ping Xiao; Xin-Pei Yu; Yuan-Yuan Wang; Hong-Li Ji; Li Ma

    2009-01-01

    AIM: To study the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), plasma D-lactate and diamine oxidase (DAO) in patients with inflammatory bowel disease (IBD), and the potential clinical significance.METHODS: Sixty-nine patients with IBD and 30 healthy controls were included in this study. The concentration of sICAM-1 was detected with enzyme-linked immunosorbent assay, the level of D-lactate and DAO was measured by spectroscopic analysis, and the number of white blood cells (WBC) was determined by routine procedure.RESULTS: The levels of sICAM-l, DAO, and WBC in IBD patients were significantly higher than those in the control group ( P < 0.01). sICAM-l in IBD patients was found to be closely related to the levels of DAO and D-lactate (212.94 ± 69.89 vs 6.35 ± 2.35, P = 0.000),DAO 212.94 ± 69.89 vs 8.65 ± 3.54, P = 0.000) and WBC (212.94 ± 69.89 vs 7.40 ± 2.61, P = 0.000), but no significant difference was observed between patients with ulcerative colitis and patients with Crohn's disease.The post-treatment levels of sICAM-l, D-lactate and WBC were significantly lower than before treatment (sICAM-l 206.57 ± 79.21 vs 146.21 ± 64.43, P = 0.000),(D-lactate 1.46 ± 0.94 vs 0.52 ± 0.32, P = 0.000) and (WBC 7.24 ± 0.2.33 vs 5.21 ± 3.21, P = 0.000).CONCLUSION: sICAM-1, D-lactate and DAO are closely related to the specific conditions of IBD, and thus could be used as a major diagnostic index.

  13. The influence of TNF-alpha on concentration of soluble adhesion molecules in cultures of HT-29 cells exposed to inositol hexaphosphate.

    Science.gov (United States)

    Parfiniewicz, Beata; Pendzich, Joanna; Kapral, Małgorzata; Bednarek, Ilona; Weglarz, Ludmiła

    2012-01-01

    The latest studies suggest that adhesion molecules are involved in the arising of malignant changes and in distant metastasis induction. The soluble forms of several adhesion molecules, have recently emerged as novel and potentially useful tumor markers. Among a number of identified, high interest wake soluble molecules similar to the immunoglobulin -- soluble intercellular adhesion molecules-1 (sICAM-1) and soluble E-cadherin (sE-cadherin). In the present work, the authors concentrate on one tumor type, colorectal carcinoma, in which distant metastases, are the main cause of failure, in spite of surgical curing of the primary tumor. It is known that TNF-alpha (tumor necrosis factor - alpha) serum concentration of patients with cancer is raised. The changes in soluble adhesion molecules concentrations in serum and others fluids, could be modulated by many different factors affecting cancer cells. In the case of colon cancer one of the factors is a high-fiber diet, containing an anti-cancer chemical, inositol hexaphosphate (IP6). The aim of this study was to estimate the influence of TNF-alpha on the concentration of sICAM-1 and sE-cadherin in the microenvironment of HT-29 malignant epithelial colorectal cells stimulated with IP6. Additonally, adhesive property of HT-29 human colorectal cancer cell line to collagen I was estimated. The HT-29 cells were treated with TNF-alpha (10 ng/mL and 100 ng/mL - estimation of sICAM and sE-cadherin concentration; 100 ng/mL - adhesion assay), IP6 (0.5 mM, 1.0 mM, 2.0 mM) and TNF-alpha in combination with IP6. The level of sICAM-1 and sE-cadherin in cultures of HT-29 cells was measured by enzyme-linked immunosorbent assay (R&D Systems), and adhesion of the cells to collagen I was investigated by Cyquant Proliferation Assay Kit. The present findings demonstrate that TNF-alpha and inositol hexaphosphate have an effect on the sICAM-1 and sE-cadherin concentration in cultures of HT-29 cells. IP6 at a concentration of 2.0 mM induced a

  14. Polysialic acid modification of the synaptic cell adhesion molecule SynCAM 1 in human embryonic stem cell-derived oligodendrocyte precursor cells

    Directory of Open Access Journals (Sweden)

    Sebastian Werneburg

    2015-05-01

    Full Text Available Oligodendrocyte precursor cells (OPCs are the progenitors of myelinating oligodendrocytes in brain development and repair. Successful myelination depends on the control of adhesiveness during OPC migration and axon contact formation. The decoration of cell surface proteins with the glycan polysialic acid (polySia is a key regulatory element of OPC interactions during development and under pathological conditions. By far the major protein carrier of polySia is the neural cell adhesion molecule NCAM, but recently, polysialylation of the synaptic cell adhesion molecule SynCAM 1 has been detected in the developing mouse brain. In mice, polySia-SynCAM 1 is associated with cells expressing NG2, a marker of a heterogeneous precursor cell population, which is the primary source for oligodendrocytes in development and myelin repair but can also give rise to astrocytes and possibly neurons. It is not yet clear if polySia-SynCAM 1 is expressed by OPCs and its occurrence in humans is elusive. By generating uniform human embryonic stem cell-derived OPC cultures, we demonstrate that polySia is present on human OPCs but down-regulated during differentiation into myelin basic protein-positive oligodendrocytes. PolySia on NCAM resides on the isoforms NCAM-180 and NCAM-140, and SynCAM 1 is identified as a novel polySia acceptor in human OPCs.

  15. Amino acid sequences mediating vascular cell adhesion molecule 1 binding to integrin alpha 4: homologous DSP sequence found for JC polyoma VP1 coat protein

    Directory of Open Access Journals (Sweden)

    Michael Andrew Meyer

    2013-07-01

    Full Text Available The JC polyoma viral coat protein VP1 was analyzed for amino acid sequences homologies to the IDSP sequence which mediates binding of VLA-4 (integrin alpha 4 to vascular cell adhesion molecule 1. Although the full sequence was not found, a DSP sequence was located near the critical arginine residue linked to infectivity of the virus and binding to sialic acid containing molecules such as integrins (3. For the JC polyoma virus, a DSP sequence was found at residues 70, 71 and 72 with homology also noted for the mouse polyoma virus and SV40 virus. Three dimensional modeling of the VP1 molecule suggests that the DSP loop has an accessible site for interaction from the external side of the assembled viral capsid pentamer.

  16. Amino Acid Sequences Mediating Vascular Cell Adhesion Molecule 1 Binding to Integrin Alpha 4: Homologous DSP Sequence Found for JC Polyoma VP1 Coat Protein.

    Science.gov (United States)

    Meyer, Michael Andrew

    2013-01-01

    The JC polyoma viral coat protein VP1 was analyzed for amino acid sequences homologies to the IDSP sequence which mediates binding of VLA-4 (integrin alpha 4) to vascular cell adhesion molecule 1. Although the full sequence was not found, a DSP sequence was located near the critical arginine residue linked to infectivity of the virus and binding to sialic acid containing molecules such as integrins (3). For the JC polyoma virus, a DSP sequence was found at residues 70, 71 and 72 with homology also noted for the mouse polyoma virus and SV40 virus. Three dimensional modeling of the VP1 molecule suggests that the DSP loop has an accessible site for interaction from the external side of the assembled viral capsid pentamer.

  17. Synthesis of ferrite nanocrystals stabilized by ionic-liquid molecules through a thermal decomposition route.

    Science.gov (United States)

    Zhang, Yu; Liu, Dapeng; Wang, Xiao; Song, Shuyan; Zhang, Hongjie

    2011-01-17

    A series of M(x) Fe(3-x) O(4) (M=Fe, Co, Ni, Zn; 0≤x≤1) ferrite nanocrystals stabilized by ionic-liquid molecules have been successfully synthesized through a thermal decomposition route. Instead of the widely used long-chain lipid surfactants and high-boiling solvents, the ionic-liquid molecules not only played the role of surfactants, but also served as reaction and dispersion media simultaneously in the preparation of ferrite nanocrystals. Due to their good fluidity under magnetic fields and high ionic conductivity, the ionic-liquid molecules and M(x) Fe(3-x) O(4) ferrite nanocrystal-based conducting ferrofluids were successfully used as electrolytes in an AC circuit. The open or closed state of the circuit was directly controlled by moving a permanent magnet so as to tune the position of the ferrofluids, and consequently, resulted in the "off" or "on" state of the four indicative yellow-light-emitting diodes. These results demonstrate that the conducting ferrofluids successfully play the role of "magnetic switch".

  18. Transfected HEK293 Cells Expressing Functional Recombinant Intercellular Adhesion Molecule 1 (ICAM-1) - A Receptor Associated with Severe Plasmodium falciparum Malaria

    DEFF Research Database (Denmark)

    Bengtsson, Anja; Joergensen, Louise; Barbati, Zachary R;

    2013-01-01

    Intercellular adhesion molecule 1 (ICAM-1) is a membrane-bound glycoprotein expressed on endothelial cells and cells of the immune system. Human ICAM-1 mediates adhesion and migration of leucocytes, and is implicated in inflammatory pathologies, autoimmune diseases and in many cancer processes....... Additionally, ICAM-1 acts as receptor for pathogens like human rhinovirus and Plasmodium falciparum malaria parasites. A group of related P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains, the DBLβ, mediates ICAM-1 binding of P. falciparum-infected erythrocytes. This ICAM‑1-binding phenotype has...... as vaccine candidates and go into clinical trials. Such studies require availability of functional recombinant ICAM-1 in large quantities. In this study, we compared recombinant ICAM-1 expressed in HEK293 and COS-7 cells with mouse myeloma NS0 ICAM-1 purchased from a commercial vendor in terms of protein...

  19. Davallia bilabiata inhibits TNF-α-induced adhesion molecules and chemokines by suppressing IKK/NF-kappa B pathway in vascular endothelial cells.

    Science.gov (United States)

    Yang, Rong-Chi; Chang, Cheng-Chieh; Sheen, Jer-Ming; Wu, Hsiao-Ting; Pang, Jong-Hwei S; Huang, Sheng-Teng

    2014-01-01

    Davallia bilabiata (D. bilabiata) is also called GuSuiBu in Taiwan and is used as a substitute for Drynaria fortunei J. Sm. It is often used for trauma and bone repair. The inhibitory effect of D. bilabiata on inflammatory activity has not been reported. In the present study, we aimed to study the mechanism of anti-inflammation of D. bilabiata on the adhesion of leukocytes to vascular endothelial cells. The results showed that D. bilabiata, at concentrations without cytotoxic effect, inhibited the adhesion of monocytes (THP-1) to the TNF-α-stimulated human umbilical vascular endothelial cells (HUVECs). D. bilabiata suppressed the expression of the adhesion molecules ICAM, VCAM, and E-selectin at both the mRNA and protein level. In addition, both of the TNF-α-induced mRNA and protein expression of chemokines including fractalkine/CX3CL1, MCP-1 and RANTES as well as the level of secreted soluble fractalkine were decreased by D. bilabiata. We also verified that D. bilabiata inhibited the TNF-α-induced nuclear translocation of NF-κB through the inhibitory process on the TNF-α-activated phosphorylation of IKKα, IKKβ, IκB and NF-κB. All together, we concluded that the D. bilabiata affected the canonical pathway of TNF-α-induced NF-κB activation and down-regulated cell adhesion molecules and chemokine expression through inhibition of the NF-κB/IκBα/IKK signaling pathway. These findings strongly indicated that D. bilabiata might be a promising alternative/adjunct treatment for inflammatory diseases, such as rheumatoid arthritis and osteoarthritis.

  20. Lanthanum Chloride Inhibits LPS Mediated Expressions of Pro-Inflammatory Cytokines and Adhesion Molecules in HUVECs: Involvement of NF-κB-Jmjd3 Signaling

    Directory of Open Access Journals (Sweden)

    Xia Chen

    2017-07-01

    Full Text Available Background/Aims: To investigate the regulation of LaCl3 on lipopolysaccharides (LPS-induced pro-inflammatory cytokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs. Methods: Primary cultured HUVECs were pretreated with 2.5 µM LaCl3 for 30 min followed by 1 µg/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-κB/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-κB/p65, Jmjd3, and H3K27me3 to gene promoter regions was determined by ChIP-qPCR. Results: LaCl3 exhibited no cytotoxic effects to primary HUVECs at concentrations ≤ 50 µM. LPS-mediated TNF-α, IL-1β, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-κB/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl3. Furthermore, LaCl3 treatment significantly impaired LPS-induced enrichment of NF-κB/p65 to the promoter regions of TNF-α, MMP-9, IL-1β, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-α, MMP-9, IL-1β, and IL-6. H3K27me3 abundance in the promoter regions of TNF-α and ICAM-1 increased significantly in following LaCl3 treatment. Conclusion: LaCl3 inhibits pro-inflammatory cytokine and adhesion molecule expressions induced by LPS in HUVECs. NF-κB and histone demethylase Jmjd3 are involved in this effect.

  1. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    Science.gov (United States)

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.

  2. [Expression of adhesion molecules on CD34+ cells of BM and PB stem cell samples during high-dose chemotherapy combined with transplantation of autologous PB stem cells].

    Science.gov (United States)

    Liu, Peng; Han, Xiao-Hong; Shi, Yuan-Kai; He, Xiao-Hui; Yang, Cheng; Ai, Bin

    2004-12-01

    This study was aimed to investigate the expressions of adhesion molecules such as CD54, CD49d and CD62L by CD34(+) cells sampled from different stages of bone marrow (BM) and peripheral blood (PB) before/after G-CSF mobilization and after transplantation through the direct labeling with three colour-immunofluorescence and flow cytometry, and to explore the differences in expression of adhesion molecules on CD34(+) cells from different origins and their clinical significance. Mononuclear cells collected from BM and PB before mobilization, after collection of stem cells and hematopoietic recostruction of BM at the end of transplantation were marked with CD54-FITC, CD49d-FITC and CD62L-FITC separately, as well as CD34-PE and CD45PerCE. 3-color fluorescene analysis was carried out by FACS. The expression differences of CD34(+) and adhesion molecules between BM and APBSC were compared. The results showed that expression differences of CD54, CD49d and cd62Lon CD34(+) cells belore mobilization, after collection and reconstraction of transplantation were not statiscally significant, the difference of CD54, CD49d and CD62L on CD34(+) between 1st and 2nd collections of hematopoietic stem cells also were not statiscally significant. In the collected APBSC, the expression level of CD34(+) CD49d(+) was significantly lower than those in BM before mobilization (P = 0.001). It is concluded that the method of chemotherapy combined with G-CSF mobilization can down-regulate CD49d expression in BM CD34(+) cells, thus can mobilize and move theirs into peripheral blood. After the reconstitution by transplantation, the expression of CD49d on CD34(+) cells tends to normal, the clinical significance needs to be elucidated by accumulation of much more cases.

  3. Neural Cell Adhesion Molecule-Associated Polysialic Acid Regulates Synaptic Plasticity and Learning by Restraining the Signaling through GluN2B-Containing NMDA Receptors

    Science.gov (United States)

    Kochlamazashvili, Gaga; Senkov, Oleg; Grebenyuk, Sergei; Robinson, Catrina; Xiao, Mei-Fang; Stummeyer, Katharina; Gerardy-Schahn, Rita; Engel, Andreas K.; Feig, Larry; Semyanov, Alexey; Suppiramaniam, Vishnu; Schachner, Melitta; Dityatev, Alexander

    2017-01-01

    The neural cell adhesion molecule (NCAM) is the predominant carrier of α2,8 polysialic acid (PSA) in the mammalian brain. Abnormalities in PSA and NCAM expression are associated with schizophrenia in humans and cause deficits in hippocampal synaptic plasticity and contextual fear conditioning in mice. Here, we show that PSA inhibits opening of recombinant NMDA receptors composed of GluN1/2B (NR1/NR2B) or GluN1/2A/2B (NR1/NR2A/NR2B) but not of GluN1/2A (NR1/NR2A) subunits. Deficits in NCAM/PSA increase GluN2B-mediated transmission and Ca2+ transients in the CA1 region of the hippocampus. In line with elevation of GluN2B-mediated transmission, defects in long-term potentiation in the CA1 region and contextual fear memory in NCAM/PSA-deficient mice are abrogated by application of a GluN2B-selective antagonist. Furthermore, treatment with the glutamate scavenger glutamic-pyruvic transaminase, ablation of Ras-GRF1 (a mediator of GluN2B signaling to p38 MAPK), or direct inhibition of hyperactive p38 MAPK can restore impaired synaptic plasticity in brain slices lacking PSA/NCAM. Thus, PSA carried by NCAM regulates plasticity and learning by inhibition of the GluN2B-Ras-GRF1-p38 MAPK signaling pathway. These findings implicate carbohydrates carried by adhesion molecules in modulating NMDA receptor signaling in the brain and demonstrate reversibility of cognitive deficits associated with ablation of a schizophrenia-related adhesion molecule. PMID:20237287

  4. Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase-67 expression and cell proliferation in the adult rat hippocampus.

    Science.gov (United States)

    Kahn, Laëtitia; Alonso, Gérard; Normand, Elisabeth; Manzoni, Olivier J

    2005-01-01

    Altered synaptic transmission and plasticity in brain areas involved in reward and learning are thought to underlie the long-lasting effects of addictive drugs. In support of this idea, opiates reduce neurogenesis [A.J. Eisch et al. (2000) Proceedings of the National Academy of Sciences USA, 97, 7579-7584] and enhance long-term potentiation in adult rodent hippocampus [J.M. Harrison et al. (2002) Journal of Neurophysiology, 87, 2464-2470], a key structure of learning and memory processes. Here we studied how repeated morphine treatment and withdrawal affect cell proliferation and neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus. Our data showed a strong reduction of cellular proliferation in morphine-dependent animals (54% of control) that was followed by a rebound increase after 1 week withdrawal and a return to normal after 2 weeks withdrawal. Morphine dependence was also associated with a drastic reduction in the expression levels of the polysialylated form of neural cell adhesion molecule (68% of control), an adhesion molecule expressed by newly generated neurons and involved in cell migration and structural plasticity. Polysialylated neural cell adhesion molecule levels quickly returned to normal following withdrawal. In morphine-dependent rats, we found a significant increase of glutamate decarboxylase-67 mRNA transcription (170% of control) in dentate gyrus granular cells which was followed by a marked rebound decrease after 1 week withdrawal and a return to normal after 4 weeks withdrawal. Together, the results show, for the first time, that, in addition to reducing cell proliferation and neurogenesis, chronic exposure to morphine dramatically alters neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus.

  5. Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-α.

    Science.gov (United States)

    Chai, Ok Hee; Han, Eui-Hyeog; Lee, Hern-Ku; Song, Chang Ho

    2011-01-31

    Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-α on T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2 cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-Kitw/Kitw-v (W/Wv), congenic normal WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-α directly induce the expression of ICAM-1 and VCAM-1 in W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-α, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-α resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast cells play a key role in a Th2 cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-α.

  6. Interleukin-18-induced cell adhesion molecule expression is associated with feedback regulation by PPAR-γ and NF-κB in Apo E-/- mice.

    Science.gov (United States)

    Bhat, Owais Mohammad; Uday Kumar, P; Harishankar, N; Ravichandaran, L; Bhatia, A; Dhawan, Veena

    2017-02-07

    Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in atherosclerotic lesion formation. Endothelium may regulate leukocyte recruitment by expressing specific adhesion molecules. Interleukin-18 is a proinflammatory cytokine that plays an important role in vascular pathologies. The present study highlights the modulation of adhesion molecules and PPAR-γ by IL-18 and proposes a novel feedback mechanism by which PPAR-γ may regulate IL-18 expression. Three groups of normal chow diet-fed, male Apo E-/- mice, aged 12 weeks (n = 6/group) were employed: Gp I, phosphate-buffered saline (PBS) (2 mo): Gp II, recombinant IL-18 (rIL-18) (1 mo) followed by PBS (1 mo); Gp III, rIL-18 (1 mo) followed by pyrrolidine dithiocarbamate (PDTC) (1 mo). Significantly augmented mRNA expression of ICAM-1 (~5.7-fold), VCAM-1 (~3.6-fold), and NF-κB (~7-fold) was observed in Gp II mice as compared to Gp I, whereas PPAR-γ expression was not altered. PDTC treatment caused a significant downregulation of ICAM-1 (~4.2-fold), VCAM-1(~2-fold), and NF-κB (~4.5-fold) and upregulation of PPAR-γ expression (~5-fold) in Gp III mice. A similar trend was observed in protein expression. In vivo imaging results demonstrated a marked increase in probe (CF750 dye conjugated to VCAM-1 antibody) fluorescence intensity for VCAM-1 expression in Gp II mice, whereas it was moderately decreased in Gp III. PPAR-γ was found to significantly downregulate both IL-18 levels and IL-18-induced adhesion molecules. The underlying mechanism was found to be via inhibition of NF-κB activity by PDTC, thereby leading to decreased adherence of monocytes to the activated endothelial cells and a step to halt the progression and development of atherosclerotic lesions.

  7. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Li L

    2014-02-01

    Full Text Available Lei Li,1,* Dongxi Xiang,2,* Sarah Shigdar,2 Wenrong Yang,3 Qiong Li,2 Jia Lin,4 Kexin Liu,1 Wei Duan2 1College of Pharmacy, Dalian Medical University, Dalian, People's Republic of China; 2School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia; 3School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, VIC, Australia; 4Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, People's Republic of China *These authors contributed equally to this work Abstract: To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles were synthesized and functionalized with ribonucleic acid (RNA Aptamers (Apts against epithelial cell adhesion molecule (EpCAM for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01. Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug

  8. A neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention

    DEFF Research Database (Denmark)

    Secher, Thomas; Novitskaia, V; Berezin, Vladimir

    2006-01-01

    The neural cell adhesion molecule (NCAM) belongs to the immunoglobulin (Ig) superfamily and is composed extracellularly of five Ig-like and two fibronectin type III (F3) modules. It plays a pivotal role in neuronal development and synaptic plasticity. NCAM signals via a direct interaction...... of coordination skills. In adult animals s.c. administration of FGL resulted in a prolonged retention of social memory. We found that FGL rapidly penetrated into the blood and cerebrospinal fluid after both intranasal and s.c. administration and remained detectable in the fluids for up to 5 hours....

  9. A peptide derived from a trans-homophilic binding site in neural cell adhesion molecule induces neurite outgrowth and neuronal survival

    DEFF Research Database (Denmark)

    Køhler, Lene B; Soroka, Vladislav; Korshunova, Irina

    2010-01-01

    The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and synaptic plasticity. The crystal structure of a fragment of NCAM comprising the three N-terminal immunoglobulin (Ig)-like modules indicates that the first and second Ig modules bind to each other...... module. It promoted survival of cultured cerebellar granule neurons (CGNs) and also induced neurite extension in cultures of dopaminergic neurons and CGNs; the latter effect was shown to be dependent on NCAM expression, indicating that plannexin mimics the neuritogenic effect of homophilic NCAM binding....

  10. Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1

    DEFF Research Database (Denmark)

    Bock, E; Richter-Landsberg, C; Faissner, A

    1985-01-01

    -treated rat PC12 pheochromocytoma cells yielded comigrating bands by SDS-PAGE. NILE antibodies reacted with immunopurified L1 antigen, but not with N-CAM and other L2 epitope-bearing glycoproteins from adult mouse brain. Finally, by sequential immunoprecipitation from detergent extracts of [35S......The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule L1 were shown to be immunochemically identical. Immunoprecipitation with L1 and NILE antibodies of [3H]fucose-labeled material from culture supernatants and detergent extracts of NGF...

  11. Effect of gold nanoparticle on stability of the DNA molecule: A study of molecular dynamics simulation.

    Science.gov (United States)

    Izanloo, Cobra

    2017-09-26

    An understanding of the mechanism of DNA interactions with gold nanoparticles is useful in today medicine applications. We have performed a molecular dynamics simulation on a B-DNA duplex (CCTCAGGCCTCC) in the vicinity of a gold nanoparticle with a truncated octahedron structure composed of 201 gold atoms (diameter ∼1.8 nm) to investigate gold nanoparticle (GNP) effects on the stability of DNA. During simulation, the nanoparticle is closed to DNA and phosphate groups direct the particles into the major grooves of the DNA molecule. Because of peeling and untwisting states that are occur at end of DNA, the nucleotide base lies flat on the surface of GNP. The configuration entropy is estimated using the covariance matrix of atom-positional fluctuations for different bases. The results show that when a gold nanoparticle has interaction with DNA, entropy increases. The results of conformational energy and the hydrogen bond numbers for DNA indicated that DNA becomes unstable in the vicinity of a gold nanoparticle. The radial distribution function was calculated for water hydrogen-phosphate oxygen pairs. Almost for all nucleotide, the presence of a nanoparticle around DNA caused water molecules to be released from the DNA duplex and cations were close to the DNA.

  12. Chemical stability of nonwetting, low adhesion self-assembled monolayer films formed by perfluoroalkylsilanization of copper

    Science.gov (United States)

    Hoque, E.; DeRose, J. A.; Hoffmann, P.; Bhushan, B.; Mathieu, H. J.

    2007-03-01

    A self-assembled monolayer (SAM) has been produced by reaction of 1H,1H,2H,2H-perfluorodecyldimethylchlorosilane (PFMS) with an oxidized copper (Cu) substrate and investigated by x-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), friction force microscopy (FFM), a derivative of AFM, and contact angle measurement. FFM showed a significant reduction in the adhesive force and friction coefficient of PFMS modified Cu (PFMS/Cu) compared to unmodified Cu. The perfluoroalkyl SAM on Cu is found to be extremely hydrophobic, yielding sessile drop static contact angles of more than 130° for pure water and a "surface energy" (which is proportional to the Zisman critical surface tension for a Cu surface with 0rms roughness) of 14.5mJ/m2(nM/m). Treatment by exposure to harsh conditions showed that PFMS/Cu SAM can withstand boiling nitric acid (pH=1.8), boiling water, and warm sodium hydroxide (pH =12, 60°C) solutions for at least 30min. Furthermore, no SAM degradation was observed when PFMS/Cu was exposed to warm nitric acid solution for up to 70min at 60°C or 50min at 80°C. Extremely hydrophobic (low surface energy) and stable PFMS/Cu SAMs could be useful as corrosion inhibitors in micro/nanoelectronic devices and/or as promoters for antiwetting, low adhesion surfaces or dropwise condensation on heat exchange surfaces.

  13. Effect of autoclave induced low-temperature degradation on the adhesion energy between yttria-stabilized zirconia veneered with porcelain.

    Science.gov (United States)

    Li, Kai Chun; Waddell, J Neil; Prior, David J; Ting, Stephanie; Girvan, Liz; van Vuuren, Ludwig Jansen; Swain, Michael V

    2013-11-01

    To investigate the effect of autoclave induced low-temperature degradation on the adhesion energy between yttria-stabilized zirconia veneered with porcelain. The strain energy release rate using a four-point bending stable fracture test was evaluated for two different porcelains [leucite containing (VM9) and glass (Zirox) porcelain] veneered to zirconia. Prior to veneering the zirconia had been subjected to 0 (control), 1, 5, 10 and 20 autoclave cycles. The specimens were manufactured to a total bi-layer dimension of 30 mm × 8 mm × 3 mm. Subsequent scanning electron microscopy/energy dispersive spectrometry, electron backscatter diffraction and X-ray diffraction analysis were performed to identify the phase transformation and fracture behavior. The strain energy release rate for debonding of the VM9 specimens were significantly higher (pautoclave cycles lowered the strain energy release rate significantly (pautoclave cycles between 5 and 20. The monoclinic phase reverted back to tetragonal phase after undergoing conventional porcelain firing cycles. EBSD data showed significant changes of the grain size distribution between the control and autoclaved specimen (cycle 20). Increasing autoclave cycles only significantly decreased the adhesion of the VM9 layered specimens. In addition, a conventional porcelain firing schedule completely reverted the monoclinic phase back to tetragonal. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  14. Change in organic molecule adhesion on α-alumina (Sapphire) with change in NaCl and CaCl2 solution salinity

    DEFF Research Database (Denmark)

    Juhl, Klaus; Bovet, Nicolas Emile; Hassenkam, Tue

    2014-01-01

    that the tips adhere to alumina through hydrogen bonding when only water is present. In solutions containing NaCl and CaCl2, cations are adsorbed but Cl- is not. When NaCl solutions are replaced by CaCl2, Ca2+ replaces Na+, but rinsing with ultrapure deionized water (pH 5.6) could not restore the original......We investigated the adhesion of two functional groups to α-alumina as a model for the adsorption of organic molecules on clay minerals. Interactions between organic compounds and clay minerals play an important role in processes such as drinking water treatment, remediation of contaminated soil......, oil recovery, and fabricating complicated nanomaterials, and there have been claims that organic compound-clay mineral interaction created the ordering that is necessary for the genesis of life. In many organisms, interaction between organic molecules and biominerals makes it possible to control...

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

    DEFF Research Database (Denmark)

    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...... 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......) and interstitial collagenase (matrix metalloproteinase 1), indicating that cellular expression of the recognition molecule NCAM regulates the metabolism of the surrounding matrix....

  16. Aspirin and pravastatin reduce lectin-like oxidized low density lipoprotein receptor-1 expression, adhesion molecules and oxidative stress in human coronary artery endothelial cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Jia-wei; ZHOU Shi-bei; TAN Zhi-ming

    2010-01-01

    Background Oxidative stress and inflammation are important steps in the pathogenesis of atherosclerosis. We postulated that therapeutic concentrations of aspirin and pravastatin, especially in combination, may suppress oxidative stress and inflammation in endothelial cells, and this concept was examined in human coronary artery endothelial cells (HCAECs).Methods Human coronary artery endothelial cells were cultured and treated with oxidized-low density iipoprotein (ox-LDL, 60 μg/ml for 24 hours) alone, or pre-treated with aspirin (1, 2 or 5 mmol/L), pravastatin (1, 5 or 10 μmol/L) or their combination (1 mmol/L aspirin and 5 μmol/L pravastatin), followed by ox-LDL treatment. After respective treatment,superoxide anion production, p38 mitogen activated protein kinase and transcription factor NF-κB activation, protein expression of lectin-like ox-LDL receptor-1 (LOX-1) and adhesion molecules, and monocyte adhesion were measured.Results Ox-LDL treatment greatly elicited its receptor LOX-1 expression, superoxide anion production and inflammatory response, which were minimally affected by low concentration of aspidn (1 mmol/L) or pravastatin (5 μmol/L), but were markedly decreased by their combination. Activation of p38 mitogen activated protein kinase and NF-κB, the expression of intercellular adhesion molecule-1 and monocyte chemotactic protein-1, which were only mildly affected by aspirin or pravastatin alone, were significantly attenuated by their combination. As a consequence, monocyte adhesion to endothelial cells was markedly attenuated by the combination of the two agents. Well-known anti-oxidants α-tocopherol and γ-tocopherol had similar inhibitory effects on ox-LDL-mediated oxidative stress and LOX-1 expression as well as monocyte adhesion as did the combination of aspirin and pravastatin.Conclusions These studies point to a positive interaction between aspidn and pravastatin with regard to endothelial biology. Anti-oxidant and subsequent anti

  17. FRET based quantification and screening technology platform for the interactions of leukocyte function-associated antigen-1 (LFA-1 with intercellular adhesion molecule-1 (ICAM-1.

    Directory of Open Access Journals (Sweden)

    Sandeep Chakraborty

    Full Text Available The interaction between leukocyte function-associated antigen-1(LFA-1 and intercellular adhesion molecule-1 (ICAM-1 plays a pivotal role in cellular adhesion including the extravasation and inflammatory response of leukocytes, and also in the formation of immunological synapse. However, irregular expressions of LFA-1 or ICAM-1 or both may lead to autoimmune diseases, metastasis cancer, etc. Thus, the LFA-1/ICAM-1 interaction may serve as a potential therapeutic target for the treatment of these diseases. Here, we developed one simple 'in solution' steady state fluorescence resonance energy transfer (FRET technique to obtain the dissociation constant (Kd of the interaction between LFA-1 and ICAM-1. Moreover, we developed the assay into a screening platform to identify peptides and small molecules that inhibit the LFA-1/ICAM-1 interaction. For the FRET pair, we used Alexa Fluor 488-LFA-1 conjugate as donor and Alexa Fluor 555-human recombinant ICAM-1 (D1-D2-Fc as acceptor. From our quantitative FRET analysis, the Kd between LFA-1 and D1-D2-Fc was determined to be 17.93±1.34 nM. Both the Kd determination and screening assay were performed in a 96-well plate platform, providing the opportunity to develop it into a high-throughput assay. This is the first reported work which applies FRET based technique to determine Kd as well as classifying inhibitors of the LFA-1/ICAM-1 interaction.

  18. Cannabinoids modulate Olig2 and polysialylated neural cell adhesion molecule expression in the subventricular zone of post-natal rats through cannabinoid receptor 1 and cannabinoid receptor 2.

    Science.gov (United States)

    Arévalo-Martín, Angel; García-Ovejero, Daniel; Rubio-Araiz, Ana; Gómez, Oscar; Molina-Holgado, Francisco; Molina-Holgado, Eduardo

    2007-09-01

    The subventricular zone (SVZ) is a source of post-natal glial precursors that can migrate to the overlying white matter, where they may differentiate into oligodendrocytes. We showed that, in the post-natal SVZ ependymocytes, radial glia and astrocyte-like cells express cannabinoid receptor 1 (CB1), whereas cannabinoid receptor 2 (CB2) is found in cells expressing the polysialylated neural cell adhesion molecule. To study CB1 and CB2 function, post-natal rats were exposed to selective CB1 or CB2 agonists (arachidonyl-2-chloroethylamide and JWH-056, respectively) for 15 days. Accordingly, we found that CB1 activation increases the number of Olig2-positive cells in the dorsolateral SVZ, whereas CB2 activation increases polysialylated neural cell adhesion molecule expression in this region. As intense myelination occurs during the first weeks of post-natal development, we examined how modulating these factors affected the expression of myelin basic protein. Pharmacological administration of agonists and antagonists of CB1 and CB2 showed that the activation of both receptors is needed to augment the expression of myelin basic protein in the subcortical white matter.

  19. Effect of propionylcarnitine on changes in endothelial function and plasma levels of adhesion molecules induced by acute exercise in patients with intermittent claudication.

    Science.gov (United States)

    Silvestro, Antonio; Schiano, Vittorio; Bucur, Roxana; Brevetti, Gregorio; Scopacasa, Francesco; Chiariello, Massimo

    2006-01-01

    In patients with intermittent claudication, treadmill exercise may cause acute deterioration of endothelial function and increase in plasma concentrations of adhesion molecules. The authors evaluated the efficacy of intravenously administered propionylcarnitine (PLC)in preventing these phenomena. Thirty-six claudicants with postexercise decrease in brachial artery flow-mediated dilation (FMD)were randomized to either placebo or PLC (600 mg as a single bolus followed by 1 mg/kg/min for 60 minutes).In the 18 patients randomized to placebo, FMD markedly decreased with exercise before (from 6.8 +/-0.4% to 4.0 +/-0.4%; p or=45% (ie, the median FMD reduction in the entire group of 36 patients), and found that the exercise-induced FMD decrease was less after PLC than after placebo (p = 0.046, ANOVA). In the same subgroup, the exercise-induced increase in plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) was significantly higher before than after treatment in patients randomized to PLC (23.4 +/-5% vs 15.3 +/-7%, p = 0.007). In conclusion, in patients with intermittent claudication suffering from a greater endothelial derangement after treadmill, PLC administration provided a protective effect against deterioration of FMD and increase of sVCAM-1 induced by exercise.

  20. A protease storm cleaves a cell-cell adhesion molecule in cancer: multiple proteases converge to regulate PTPmu in glioma cells.

    Science.gov (United States)

    Phillips-Mason, Polly J; Craig, Sonya E L; Brady-Kalnay, Susann M

    2014-09-01

    Cleavage of the cell-cell adhesion molecule, PTPµ, occurs in human glioblastoma multiforme brain tumor tissue and glioma cell lines. PTPµ cleavage is linked to increased cell motility and growth factor independent survival of glioma cells in vitro. Previously, PTPµ was shown to be cleaved by furin in the endoplasmic reticulum to generate membrane associated E- (extracellular) and P- (phosphatase) subunits, and by ADAMs and the gamma secretase complex at the plasma membrane. We also identified the presence of additional extracellular and intracellular PTPµ fragments in brain tumors. We set out to biochemically analyze PTPµ cleavage in cancer cells. We determined that, in addition to the furin-processed form of PTPµ, a pool of 200 kDa full-length PTPµ exists at the plasma membrane that is cleaved directly by ADAM to generate a larger shed form of the PTPµ extracellular segment. Notably, in glioma cells, full-length PTPµ is also subject to calpain cleavage, which generates novel PTPµ fragments not found in other immortalized cells. We also observed glycosylation and phosphorylation differences in the cancer cells. Our data suggest that an additional serine protease also contributes to PTPµ shedding in glioma cells. We hypothesize that a "protease storm" occurs in cancer cells whereby multiple proteases converge to reduce the presence of cell-cell adhesion molecules at the plasma membrane and to generate protein fragments with unique biological functions. As a consequence, the "protease storm" could promote the migration and invasion of tumor cells.

  1. The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

    Directory of Open Access Journals (Sweden)

    Carlos A. Díaz-Balzac

    2015-06-01

    Full Text Available Neurite branching is essential for correct assembly of neural circuits, yet it remains a poorly understood process. For example, the neural cell adhesion molecule KAL-1/anosmin-1, which is mutated in Kallmann syndrome, regulates neurite branching through mechanisms largely unknown. Here, we show that KAL-1/anosmin-1 mediates neurite branching as an autocrine co-factor with EGL-17/FGF through a receptor complex consisting of the conserved cell adhesion molecule SAX-7/L1CAM and the fibroblast growth factor receptor EGL-15/FGFR. This protein complex, which appears conserved in humans, requires the immunoglobulin (Ig domains of SAX-7/L1CAM and the FN(III domains of KAL-1/anosmin-1 for formation in vitro as well as function in vivo. The kinase domain of the EGL-15/FGFR is required for branching, and genetic evidence suggests that ras-mediated signaling downstream of EGL-15/FGFR is necessary to effect branching. Our studies establish a molecular pathway that regulates neurite branching during development of the nervous system.

  2. Focal nodular hyperplasia of the liver: composition of the extracellular matrix and expression of cell-cell and cell-matrix adhesion molecules.

    Science.gov (United States)

    Scoazec, J Y; Flejou, J F; D'Errico, A; Couvelard, A; Kozyraki, R; Fiorentino, M; Grigioni, W F; Feldmann, G

    1995-10-01

    We studied by immunohistochemistry 25 cases of focal nodular hyperplasia (FNH) to evaluate the composition of the extracellular matrix and the expression and distribution of endothelial cell-cell adhesion molecules and integrin receptors. The extracellular matrix of FNH retained the overall organization of that of normal liver. The matr