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Sample records for adhesion molecule ncam

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

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Walmod, Peter

    2008-01-01

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

  2. 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...

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

    DEFF Research Database (Denmark)

    Gaardsvoll, H; Krog, L; Zhernosekov, D

    1993-01-01

    The neural cell adhesion molecule (NCAM) has been implicated in cellular interactions involved in cardiac morphogenesis and innervation. In this study, expression of NCAM mRNA and protein was characterized in rat heart during postnatal development and aging (postnatal days 1, 10, 40, 270, and 730...

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

    DEFF Research Database (Denmark)

    Jørgensen, Ole Steen

    1988-01-01

    The size of the soluble form of the human cerebrospinal fluid (CSF) neural cell adhesion molecule, NCAM-sol, was by gel permeation chromatography estimated to 160-250 kDa. Within the CSF the concentration of NCAM-sol was found about 15-25% increased in lumbar fluid and 25% increased in ventricular...... fluid, both compared to cisternal fluid. Whereas prealbumin was found evenly distributed in CSF, albumin was relatively enriched in lumbar fluid. The concentrations of NCAM-sol and prealbumin were measured in lumbar CSF from psychiatric patients. Prealbumin was increased 7.2% and NCAM-sol was decreased...

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

    DEFF Research Database (Denmark)

    Zecchini, Silvia; Bombardelli, Lorenzo; Decio, Alessandra

    2011-01-01

    glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM......Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface...... stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting...

  6. 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......) and interstitial collagenase (matrix metalloproteinase 1), indicating that cellular expression of the recognition molecule NCAM regulates the metabolism of the surrounding matrix....

  7. Pharmacological approach for targeting dysfunctional brain plasticity: Focus on neural cell adhesion molecule (NCAM).

    Science.gov (United States)

    Aonurm-Helm, Anu; Jaako, Külli; Jürgenson, Monika; Zharkovsky, Alexander

    2016-11-01

    Brain plasticity refers to the ability of the brain to undergo functionally relevant adaptations in response to external and internal stimuli. Alterations in brain plasticity have been associated with several neuropsychiatric disorders, and current theories suggest that dysfunctions in neuronal circuits and synaptogenesis have a major impact in the development of these diseases. Among the molecules that regulate brain plasticity, neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM have been of particular interest for years because alterations in NCAM and PSA-NCAM levels have been associated with memory impairment, depression, autistic spectrum disorders and schizophrenia. In this review, we discuss the roles of NCAM and PSA-NCAM in the regulation of brain plasticity and, in particular, their roles in the mechanisms of depression. We also demonstrate that the NCAM-mimetic peptides FGL and Enreptin are able to restore disrupted neuronal plasticity. FGL peptide has also been demonstrated to ameliorate the symptoms of depressive-like behavior in NCAM-deficient mice and therefore, may be considered a new drug candidate for the treatment of depression as well as other neuropsychiatric disorders with disrupted neuroplasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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...

  9. Crystal structure of the Ig1 domain of the neural cell adhesion molecule NCAM2 displays domain swapping

    DEFF Research Database (Denmark)

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

    2008-01-01

    The crystal structure of the first immunoglobulin (Ig1) domain of neural cell adhesion molecule 2 (NCAM2/OCAM/RNCAM) is presented at a resolution of 2.7 A. NCAM2 is a member of the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). In the structure, two Ig domains interact by domain...

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

    DEFF Research Database (Denmark)

    Jørgensen, Ole Steen

    1988-01-01

    The size of the soluble form of the human cerebrospinal fluid (CSF) neural cell adhesion molecule, NCAM-sol, was by gel permeation chromatography estimated to 160-250 kDa. Within the CSF the concentration of NCAM-sol was found about 15-25% increased in lumbar fluid and 25% increased in ventricula...... 15.1% in depressed patients. The changes were partially normalized during recovery from the depression. The findings can be explained by hypothesizing that endogenous depression is associated with an increased choroid plexus activity and CSF production....

  11. Differential expression of the neural cell adhesion molecule NCAM 140 in human pituitary tumors

    OpenAIRE

    Aletsee-Ufrecht, M. C.; Langley, O. K.; Gratzl, O.; Gratzl, Manfred

    1990-01-01

    We have analyzed the expression of the intracellular marker protein neuron specific enolase (NSE), synaptophysin (SYN) and of the cell surface marker NCAM (neural cell adhesion molecule) in both normal human hypophysis and in pituitary adenomas in order to explore their potential use as diagnostic tools. All adenomas (4 prolactinomas, 3 growth hormone (GH) producing adenomas and 4 inactive adenomas) showed SYN and NSE immunoreactivity on tissue sections and this was confirmed by immunoblots. ...

  12. 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......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...... extracellular guidance cues to intracellular events and thereby regulating neurite outgrowth. In this review, we focus on two CAMs, the neural cell adhesion molecule (NCAM) and N-cadherin, and their ability to mediate signaling associated with a neurite outgrowth response. In particular, we will focus on direct...

  13. Insulin and IGF1 modulate turnover of polysialylated neural cell adhesion molecule (PSA-NCAM) in a process involving specific extracellular matrix components.

    Science.gov (United States)

    Monzo, Hector J; Park, Thomas I H; Dieriks, Birger V; Jansson, Deidre; Faull, Richard L M; Dragunow, Mike; Curtis, Maurice A

    2013-09-01

    Cellular interactions mediated by the neural cell adhesion molecule (NCAM) are critical in cell migration, differentiation and plasticity. Switching of the NCAM-interaction mode, from adhesion to signalling, is determined by NCAM carrying a particular post-translational modification, polysialic acid (PSA). Regulation of cell-surface PSA-NCAM is traditionally viewed as a direct consequence of polysialyltransferase activity. Taking advantage of the polysialyltransferase Ca²⁺-dependent activity, we demonstrate in TE671 cells that downregulation of PSA-NCAM synthesis constitutes a necessary but not sufficient condition to reduce cell-surface PSA-NCAM; instead, PSA-NCAM turnover required internalization of the molecule into the cytosol. PSA-NCAM internalization was specifically triggered by collagen in the extracellular matrix (ECM) and prevented by insulin-like growth factor (IGF1) and insulin. Our results pose a novel role for IGF1 and insulin in controlling cell migration through modulation of PSA-NCAM turnover at the cell surface. Neural cell adhesion molecules (NCAMs) are critically involved in cell differentiation and migration. Polysialylation (PSA)/desialylation of NCAMs switches their functional interaction mode and, in turn, migration and differentiation. We have found that the desialylation process of PSA-NCAM occurs via endocytosis, induced by collagen-IV and blocked by insulin-like growth factor (IGF1) and insulin, suggesting a novel association between PSA-NCAM, IGF1/insulin and brain/tumour plasticity. © 2013 International Society for Neurochemistry.

  14. 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...... of the immunoglobulin (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM homophilic adhesion. The present study addressed the biological significance of the so called dense zipper formation of NCAM. Two peptides, termed dennexinA and dennexinB, were modeled after the contact interfaces...... 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...

  15. 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

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

  16. 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...

  17. Expression, crystallization and preliminary X-ray analysis of extracellular modules of the neural cell-adhesion molecules NCAM and L1

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Kasper, Christina; Gajhede, Michael

    2004-01-01

    Recombinant proteins consisting of either the four or five amino-terminal immunoglobulin (Ig) modules of the rat neural cell-adhesion molecule NCAM or the whole extracellular part [six Ig and five fibronectin type III (F3) modules] of mouse L1 have been expressed in Drosophila S2 cells. The prote......Recombinant proteins consisting of either the four or five amino-terminal immunoglobulin (Ig) modules of the rat neural cell-adhesion molecule NCAM or the whole extracellular part [six Ig and five fibronectin type III (F3) modules] of mouse L1 have been expressed in Drosophila S2 cells...

  18. Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF

    DEFF Research Database (Denmark)

    Nielsen, Janne; Gotfryd, Kamil; Li, Shizhong

    2009-01-01

    The formation of appropriate neuronal circuits is an essential part of nervous system development and relies heavily on the outgrowth of axons and dendrites and their guidance to their respective targets. This process is governed by a large array of molecules, including glial cell line......-derived neurotrophic factor (GDNF) and the neural cell adhesion molecule (NCAM), the interaction of which induce neurite outgrowth. In the present study the requirements for NCAM-mediated GDNF-induced neurite outgrowth were investigated in cultures of hippocampal neurons, which do not express Ret. We demonstrate...

  19. 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

    , before the patients received chemotherapy. The polyclonal antibody used in the assay recognized all three isoforms of NCAM. The concentration of NCAM was related to clinical parameters of the patients such as age, sex, blood group status, stage of disease, organ site involvement of metastases, survival...

  20. Structural basis of cell-cell adhesion by NCAM

    DEFF Research Database (Denmark)

    Kasper, C; Rasmussen, H; Kastrup, Jette Sandholm Jensen

    2000-01-01

    The neural cell adhesion molecule NCAM, a member of the immunoglobulin superfamily, mediates cell-cell recognition and adhesion via a homophilic interaction. NCAM plays a key role during development and regeneration of the nervous system and is involved in synaptic plasticity associated with memory...... and learning. The 1.85 A crystal structure of the two N-terminal extracellular domains of NCAM reported here provides a structural basis for the homophilic interaction. The molecular packing of the two-domain structure reveals a cross shaped antiparallel dimer, and provides fundamental insight into trans-cellular...

  1. Polysialylated-neural cell adhesion molecule (PSA-NCAM in the human trigeminal ganglion and brainstem at prenatal and adult ages

    Directory of Open Access Journals (Sweden)

    Melis Tiziana

    2008-11-01

    Full Text Available Abstract Background The polysialylated neuronal cell adhesion molecule (PSA-NCAM is considered a marker of developing and migrating neurons and of synaptogenesis in the immature vertebrate nervous system. However, it persists in the mature normal brain in some regions which retain a capability for morphofunctional reorganization throughout life. With the aim of providing information relevant to the potential for dynamic changes of specific neuronal populations in man, this study analyses the immunohistochemical occurrence of PSA-NCAM in the human trigeminal ganglion (TG and brainstem neuronal populations at prenatal and adult age. Results Western blot analysis in human and rat hippocampus supports the specificity of the anti-PSA-NCAM antibody and the immunodetectability of the molecule in postmortem tissue. Immunohistochemical staining for PSA-NCAM occurs in TG and several brainstem regions during prenatal life and in adulthood. As a general rule, it appears as a surface staining suggestive of membrane labelling on neuronal perikarya and proximal processes, and as filamentous and dot-like elements in the neuropil. In the TG, PSA-NCAM is localized to neuronal perikarya, nerve fibres, pericellular networks, and satellite and Schwann cells; further, cytoplasmic perikaryal staining and positive pericellular fibre networks are detectable with higher frequency in adult than in newborn tissue. In the adult tissue, positive neurons are mostly small- and medium-sized, and amount to about 6% of the total ganglionic population. In the brainstem, PSA-NCAM is mainly distributed at the level of the medulla oblongata and pons and appears scarce in the mesencephalon. Immunoreactivity also occurs in discretely localized glial structures. At all ages examined, PSA-NCAM occurs in the spinal trigeminal nucleus, solitary nuclear complex, vestibular and cochlear nuclei, reticular formation nuclei, and most of the precerebellar nuclei. In specimens of different age

  2. Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM)

    Science.gov (United States)

    Euteneuer, Sara; Yang, Kuo H.; Chavez, Eduardo; Leichtle, Anke; Loers, Gabriele; Olshansky, Adel; Pak, Kwang; Schachner, Melitta; Ryan, Allen F.

    2013-01-01

    Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of spiral ganglion neurons (SGNs), the primary neurons of the auditory system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor α1 (GFRα1) via recruitment of transmembrane receptors: Ret (re-arranged during transformation) and/or NCAM (neural cell adhesion molecule). Here we show that GDNF enhances neuritogenesis in organotypic cultures of spiral ganglia from 5-day-old rats and mice. Addition of GFRα1-Fc increases this effect. GDNF/GFRα1-Fc stimulation activates intracellular PI3K/Akt and MEK/Erk signaling cascades as detected by Western blot analysis of cultures prepared from rats at postnatal days 5 (P5, before the onset of hearing) and 20 (P20, after the onset of hearing). Both cascades mediate GDNF stimulation of neuritogenesis, since application of the Akt inhibitor Wortmannin or the Erk inhibitor U0126 abolished GDNF/GFRα1-Fc stimulated neuritogenesis in P5 rats. Since cultures of P5 NCAM-deficient mice failed to respond by neuritogenesis to GDNF/GFRα1-Fc, we conclude that NCAM serves as a receptor for GDNF signaling responsible for neuritogenesis in early postnatal spiral ganglion. PMID:23262364

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

    DEFF Research Database (Denmark)

    Aonurm-Helm, Anu; Jurgenson, Monika; Zharkovsky, Tamara

    2008-01-01

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

  4. 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...... with the Src-family kinases, were also involved in neuritogenesis induced by physiological, homophilic NCAM interactions. Thus, unanticipated mechanisms of Ca2+ homeostasis are shown to be activated by NCAM and to contribute to neuronal differentiation....

  5. Molecular mechanisms of NCAM function

    DEFF Research Database (Denmark)

    Hinsby, Anders M; Berezin, Vladimir; Bock, Elisabeth

    2004-01-01

    Neural cell adhesion molecule (NCAM) was originally characterised as a homophilic cell adhesion molecule (CAM) abundantly expressed in the nervous system. However, the last decade of research has challenged the traditional view and defined novel roles for NCAM. NCAM is now considered a signaling ...

  6. 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...

  7. 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...

  8. NCAM regulates cell motility

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  9. Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression

    Directory of Open Access Journals (Sweden)

    Sakashita Hideaki

    2008-12-01

    Full Text Available Abstract Background Cimetidine, a histamine type-2 receptor antagonist, has been reported to inhibit the growth of glandular tumors such as colorectal cancer, however the mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma is well known as a malignant salivary gland tumor which preferentially invades neural tissues. We demonstrated previously that human salivary gland tumor (HSG cells spontaneously express neural cell adhesion molecule (NCAM, that HSG cell proliferation may be controlled via a homophilic (NCAM-NCAM binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. We further demonstrated that cimetidine inhibited NCAM expression and induced apoptosis in HSG cells. Here, we investigated the effects of cimetidine on growth and perineural/neural invasion of salivary gland tumor cells. Methods In this study, we have examined the effect of cimetidine on cancer cell adhesion to neural cells in vitro, one of the critical steps of cancer invasion and metastasis. We have also used an in vivo carcinogenesis model to confirm the effect of cimetidine. Results We have demonstrated for the first time that cimetidine can block the adhesion of HSG cells to neural cell monolayers and that it can also induce significant apoptosis in the tumor mass in a nude mouse model. We also demonstrated that these apoptotic effects of cimetidine might occur through down-regulation of the cell surface expression of NCAM on HSG cells. Cimetidine-mediated down-regulation of NCAM involved suppression of the nuclear translocation of NF-κB, a transcriptional activator of NCAM gene expression. Conclusion These findings suggest that growth and perineural/neural invasion of salivary gland tumors can be blocked by administration of cimetidine via induction of apoptosis and in which NCAM plays a role.

  10. 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...

  11. Adhesion molecules

    CERN Document Server

    Preedy, Victor R

    2016-01-01

    This book covers the structure and classification of adhesion molecules in relation to signaling pathways and gene expression. It discusses immunohistochemical localization, neutrophil migration, and junctional, functional, and inflammatory adhesion molecules in pathologies such as leukocyte decompression sickness and ischemia reperfusion injury. Highlighting the medical applications of current research, chapters cover diabetes, obesity, and metabolic syndrome; hypoxia; kidney disease; smoking, atrial fibrillation, and heart disease, the brain and dementia; and tumor proliferation. Finally, it looks at molecular imaging and bioinformatics, high-throughput technologies, and chemotherapy.

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

    DEFF Research Database (Denmark)

    Christensen, Claus; Berezin, Vladimir; Bock, Elisabeth

    2011-01-01

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

  13. 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...

  14. 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

    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......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...

  15. Effect of human colorectal carcinogenesis on the neural cell adhesion molecule expression and polysialylation.

    Science.gov (United States)

    Fernández-Briera, A; García-Parceiro, I; Cuevas, E; Gil-Martín, E

    2010-01-01

    Although downregulation of neural cell adhesion molecule (NCAM) has been correlated with poor prognosis in colorectal cancer (CRC), it is also possible that colon cancer spreading comes from reducing tumor cell adhesion through NCAM polysialylation, as occurs in lung carcinoma or Wilms' tumor. To prove this hypothesis, we have performed a prospective study on tumor and control specimens from 39 CRC patients, which were immunostained for NCAM and PSA (polysialic acid) expression. Tumor versus control expression of NCAM and PSA epitopes in tissue specimens, as well as correlation between tumor expression and clinicopathological features, were statistically analyzed. Results showed a low constitutive expression of NCAM and PSA (PSA-NCAM) in control tissue, which reached a statistically significant increase in the tumor tissue. Likewise, the presence and number of lymph node metastases at surgery were correlated with NCAM expression and PSA/NCAM coexpression. These data highlight the importance of taking into account PSA-associated epitopes when dealing with NCAM cell expression studies in tumor development and progression. The analysis of PSA and NCAM expression in CRC suggests a new way, other than downregulation of NCAM, in order to escape contact inhibition and promote cell tumor spreading in colorectal cancer. Copyright 2010 S. Karger AG, Basel.

  16. Polysialic Acid/Neural Cell Adhesion Molecule Modulates the Formation of Ductular Reactions in Liver Injury

    OpenAIRE

    Tsuchiya, Atsunori; Lu, Wei-Yu; Weinhold, Birgit; Boulter, Luke; Stutchfield, Benjamin M.; Williams, Michael J.; Guest, Rachel V.; Minnis-Lyons, Sarah E.; MacKinnon, Alison C.; Schwarzer, David; Ichida, Takafumi; Nomoto, Minoru; Aoyagi, Yutaka; Gerardy-Schahn, Rita; Forbes, Stuart J.

    2014-01-01

    In severe liver injury, ductular reactions (DRs) containing bipotential hepatic progenitor cells (HPCs) branch from the portal tract. Neural cell adhesion molecule (NCAM) marks bile ducts and DRs, but not mature hepatocytes. NCAM mediates interactions between cells and surrounding matrix; however, its role in liver development and regeneration is undefined. Polysialic acid (polySia), a unique posttranslational modifier of NCAM, is produced by the enzymes, ST8SiaII and ST8SiaIV, and weakens NC...

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

    DEFF Research Database (Denmark)

    Edvardsen, K; Bock, E; Jirus, S

    1997-01-01

    A cDNA encoding the human transmembrane 140 kDa isoform of the neural cell adhesion molecule (NCAM) was transfected into the highly invasive MDA-MB-231 human breast cancer cell line. Transfectants with a homogeneous expression of NCAM showed a restricted capacity for penetration of an artificial...... basement membrane. However, when injected into nude mice, both control and NCAM-expressing cell lines produced equally invasive tumors. Tumors generated from NCAM-transfected cells were heterogeneous, containing NCAM-positive as well as NCAM-negative areas, indicating the existence of host factors capable...... of modulating NCAM expression in vivo. In nude mice, NCAM-transfected cells developed tumors with longer latency periods and slower growth rates than tumors induced by NCAM-negative control cells, implying that NCAM may be involved not only in adhesive and motile behavior of tumor cells but also in their growth...

  18. 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...

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

    DEFF Research Database (Denmark)

    Nybroe, O; Albrechtsen, M; Dahlin, J

    1985-01-01

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

  20. NCAM regulates cell motility

    DEFF Research Database (Denmark)

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

    2002-01-01

    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells independe...

  1. ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation

    DEFF Research Database (Denmark)

    Hinsby, Anders M; Lundfald, Line; Ditlevsen, Dorte K

    2004-01-01

    Homophilic binding in trans of the neural cell adhesion molecule (NCAM) mediates adhesion between cells and leads, via activation of intracellular signaling cascades, to neurite outgrowth in primary neurons as well as in the neuronal cell line PC12. NCAM mediates neurite extension in PC12 cells....... Here, we investigated the involvement of adaptor proteins in NCAM and fibroblast growth factor 2 (FGF2)-mediated neurite outgrowth in the PC12-E2 cell line. We found that both FGFR substrate-2 and Grb2 play important roles in NCAM as well as in FGF2-stimulated events. In contrast, the docking protein...... ShcA was pivotal to neurite outgrowth induced by NCAM, but not by FGF2, in PC12 cells. Moreover, in rat cerebellar granule neurons, phosphorylation of ShcA was stimulated by an NCAM mimicking peptide, but not by FGF2. This activation was blocked by inhibitors of both FGFR and Fyn, indicating that NCAM...

  2. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

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

    DEFF Research Database (Denmark)

    Edvardsen, K; Bock, E; Jirus, S

    1997-01-01

    A cDNA encoding the human transmembrane 140 kDa isoform of the neural cell adhesion molecule (NCAM) was transfected into the highly invasive MDA-MB-231 human breast cancer cell line. Transfectants with a homogeneous expression of NCAM showed a restricted capacity for penetration of an artificial...... basement membrane. However, when injected into nude mice, both control and NCAM-expressing cell lines produced equally invasive tumors. Tumors generated from NCAM-transfected cells were heterogeneous, containing NCAM-positive as well as NCAM-negative areas, indicating the existence of host factors capable...

  4. 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…

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

    DEFF Research Database (Denmark)

    Andersson, A M; Gaardsvoll, H; Giladi, E

    1990-01-01

    A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... the five NCAM mRNAs in rat brain....

  6. 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

  7. Insight into the structural mechanism of the bi-modal action of an NCAM mimetic, the C3 peptide

    DEFF Research Database (Denmark)

    Kiselyov, Vladislav V; Li, Shizhong; Berezin, Vladimir

    2009-01-01

    C3, a synthetic peptide binding to the Ig1 module of the neural cell adhesion molecule (NCAM) has previously been identified and shown to inhibit NCAM homophilic binding and NCAM-mediated activation of the fibroblast growth factor (FGF) receptor (FGFR). However, C3 can also stimulate signalling...

  8. Cell Adhesion Molecules of the Immunoglobulin Superfamily in the Nervous System

    DEFF Research Database (Denmark)

    Walmod, Peter Schledermann; Pedersen, Martin Volmer; Berezin, Vladimir

    2007-01-01

    CAMs belonging to IgSF, that exclusively or in part, are expressed in the nervous system. The chapter includes descriptions of myelin protein zero (P0), integrin-associated protein (CD47), neuroplastin, activated leukocyte-cell adhesion molecule (ALCAM), melanoma cell adhesion molecule (MCAM......Cell adhesion molecules (CAMs) are proteins mediating cell-cell or cell-extracellular matrix (ECM) interactions. CAMs are traditionally divided into four groups, the cadherins, the selectins, the integrins and CAMs belonging to the immunoglobulin superfamily (IgSF). The present chapter describes......), myelinassociated glycoprotein (MAG), the neural cell adhesion molecules 1 and 2 (NCAM, NCAM2), Down Syndrome cell adhesion molecule (DSCAM) and Down Syndrome cell adhesion molecule-like-1 (DSCAML1), sidekick 1 and 2 (SDK1, SDK2), signal-regulatory proteins (SIRPs), nectins, nectin-like proteins (necls...

  9. Insulin promotes cell migration by regulating PSA-NCAM

    International Nuclear Information System (INIS)

    Monzo, Hector J.; Coppieters, Natacha; Park, Thomas I.H.; Dieriks, Birger V.; Faull, Richard L.M.; Dragunow, Mike; Curtis, Maurice A.

    2017-01-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. - Highlights: • Insulin modulates PSA-NCAM turnover through upregulation of p-FAK. • P-FAK modulates αv-integrin/PSA-NCAM clustering. • αv-integrin acts as a carrier for PSA-NCAM endocytosis. • Cell migration is promoted by cell surface PSA. • Insulin promotes PSA-dependent migration in vitro.

  10. Insulin promotes cell migration by regulating PSA-NCAM

    Energy Technology Data Exchange (ETDEWEB)

    Monzo, Hector J.; Coppieters, Natacha [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Park, Thomas I.H. [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Dieriks, Birger V.; Faull, Richard L.M. [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Dragunow, Mike [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Curtis, Maurice A., E-mail: m.curtis@auckland.ac.nz [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand)

    2017-06-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. - Highlights: • Insulin modulates PSA-NCAM turnover through upregulation of p-FAK. • P-FAK modulates αv-integrin/PSA-NCAM clustering. • αv-integrin acts as a carrier for PSA-NCAM endocytosis. • Cell migration is promoted by cell surface PSA. • Insulin promotes PSA-dependent migration in vitro.

  11. 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...... 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...

  12. 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...

  13. Neural cell adhesion molecules in rodent brains isolated by monoclonal antibodies with cross-species reactivity.

    OpenAIRE

    Chuong, C M; McClain, D A; Streit, P; Edelman, G M

    1982-01-01

    Previous studies in this laboratory have led to the identification and purification of a chicken cell surface protein named "neural cell adhesion molecule" (N-CAM) that is involved in neural cell-cell and neurite-neurite interactions. In the present investigation, we have found that a similar molecule exists in the mouse and have confirmed that it is also present in rat neural tissue. A monoclonal antibody to chicken N-CAM that crossreacted with mouse and rat brains and an independently deriv...

  14. Expression of neural cell adhesion molecule in human liver development and in congenital and acquired liver diseases.

    Science.gov (United States)

    Libbrecht, L; Cassiman, D; Desmet, V; Roskams, T

    2001-09-01

    In the liver, neural cell adhesion molecule (NCAM) is a marker of immature cells committed to the biliary lineage and is expressed by reactive bile ductules in human liver diseases. We investigated the possible role of NCAM in the development of intrahepatic bile ducts and aimed at determining whether immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases. Therefore, we performed immunohistochemistry for NCAM and bile duct cell markers cytokeratin 7 and cytokeratin 19 on frozen sections of 85 liver specimens taken from 14 fetuses, 10 donor livers, 18 patients with congenital liver diseases characterized by ductal plate malformations (DPMs), and 43 cirrhotic explant livers. Duplicated ductal plates and incorporating bile ducts during development showed a patchy immunoreactivity for NCAM, while DPMs were continuously positive for NCAM. Bile ducts showing complete or patchy immunoreactivity for NCAM were found in cirrhotic livers, with higher frequency in biliary than in posthepatitic cirrhosis. Our results suggest that NCAM may have a function in the development of the intrahepatic bile ducts and that NCAM-positive immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases.

  15. Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells

    DEFF Research Database (Denmark)

    Edvardsen, K; Brünner, N; Spang-Thomsen, M

    1993-01-01

    A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared...

  16. Insulin promotes cell migration by regulating PSA-NCAM.

    Science.gov (United States)

    Monzo, Hector J; Coppieters, Natacha; Park, Thomas I H; Dieriks, Birger V; Faull, Richard L M; Dragunow, Mike; Curtis, Maurice A

    2017-06-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Low-level lead exposure attenuates the expression of three major isoforms of neural cell adhesion molecule.

    Science.gov (United States)

    Hu, Qiansheng; Fu, Hongjun; Song, Hong; Ren, Tieling; Li, Liquan; Ye, Liuqing; Liu, Tao; Dong, Shengzhang

    2011-03-01

    Toxic lead (Pb) exposure poses serious risks to human health, especially to children at developmental stages, even at low exposure levels. Neural cell adhesion molecule (NCAM) is considered to be a potential early target in the neurotoxicity of Pb due to its role in cell adhesion, neuronal migration, synaptic plasticity, and learning and memory. However, the effect of low-level Pb exposure on the specific expression of NCAM isoforms has not been reported. In the present study, we found that Pb could concentration-dependently (1-100 nM) inhibit the expression of three major NCAM isoforms (NCAM-180, -140, and -120) in primary cultured hippocampal neurons. Furthermore, it was verified that levels of all three major isoforms of NCAM were reduced by Pb exposure in human embryonic kidney (HEK)-293 cells transiently transfected with NCAM-120, -140, or -180 isoform cDNA constructs. In addition, low-level Pb exposure delayed the neurite outgrowth and reduced the survival rate of cultured hippocampal neurons at different time-points. Together, our results demonstrate that developmental low-level Pb exposure can attenuate the expression of all three major NCAM isoforms, which may contribute to the observed Pb-mediated neurotoxicity. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Post-Training Intrahippocampal Injection of Synthetic Poly-Alpha-2,8-Sialic Acid-Neural Cell Adhesion Molecule Mimetic Peptide Improves Spatial Long-Term Performance in Mice

    Science.gov (United States)

    Florian, Cedrick; Foltz, Jane; Norreel, Jean-Chretien; Rougon, Genevieve; Roullet, Pascal

    2006-01-01

    Several data have shown that the neural cell adhesion molecule (NCAM) is necessary for long-term memory formation and might play a role in the structural reorganization of synapses. The NCAM, encoded by a single gene, is represented by several isoforms that differ with regard to their content of alpha-2,8-linked sialic acid residues (PSA) on their…

  19. Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells

    DEFF Research Database (Denmark)

    Edvardsen, K; Brünner, N; Spang-Thomsen, M

    1993-01-01

    A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared...... to cells transfected with expression-vector alone or untransfected cells. However, when injected subcutaneously into nude mice, both NCAM expressing cells and control cells produced invasive tumors. Nude mice injected with NCAM positive cells developed tumors with slower growth rates as compared to those...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here...... been demonstrated in muscle cell lines and in primary cultures of muscle cells during formation of myotubes in vitro, and this switch in NCAM mRNA classes has been suggested to correlate with myogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)...

  1. Down-regulation of the axonal PSA-NCAM expression coincides with the onset of myelination in the human fetal forebrain

    OpenAIRE

    Jakovcevski, Igor; Mo, Zhicheng; Zecevic, Nada

    2007-01-01

    The polysialic acid (PSA) modification of neural cell adhesion molecule, which reduces NCAM-mediated cell adhesion, is involved in several developmental processes, such as cell migration, axonal growth, pathfinding, and synaptic plasticity. It has been suggested that PSA-NCAM expression may inhibit myelination. To clarify the relationship between myelination and the expression of PSA-NCAM we systematically investigated its expression in the human forebrain from embryonic stage to midgestation...

  2. Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Møller, C; Bock, E

    1992-01-01

    characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

  3. Identification of an amino acid sequence motif in the cytoplasmic domain of the NCAM-140 kDa isoform essential for its neuritogenic activity

    DEFF Research Database (Denmark)

    Kolkova, K; Pedersen, N; Berezin, V

    2000-01-01

    The functions of the extracellular domains of neural cell adhesion molecule (NCAM) have been studied extensively, whereas the roles of the cytoplasmic domains of the transmembrane forms of NCAM are less elucidated. We investigated the importance of the cytoplasmic domain of the 140-kDa NCAM isoform...... encoding cytNCAM-140, cytNCAM-180, the constitutively active form of the mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase kinase (MEK2), and the enhanced variant of the green fluorescent protein (EGFP). EGFP expression was used for identification of transfected cells. We found...

  4. 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

    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......-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......II. Accordingly, we show that treatment of cerebellar granule neurons (CGNs) with heparin inhibits NCAM-mediated outgrowth. In contrast, treatment with heparinase III or chondroitinase ABC abrogates NCAM-mediated neurite outgrowth in CGNs emphasizing the importance of the presence of heparan/chondroitin sulfates...

  5. 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 mo......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....

  6. Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Møller, C; Bock, E

    1992-01-01

    characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were......Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

  7. NCAM180 regulates Ric8A membrane localization and potentiates β-adrenergic response.

    Directory of Open Access Journals (Sweden)

    Marie-Claude Amoureux

    Full Text Available Cooperation between receptors allows integrated intracellular signaling leading to appropriate physiological responses. The Neural Cell Adhesion Molecule (NCAM has three main isoforms of 120, 140 and 180 kDa, with adhesive and signaling properties, but their respective functions remains to be fully identified. Here we show that the human NCAM180 intracellular domain is a novel interactor of the human guanosine exchange factor (GEF Ric8A using the yeast two hybrid system and immunoprecipitation. Furthermore, NCAM, Ric8A and G(αs form a tripartite complex. Colocalization experiments by confocal microscopy revealed that human NCAM180 specifically induces the recruitment of Ric8A to the membrane. In addition, using an in vitro recombinant system, and in vivo by comparing NCAM knock-out mouse brain to NCAM heterozygous and wild type brains, we show that NCAM expression dose dependently regulates Ric8A redistribution in detergent resistent membrane microdomains (DRM. Previous studies have demonstrated essential roles for Ric8 in G(α protein activity at G protein coupled receptors (GPCR, during neurotransmitter release and for asymmetric cell division. We observed that inhibition of Ric8A by siRNA or its overexpression, decreases or increases respectively, cAMP production following β-adrenergic receptor stimulation. Furthermore, in human HEK293T recombinant cells, NCAM180 potentiates the G(αs coupled β-adrenergic receptor response, in a Ric8A dependent manner, whereas NCAM120 or NCAM140 do not. Finally, in mouse hippocampal neurons expressing endogenously NCAM, NCAM is required for the agonist isoproterenol to induce cAMP production, and this requirement depends on Ric8A. These data illustrate a functional crosstalk between a GPCR and an IgCAM in the nervous system.

  8. Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

    Science.gov (United States)

    Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2018-02-21

    Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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

  10. NCAM2 deletion in a boy with macrocephaly and autism: Cause, association or predisposition?

    Science.gov (United States)

    Scholz, Caroline; Steinemann, Doris; Mälzer, Madeleine; Roy, Mandy; Arslan-Kirchner, Mine; Illig, Thomas; Schmidtke, Jörg; Stuhrmann, Manfred

    2016-10-01

    We report on an 8-year-old boy with autism spectrum disorder (ASD), speech delay, behavioural problems, disturbed sleep and macrosomia including macrocephaly carrying a microdeletion that contains the entire NCAM2 gene and no other functional genes. Other family members with the microdeletion show a large skull circumference but do not exhibit any symptoms of autism spectrum disorder. Among many ASD-candidate genes, NCAM2 has been assumed to play a pivotal role in the development of ASD because of its function in the outgrowth and bundling of neurites. Our reported case raises the questions whether the NCAM2-deletion is the true cause of the ASD or only a risk factor and whether there might be any connection in NCAM2 with skull-size autism spectrum disorder, macrocephaly, neural cell adhesion molecule 2 protein (NCAM2), array comparative genomic hybridization (microarray). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. The Prion Protein Controls Polysialylation of Neural Cell Adhesion Molecule 1 during Cellular Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Mohadeseh Mehrabian

    Full Text Available Despite its multi-faceted role in neurodegenerative diseases, the physiological function of the prion protein (PrP has remained elusive. On the basis of its evolutionary relationship to ZIP metal ion transporters, we considered that PrP may contribute to the morphogenetic reprogramming of cells underlying epithelial-to-mesenchymal transitions (EMT. Consistent with this hypothesis, PrP transcription increased more than tenfold during EMT, and stable PrP-deficient cells failed to complete EMT in a mammalian cell model. A global comparative proteomics analysis identified the neural cell adhesion molecule 1 (NCAM1 as a candidate mediator of this impairment, which led to the observation that PrP-deficient cells fail to undergo NCAM1 polysialylation during EMT. Surprisingly, this defect was caused by a perturbed transcription of the polysialyltransferase ST8SIA2 gene. Proteomics data pointed toward β-catenin as a transcriptional regulator affected in PrP-deficient cells. Indeed, pharmacological blockade or siRNA-based knockdown of β-catenin mimicked PrP-deficiency in regards to NCAM1 polysialylation. Our data established the existence of a PrP-ST8SIA2-NCAM signaling loop, merged two mature fields of investigation and offer a simple model for explaining phenotypes linked to PrP.

  12. Characterization of macrophage adhesion molecule

    International Nuclear Information System (INIS)

    Remold-O'Donnell, E.; Savage, B.

    1988-01-01

    Macrophage adhesion molecule (MAM), an abundant surface molecule which functions in the adhesion and spreading of guinea pig macrophages on surfaces, is characterized as a heterodimer of the trypsin- and plasmin-sensitive glycopeptide gp160 (MAM-α) and the glycopeptide gp93 (MAM-β). The density of MAM molecules is estimated at 630,000 per macrophage on the basis of quantitative binding of 125 I-labeled monoclonal antibody. The glycopeptide subunits display microheterogeneity on isoelectrofocusing; the pI is 5.8-6.3 for gp160 (MAM-α) and 6.4-7.0 for gp93 (MAM-β). A neutrophil gp160, gp93 molecule was shown to be indistinguishable from macrophage MAM on the basis of electrophoresis, isoelectrofocusing, and reactivity with 10 monoclonal antibodies. A related heterodimer of gp93 associated with a larger, antigenically different glycopeptide (gp180, gp93)was identified on circulating lymphocytes. Cumulative properties indicate that MAM is the guinea pig analog of human Mo1 and mouse Mac-1

  13. Neural Cell Adhesion Molecules of the Immunoglobulin Superfamily Regulate Synapse Formation, Maintenance, and Function.

    Science.gov (United States)

    Sytnyk, Vladimir; Leshchyns'ka, Iryna; Schachner, Melitta

    2017-05-01

    Immunoglobulin superfamily adhesion molecules are among the most abundant proteins in vertebrate and invertebrate nervous systems. Prominent family members are the neural cell adhesion molecules NCAM and L1, which were the first to be shown to be essential not only in development but also in synaptic function and as key regulators of synapse formation, synaptic activity, plasticity, and synaptic vesicle recycling at distinct developmental and activity stages. In addition to interacting with each other, adhesion molecules interact with ion channels and cytokine and neurotransmitter receptors. Mutations in their genes are linked to neurological disorders associated with abnormal development and synaptic functioning. This review presents an overview of recent studies on these molecules and their crucial impact on neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Heterogeneity of cell adhesion molecules in the developing nervous system

    International Nuclear Information System (INIS)

    Williams, R.K.

    1985-01-01

    Cell-surface molecules, especially glycoproteins, are believed to mediate interactions between developing neurons and their environment. These interactions include pathfinding by growing processes, recognition of appropriate targets, and formation of synaptic structures. In order to identify neuronal cell-surface molecules, monoclonal antibodies (Mab's) were prepared against synaptic fractions from adult rat brain. From this group three monoclonal antibodies, designated 3C5.59, 3G5.34, and 3G6.41, that react with cell-surface antigens of embryonic neurons were selected for further study. In immunofluoresence experiments each of these antibodies strongly reacted with the processes of cultured granule cell neurons, the major class of small cerebellar neurons, cultured from developing rat cerebellum. Mab's 3C5.59 and 3G5.34 reacted only with neurons in the cerebellar cultures. Mab 3G6.41, however, also reacted with cultured brain astrocytes. On frozen sections Mab's 3G5.34 and 3G6.41 also strongly stained the molecular layer, the site of active granule cell axon growth, in the developing cerebellum. Monoclonal and polyclonal antibodies specific for the neural cell adhesion molecule (N-CAM) were used to compare the two glycoproteins recognized by Mab 3G6.41 with N-CAM. Band 1, another large neuronal cell-surface glycoprotein was originally identified in mouse N18 neuroblastoma cells. In this study 125 I-labeled N18-derived band 1 was tested for binding to 9 plant lectins and Limulus polyphemus agglutinin coupled to agarose beads. Band 1 solubilized from brain also specifically bound to LCA-agarose, indicating that mannose containing sugar moieties are present on band 1 from brain

  15. Role of stress system disturbance and enhanced novelty response in spatial learning of NCAM-deficient mice.

    Science.gov (United States)

    Brandewiede, Joerg; Jakovcevski, Mira; Stork, Oliver; Schachner, Melitta

    2013-11-01

    The neural cell adhesion molecule (NCAM) plays a crucial role in stress-related brain function, emotional behavior and memory formation. In this study, we investigated the functions of the glucocorticoid and serotonergic systems in mice constitutively deficient for NCAM (NCAM-/- mice). Our data provide evidence for a hyperfunction of the hypothalamic-pituitary-adrenal axis, with enlarged adrenal glands and increased stress-induced corticosterone release, but reduced hippocampal glucocorticoid receptor expression in NCAM-/- mice when compared to NCAM+/+ mice. We also obtained evidence for a hypofunction of 5-HT1A autoreceptors as indicated by increased 8-0H-DPAT-induced hypothermia. These findings suggest a disturbance of both humoral and neural stress systems in NCAM-/- mice. Accordingly, we not only confirmed previously observed hyperarousal of NCAM-/- mice in various anxiety tests, but also observed an increased response to novelty exposure in these animals. Spatial learning deficits of the NCAM-/- mice in a Morris Water maze persisted, even when mice were pretrained to prevent effects of novelty or stress. We suggest that NCAM-mediated processes are involved in both novelty/stress-related emotional behavior and in cognitive function during spatial learning.

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

    DEFF Research Database (Denmark)

    Andersson, A M; Moran, N; Gaardsvoll, H

    1991-01-01

    The neural cell adhesion molecule, NCAM, plays an important role in cell-cell adhesion. Therefore, we have studied NCAM expression in the glioma cell lines BT4C and BT4Cn. We demonstrate that the 2 cell lines differ in their metastatic ability; while BT4C cells have a very low capacity...... for producing experimental metastases, that of BT4Cn cells is high. In BT4C cells NCAM is synthesized as 4 polypeptides with Mr's of 190,000, 140,000, 115,000 and 97,000. The 140,000, 115,000 and 97,000 polypeptides are glycosylated and for the 140,000 and 115,000 polypeptides sulfatation is observed....... Conversely, no NCAM protein synthesis is observed in BT4Cn cells, even though NCAM mRNA is expressed. Thus, development of an increased metastatic capacity is accompanied by the disappearance of NCAM protein expression in this model system. The functional importance of NCAM expression was studied by a cell...

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

    DEFF Research Database (Denmark)

    Nybroe, O; Albrechtsen, M; Dahlin, J

    1985-01-01

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

  18. The genetically modified polysialylated form of neural cell adhesion molecule-positive cells for potential treatment of X-linked adrenoleukodystrophy.

    Science.gov (United States)

    Jang, Jiho; Kim, Han-Soo; Kang, Joon Won; Kang, Hoon-Chul

    2013-01-01

    Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.

  19. Expression of cell adhesion molecules in normal nerves, chronic axonal neuropathies and Schwann cell tumors.

    Science.gov (United States)

    Roche, P H; Figarella-Branger, D; Daniel, L; Bianco, N; Pellet, W; Pellissier, J F

    1997-10-22

    Cell adhesion molecules (CAMs) play a role in the normal development and regeneration of tissues as well as in the biological behaviour of tumors. We studied the immunohistochemical expression of various CAMs, such as neural cell adhesion molecule (NCAM), its polysialylated isoform (PSA-NCAM), epithelial (E-) cadherin, and beta1 integrins (alpha2beta1, alpha5beta1, alpha6beta1) in a series of frozen specimens of 10 normal nerves, 5 axonal neuropathies, 26 benign Schwannomas and 2 malignant peripheral nerve sheath tumors (MNST). NCAM was expressed by non-myelinating Schwann cells from normal nerves and overexpressed by Schwann cells from patients with chronic axonal neuropathies and Schwannomas. The expression was lower in MNST. Expression of PSA-NCAM was heterogeneously displayed by Schwann cells from the various tissues studied. Anti E-cadherin immunoreactivity was present in myelin sheath in normal nerves and axonopathies. It was expressed in some Schwannomas especially in vestibular Schwannomas. Integrins VLA alpha2 and VLA alpha6 were widely expressed by Schwann cells from normal nerves, axonal neuropathies and Schwannomas but their expression was low in MNST. VLA alpha5 was not expressed by Schwann cells from normal nerve and Schwannomas but present in chronic axonal neuropathies and MNST. In addition VLA alpha6 was strongly expressed by perineurial cells. These data show that CAMs have a characteristic pattern of expression in normal nerve. Also, some CAMs are always expressed by Schwann cells but the expression of others differs in normal nerves versus axonopathies or tumors, suggesting a role of the microcellular environment in the regulation of CAM expression. Schwannomas have different pattern of expression than MNST.

  20. Regulation of Neural Cell Adhesion Molecule Polysialylation: Evidence for Nontranscriptional Control and Sensitivity to an Intracellular Pool of Calcium

    OpenAIRE

    Brusés, Juan L.; Rutishauser, Urs

    1998-01-01

    The up- and downregulation of polysialic acid–neural cell adhesion molecule (PSA–NCAM) expression on motorneurons during development is associated respectively with target innervation and synaptogenesis, and is regulated at the level of PSA enzymatic biosynthesis involving specific polysialyltransferase activity. The purpose of this study has been to describe the cellular mechanisms by which that regulation might occur. It has been found that developmental regulation of PSA synthesis by cilia...

  1. Morphofunctional plasticity in the adult hypothalamus induces regulation of polysialic acid-neural cell adhesion molecule through changing activity and expression levels of polysialyltransferases.

    Science.gov (United States)

    Soares, S; von Boxberg, Y; Ravaille-Veron, M; Vincent, J D; Nothias, F

    2000-04-01

    Polysialic acid-neural cell adhesion molecule (PSA-NCAM) expression in the adult nervous system is restricted to regions retaining a capacity for morphological plasticity. For the female rat hypothalamoneurohypophysial system (HNS), we have previously shown that lactation induces a dramatic decrease in PSA-NCAM, while leaving the level of total NCAM protein unchanged. Here, we wanted to elucidate the molecular mechanisms leading to a downregulation of PSA, thereby stabilizing newly established synapses and neurohemal contacts that accompany the increased activity of oxytocinergic neurons. First, we show that the overall specific activity of polysialyltransferases present in tissue extracts from supraoptic nuclei decreases by approximately 50% during lactation. So far, two polysialyltransferase enzymes, STX and PST, have been characterized for their capacity to transfer PSA onto NCAM in vitro. Using a competitive RT-PCR on RNA extracts from the HNS, we demonstrate furthermore a significant decrease in the expression levels of both STX and PST mRNAs in lactating versus virgin animals. Interestingly, this downregulation of NCAM polysialylation is not correlated with the post-transcriptional regulation of variable alternative spliced exon splicing, in contrast to neural development. The control of polysialylation via a regulation of both enzyme activity and expression underlines the important role of this post-translational modification of NCAM in morphofunctional plasticity in adult brain.

  2. 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.

  3. Neuroprotective and memory enhancing properties of a dual agonist of the FGF receptor and NCAM

    DEFF Research Database (Denmark)

    Enevoldsen, Maj N; Kochoyan, Artur; Jurgenson, Monika

    2012-01-01

    The fibroblast growth factor receptor (FGFR) plays a vital role in the development of the nervous system regulating a multitude of cellular processes. One of the interaction partners of the FGFR is the neural cell adhesion molecule (NCAM), which is known to play an important role in neuronal deve...

  4. A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study

    DEFF Research Database (Denmark)

    Popov, Victor I; Medvedev, Nikolay I; Kraev, Igor V

    2008-01-01

    The FGL peptide is a neural cell adhesion molecule (NCAM) mimetic comprising a 15-amino-acid-long sequence of the FG loop region of the second fibronectin type III module of NCAM. It corresponds to the binding site of NCAM for the fibroblast growth factor receptor 1. FGL improves cognitive function...... through enhancement of synaptic function. We examined the effect of FGL on synaptic and dendritic structure in the brains of aged (22-month-old) rats that were injected subcutaneously (8 mg/kg) at 2-day intervals until 19 days after the start of the experiment. Animals were perfused with fixative, brains...... structure of synapses and dendritic spines in hippocampus of aged rats, complementing data showing its effect on cognitive processes....

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

    DEFF Research Database (Denmark)

    Hansen, Stine; Li, Shizhong; Bock, Elisabeth

    2008-01-01

    The neural cell adhesion molecule (NCAM) responds to cues in the external environment and transmits signals to the cell through extracellular and intracellular interactions with a number of other signal transduction molecules. One such NCAM interaction partner is the fibroblast growth factor rece...... various FN3 module loop regions, have been identified as FGFR ligands. All four peptides activate FGFR and differentially modulate a number of neuronal functions, such as differentiation, survival, and synaptic changes that are important for learning, memory, and neuronal regeneration....

  6. 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.

  7. Highly pure and expandable PSA-NCAM-positive neural precursors from human ESC and iPSC-derived neural rosettes.

    Directory of Open Access Journals (Sweden)

    Dae-Sung Kim

    Full Text Available Homogeneous culture of neural precursor cells (NPCs derived from human pluripotent stem cells (hPSCs would provide a powerful tool for biomedical applications. However, previous efforts to expand mechanically dissected neural rosettes for cultivation of NPCs remain concerns regarding non-neural cell contamination. In addition, several attempts to purify NPCs using cell surface markers have not demonstrated the expansion capability of the sorted cells. In the present study, we show that polysialic acid-neural cell adhesion molecule (PSA-NCAM is detected in neural rosette cells derived from hPSCs, and employ PSA-NCAM as a marker for purifying expandable primitive NPCs from the neural rosettes. PSA-NCAM-positive NPCs (termed hNPC(PSA-NCAM+ were isolated from the heterogeneous cell population of mechanically harvested neural rosettes using magnetic-based cell sorting. The hNPC(PSA-NCAM+ extensively expressed neural markers such as Sox1, Sox2, Nestin, and Musashi-1 (80∼98% of the total cells and were propagated for multiple passages while retaining their primitive characteristics in our culture condition. Interestingly, PSA-NCAM-negative cells largely exhibited characteristics of neural crest cells. The hNPC(PSA-NCAM+ showed multipotency and responsiveness to instructive cues towards region-specific neuronal subtypes in vitro. When transplanted into the rat striatum, hNPC(PSA-NCAM+ differentiated into neurons, astrocytes, and oligodendrocytes without particular signs of tumorigenesis. Furthermore, Ki67-positive proliferating cells and non-neural lineage cells were rarely detected in the grafts of hNPC(PSA-NCAM+ compared to those of neural rosette cells. Our results suggest that PSA-NCAM-mediated cell isolation provides a highly expandable population of pure primitive NPCs from hPSCs that will lend themselves as a promising strategy for drug screening and cell therapy for neurodegenerative disorders.

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

    DEFF Research Database (Denmark)

    Klementiev, B; Novikova, T; Korshunova, Irina

    2008-01-01

    The neural cell adhesion molecule (NCAM) plays a crucial role during development and regeneration of the nervous system, mediating neuronal differentiation, survival and plasticity. Moreover, NCAM regulates learning and memory. A peptide termed P2, corresponding to a 12-amino-acid sequence...... significantly improved postlesion recovery of motor and cognitive function, reduced neuronal degeneration, protected cells against oxidative stress, and increased reactive astrogliosis and neuronal plasticity in the sublesional area. P2 appeared rapidly in blood and cerebrospinal fluid after subcutaneous...

  9. 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

    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......, induction of neurites by the C3 peptide was abrogated. These findings suggest that the neuritogenic effect of the C3 peptide requires the presence of functional FGFRs and support the hypothesis that FGFRs are essential in cell adhesion molecule-stimulated neurite outgrowth. The C3 peptide appears...

  10. The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Cattaneo, Paola; Berezin, Vladimir

    2009-01-01

    Neural cell adhesion molecule (NCAM) associates with fibroblast growth factor (FGF) receptor-1 (FGFR1). However, the biological significance of this interaction remains largely elusive. In this study, we show that NCAM induces a specific, FGFR1-mediated cellular response that is remarkably...... in a specific cellular response. Besides introducing a further level of complexity in the regulation of FGFR1 function, our findings highlight the link of FGFR recycling with sustained signaling and cell migration and the critical role of these events in dictating the cellular response evoked by receptor...

  11. 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.

  12. Leukocyte Adhesion Molecules in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Kousuke Noda

    2012-01-01

    Full Text Available Diabetes is a systemic disease that causes a number of metabolic and physiologic abnormalities. One of the major microvascular complications of diabetes is diabetic retinopathy (DR, a leading cause of blindness in people over age 50. The mechanisms underlying the development of DR are not fully understood; however, extensive studies have recently implicated chronic, low-grade inflammation in the pathophysiology of DR. During inflammation leukocytes undergo sequential adhesive interactions with endothelial cells to migrate into the inflamed tissues, a process known as the “leukocyte recruitment cascade” which is orchestrated by precise adhesion molecule expression on the cell surface of leukocytes and the endothelium. This paper summarizes the recent clinical and preclinical works on the roles of leukocyte adhesion molecules in DR.

  13. Identification of NCAM that interacts with the PHE-CoV spike protein.

    Science.gov (United States)

    Gao, Wei; He, Wenqi; Zhao, Kui; Lu, Huijun; Ren, Wenzhi; Du, Chongtao; Chen, Keyan; Lan, Yungang; Song, Deguang; Gao, Feng

    2010-09-24

    The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. We identified Neural Cell Adhesion Molecule (NCAM) as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.

  14. Identification of NCAM that interacts with the PHE-CoV spike protein

    Directory of Open Access Journals (Sweden)

    Chen Keyan

    2010-09-01

    Full Text Available Abstract Background The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. Results We identified Neural Cell Adhesion Molecule (NCAM as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. Conclusions A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.

  15. Functional cross-talk between the cellular prion protein and the neural cell adhesion molecule is critical for neuronal differentiation of neural stem/precursor cells.

    Science.gov (United States)

    Prodromidou, Kanella; Papastefanaki, Florentia; Sklaviadis, Theodoros; Matsas, Rebecca

    2014-06-01

    Cellular prion protein (PrP) is prominently expressed in brain, in differentiated neurons but also in neural stem/precursor cells (NPCs). The misfolding of PrP is a central event in prion diseases, yet the physiological function of PrP is insufficiently understood. Although PrP has been reported to associate with the neural cell adhesion molecule (NCAM), the consequences of concerted PrP-NCAM action in NPC physiology are unknown. Here, we generated NPCs from the subventricular zone (SVZ) of postnatal day 5 wild-type and PrP null (-/-) mice and observed that PrP is essential for proper NPC proliferation and neuronal differentiation. Moreover, we found that PrP is required for the NPC response to NCAM-induced neuronal differentiation. In the absence of PrP, NCAM not only fails to promote neuronal differentiation but also induces an accumulation of doublecortin-positive neuronal progenitors at the proliferation stage. In agreement, we noted an increase in cycling neuronal progenitors in the SVZ of PrP-/- mice compared with PrP+/+ mice, as evidenced by double labeling for the proliferation marker Ki67 and doublecortin as well as by 5-bromo-2'-deoxyuridine incorporation experiments. Additionally, fewer newly born neurons were detected in the rostral migratory stream of PrP-/- mice. Analysis of the migration of SVZ cells in microexplant cultures from wild-type and PrP-/- mice revealed no differences between genotypes or a role for NCAM in this process. Our data demonstrate that PrP plays a critical role in neuronal differentiation of NPCs and suggest that this function is, at least in part, NCAM-dependent. © 2014 AlphaMed Press.

  16. 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.

  17. 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.

  18. Polysialylation of NCAM characterizes the proliferation period of contractile elements during postnatal development of the epididymis.

    Directory of Open Access Journals (Sweden)

    Peter Simon

    Full Text Available Polysialic acid (polySia attached to the neural cell adhesion molecule (NCAM regulates inter alia the proliferation and differentiation via the interactions with neurotrophins. Since in postnatal epididymis neurotrophins and their receptors like the Low-Affinity Nerve Growth Factor Receptor p75 and TrK B receptor are expressed, we wanted to analyze if the polysialylation of NCAM is also involved during the development of the epididymis. To this end, we monitored the developmental changes in the expression of the polysialyltransferases and NCAM polysialylation using murine epididymis at different time points during postnatal development. Our results revealed that during postnatal development of the epididymis both polysialyltransferases, ST8SiaII and ST8SiaIV, were expressed and that the expression levels dropped with increasing age. In agreement with the expression levels of the polysialyltransferases the highest content of polysialylated NCAM was present during the first 10 days after birth. Interestingly, proliferating smooth muscle cell populations prevalently expressed polysialylated NCAM. Furthermore, we observed that inverse to the decrease in polysialylation of smooth muscle cells a strong up-regulation of collagen takes place suggesting a functional relationship since collagen was recently described to induce the turnover of polysialylated NCAM via an induction of endocytosis in cellulo. The same time course of polySia and collagen synthesis was also observed in other regions of the male reproductive system e.g. vas deferens and tunica albuginea (testis. Together, we identified a spatio-temporal expression pattern of polySia-NCAM characterized by high proliferation rate of smooth muscle cells and low collagen content.

  19. PSA-NCAM expression in the teleost optic tectum is related to ecological niche and use of vision in finding food.

    Science.gov (United States)

    Labak, I; Pavić, V; Zjalić, M; Blažetić, S; Viljetić, B; Merdić, E; Heffer, M

    2017-08-01

    In this study, tangential migration and neuronal connectivity organization were analysed in the optic tectum of seven different teleosts through the expression of polysialylated neural cell adhesion molecule (PSA-NCAM) in response to ecological niche and use of vision. Reduced PSA-NCAM expression in rainbow trout Oncorhynchus mykiss optic tectum occurred in efferent layers, while in pike Esox lucius and zebrafish Danio rerio it occurred in afferent and efferent layers. Zander Sander lucioperca and European eel Anguilla anguilla had very low PSA-NCAM expression in all tectal layers except in the stratum marginale. Common carp Cyprinus carpio and wels catfish Silurus glanis had the same intensity of PSA-NCAM expression in all tectal layers. The optic tectum of all studied fishes was also a site of tangential migration with sustained PSA-NCAM and c-series ganglioside expression. Anti-c-series ganglioside immunoreactivity was observed in all tectal layers of all analysed fishes, even in layers where PSA-NCAM expression was reduced. Since the optic tectum is indispensable for visually guided prey capture, stabilization of synaptic contact and decrease of neurogenesis and tangential migration in the visual map are an expected adjustment to ecological niche. The authors hypothesize that this stabilization would probably be achieved by down-regulation of PSA-NCAM rather than c-series of ganglioside. © 2017 The Fisheries Society of the British Isles.

  20. 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

    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...

  1. Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly

    Directory of Open Access Journals (Sweden)

    G.A. Mendes

    2017-12-01

    Full Text Available Pituitary adenomas account for 10–15% of primary intracranial tumors. Growth hormone (GH-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross–sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at –80°C for assessment of E-cadherin 1 (CDH1, SLUG (SNAI2, and NCAM (NCAM1 by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.

  2. Vascular adhesion molecules in oral lichen planus.

    Science.gov (United States)

    Regezi, J A; Dekker, N P; MacPhail, L A; Lozada-Nur, F; McCalmont, T H

    1996-06-01

    Because recruitment and retention of lymphoid cells appear to be critical components of the pathogenesis of lichen planus, we have compared the expression and distribution of a panel of vascular adhesion molecules (ELAM-1, P-selectin, ICAM-1, VCAM-1, PECAM-1, CD34) and leukocyte adhesion molecule ligands (LFA-1, Mac-1, VLA4, L-selectin) in biopsies of this disease. Frozen sections of 12 clinically and histologically confirmed cases of lichen planus and 9 normal control tissues were evaluated immunohistochemically with a standard 1-day avidin-biotin peroxidase technique. Staining intensity of vascular endothelium was evaluated semiquantitatively. Three microvascular zones or compartments were defined and evaluated separately. Generally, different staining patterns were observed in association with the various endothelium-associated adhesion molecules. In normal controls, PECAM was intensely expressed and VCAM-1 was weakly expressed. Intermediate staining was associated with ELAM-1, P-selectin, ICAM-1, and CD34. Staining within the three microvascular compartments frequently showed variations in intensity. In lichen planus, increased staining for ELAM-1, P-selectin, ICAM-1, and VCAM-1 was evident in one or more of the microvascular compartments. In the subepithelial vascular compartment where the infiltrate was the most dense, VCAM-1 appeared to show the greatest positive change. Almost all cells in the lichen planus infiltrates stained positive for ICAM-1, L-selectin, LFA-1, and VLA4, and large numbers of cells also exhibited VCAM-1, PECAM-1, and Mac-1 immunoreactivity. It appears that upregulation of ELAM-1, ICAM-1, and VCAM-1 (especially by endothelial cells in the subepithelial vascular plexus) could play a role in the pathogenesis of lichen planus. The expression of leukocyte receptors L-selectin, LFA-1, and VLA4 by most of the cells in the lichen planus infiltrate suggest that these molecules may be responsible for recruitment as well as retention in the active

  3. A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation

    DEFF Research Database (Denmark)

    Downer, Eric J; Cowley, Thelma R; Cox, Fionnuala

    2009-01-01

    Microglial cell activity increases in the rat hippocampus during normal brain aging. The neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as an anti-inflammatory agent in the hippocampus of the aged rat, promoting CD200 ligand expression while attenuating glial cell...

  4. Organization of central synapses by adhesion molecules.

    Science.gov (United States)

    Tallafuss, Alexandra; Constable, John R L; Washbourne, Philip

    2010-07-01

    Synapses are the primary means for transmitting information from one neuron to the next. They are formed during the development of the nervous system, and the formation of appropriate synapses is crucial for the establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies have revealed a diverse and vast assortment of molecules that are present at the synapse. It is now important to untangle this large array of proteins and determine how it assembles into a functioning unit. Here we focus on recent reports describing how synaptic cell adhesion molecules interact with and organize the presynaptic and postsynaptic specializations of both excitatory and inhibitory central synapses. © The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. Intercellular adhesion molecules (ICAMs) and spermatogenesis

    Science.gov (United States)

    Xiao, Xiang; Mruk, Dolores D.; Cheng, C. Yan

    2013-01-01

    BACKGROUND During the seminiferous epithelial cycle, restructuring takes places at the Sertoli–Sertoli and Sertoli–germ cell interface to accommodate spermatogonia/spermatogonial stem cell renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation since developing germ cells, in particular spermatids, move ‘up and down’ the seminiferous epithelium. Furthermore, preleptotene spermatocytes differentiated from type B spermatogonia residing at the basal compartment must traverse the blood–testis barrier (BTB) to enter the adluminal compartment to prepare for meiosis at Stage VIII of the epithelial cycle, a process also accompanied by the release of sperm at spermiation. These cellular events that take place at the opposite ends of the epithelium are co-ordinated by a functional axis designated the apical ectoplasmic specialization (ES)—BTB—basement membrane. However, the regulatory molecules that co-ordinate cellular events in this axis are not known. METHODS Literature was searched at http://www.pubmed.org and http://scholar.google.com to identify published findings regarding intercellular adhesion molecules (ICAMs) and the regulation of this axis. RESULTS Members of the ICAM family, namely ICAM-1 and ICAM-2, and the biologically active soluble ICAM-1 (sICAM-1) are the likely regulatory molecules that co-ordinate these events. sICAM-1 and ICAM-1 have antagonistic effects on the Sertoli cell tight junction-permeability barrier, involved in Sertoli cell BTB restructuring, whereas ICAM-2 is restricted to the apical ES, regulating spermatid adhesion during the epithelial cycle. Studies in other epithelia/endothelia on the role of the ICAM family in regulating cell movement are discussed and this information has been evaluated and integrated into studies of these proteins in the testis to create a hypothetical model, depicting how ICAMs regulate junction restructuring events during spermatogenesis. CONCLUSIONS ICAMs are crucial

  6. Intercellular adhesion molecules (ICAMs) and spermatogenesis.

    Science.gov (United States)

    Xiao, Xiang; Mruk, Dolores D; Cheng, C Yan

    2013-01-01

    During the seminiferous epithelial cycle, restructuring takes places at the Sertoli-Sertoli and Sertoli-germ cell interface to accommodate spermatogonia/spermatogonial stem cell renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation since developing germ cells, in particular spermatids, move 'up and down' the seminiferous epithelium. Furthermore, preleptotene spermatocytes differentiated from type B spermatogonia residing at the basal compartment must traverse the blood-testis barrier (BTB) to enter the adluminal compartment to prepare for meiosis at Stage VIII of the epithelial cycle, a process also accompanied by the release of sperm at spermiation. These cellular events that take place at the opposite ends of the epithelium are co-ordinated by a functional axis designated the apical ectoplasmic specialization (ES)-BTB-basement membrane. However, the regulatory molecules that co-ordinate cellular events in this axis are not known. Literature was searched at http://www.pubmed.org and http://scholar.google.com to identify published findings regarding intercellular adhesion molecules (ICAMs) and the regulation of this axis. Members of the ICAM family, namely ICAM-1 and ICAM-2, and the biologically active soluble ICAM-1 (sICAM-1) are the likely regulatory molecules that co-ordinate these events. sICAM-1 and ICAM-1 have antagonistic effects on the Sertoli cell tight junction-permeability barrier, involved in Sertoli cell BTB restructuring, whereas ICAM-2 is restricted to the apical ES, regulating spermatid adhesion during the epithelial cycle. Studies in other epithelia/endothelia on the role of the ICAM family in regulating cell movement are discussed and this information has been evaluated and integrated into studies of these proteins in the testis to create a hypothetical model, depicting how ICAMs regulate junction restructuring events during spermatogenesis. ICAMs are crucial regulatory molecules of spermatogenesis. The proposed

  7. Epithelial cell adhesion molecule - More than a carcinoma marker and adhesion molecule

    NARCIS (Netherlands)

    Trzpis, Monika; McLaughlin, Pamela M. J.; de Leij, Lou M. F. H.; Harmsen, Martin C.

    The epithetial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of similar to 40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally

  8. Bacterial Vaginosis Bacterial and Epithelial Cell Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    Şayeste Demirezen

    2016-05-01

    molecules. The most important adhesion molecules of epithelium are cadherins, fibronectins, Toll like receptors and carbohydrates. In bacteria, pilis, lypopolysaccaharide and biofilm have primary importance. In this review, the adhesion molecules are discussed in detail and their roles in formation of clue cell are clarified.

  9. 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....

  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. The influence of tobacco smoking on adhesion molecule profiles

    Directory of Open Access Journals (Sweden)

    Palmer RM

    2003-01-01

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

  12. The influence of tobacco smoking on adhesion molecule profiles

    Directory of Open Access Journals (Sweden)

    Palmer RM

    2002-01-01

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

  13. 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...

  14. Maternal low-level lead exposure reduces the expression of PSA-NCAM and the activity of sialyltransferase in the hippocampi of neonatal rat pups.

    Science.gov (United States)

    Hu, Qiansheng; Fu, Hongjun; Ren, Tieling; Wang, Shuyu; Zhou, Wei; Song, Hong; Han, Yifan; Dong, Shengzhang

    2008-07-01

    Highly polysialylated neural cell adhesion molecule (PSA-NCAM) is transiently expressed specifically in newly generated cells, and is important for cell migration and neurite outgrowth. Developmental lead (Pb) exposure has been considered to affect the expression of PSA-NCAM, which contributes to the neurotoxicity of Pb exposure. However, the effect of maternal low-level Pb exposure on the expression of PSA-NCAM in neonatal rat pups has not been reported. In the present study, female Wistar rats were exposed to vehicle or different dosages of lead chloride (0.5-4mM PbCl2) 2 weeks before and during pregnancy. This exposure protocol resulted in neonatal rat pups blood Pb levels up to 12.12+/-0.38 microg/dl, and hippocampal Pb levels up to 9.22+/-0.81 microg/g at postnatal day 1 (PND 1). Immunohistochemistry analysis and Western blot analysis revealed that the expressions of PSA-NCAM and NCAM in the hippocampi of neonatal rat pups at PND 1 were significantly reduced by the maternal low-level Pb exposures. Furthermore, the mRNA levels of NCAM and polysialyltransferases (STX and PST), measured by the fluorescent real-time quantitative RT-PCR, dosage-dependently and significantly decreased by 13.26-37.62%, 25.17-59.67%, and 10.78-47.81%, respectively. In addition, the sialyltransferase activity in neonatal rat pups was significantly reduced by 6.23-32.50% in the presence of the low-level Pb exposure, too. Taken together, these results suggest that maternal low-level Pb exposure reduces the expression of PSA-NCAM, NCAM, and the activity of sialyltransferase in the hippocampi of neonatal rat pups, which might contribute to the learning and memory impairments in the developmental pups following maternal low-level Pb exposure.

  15. Overexpression of Polysialylated Neural Cell Adhesion Molecule Improves the Migration Capacity of Induced Pluripotent Stem Cell-Derived Oligodendrocyte Precursors

    Science.gov (United States)

    Czepiel, Marcin; Leicher, Lasse; Becker, Katja; Boddeke, Erik

    2014-01-01

    Cell replacement therapy aiming at the compensation of lost oligodendrocytes and restoration of myelination in acquired or congenital demyelination disorders has gained considerable interest since the discovery of induced pluripotent stem cells (iPSCs). Patient-derived iPSCs provide an inexhaustible source for transplantable autologous oligodendrocyte precursors (OPCs). The first transplantation studies in animal models for demyelination with iPSC-derived OPCs demonstrated their survival and remyelinating capacity, but also revealed their limited migration capacity. In the present study, we induced overexpression of the polysialylating enzyme sialyltransferase X (STX) in iPSC-derived OPCs to stimulate the production of polysialic acid-neuronal cell adhesion molecules (PSA-NCAMs), known to promote and facilitate the migration of OPCs. The STX-overexpressing iPSC-derived OPCs showed a normal differentiation and maturation pattern and were able to downregulate PSA-NCAMs when they became myelin-forming oligodendrocytes. After implantation in the demyelinated corpus callosum of cuprizone-fed mice, STX-expressing iPSC-derived OPCs demonstrated a significant increase in migration along the axons. Our findings suggest that the reach and efficacy of iPSC-derived OPC transplantation can be improved by stimulating the OPC migration potential via specific gene modulation. PMID:25069776

  16. Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

    OpenAIRE

    Kong, Qingxia; Min, Xia; Sun, Ran; Gao, Jianying; Liang, Ruqing; Li, Lei; Chu, Xu

    2016-01-01

    The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the...

  17. A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35

    DEFF Research Database (Denmark)

    Klementiev, B; Novikova, T; Novitskaya, V

    2007-01-01

    death and brain atrophy in response to Abeta25-35. Finally, the Abeta25-35-administration led to a reduced short-term memory as determined by the social recognition test. A synthetic peptide termed FGL derived from the neural cell adhesion molecule (NCAM) was able to prevent or, if already manifest......, strongly reduce all investigated signs of Abeta25-35-induced neuropathology and cognitive impairment. The FGL peptide was recently demonstrated to be able to cross the blood-brain-barrier. Accordingly, we found that the beneficial effects of FGL were achieved not only by intracisternal, but also...... and cognitive impairment involves the modulation of intracellular signal-transduction mediated through GSK3beta....

  18. The relation between oxidative stress and adhesion molecules in ...

    African Journals Online (AJOL)

    EL-HAKIM

    The relation between oxidative stress and adhesion molecules in Egyptian children and adolescents with type 1 diabetes mellitus. INTRODUCTION. Type1 diabetic patients usually develop clinically evident microangiopathy later in adolescence although subclinical functional and structural abnormalities precede its.

  19. Adhesion molecule expression in basal cell carcinoma

    NARCIS (Netherlands)

    Verhaegh, M.; Beljaards, R.; Veraart, J.; Hoekzema, R.; Neumann, M.

    1998-01-01

    Basal cell carcinomas (BCCs) are frequently associated with a peritumoral mononuclear infiltrate. Until now, the function of this inflammatory infiltrate and its possible role in the control of tumor growth is unclear. Mechanisms controlling endothelial and target cell adhesiveness for leukocytes

  20. Antibodies against Shigella flexneri adhesion molecule outer ...

    African Journals Online (AJOL)

    Milliana et al. Trop J Pharm Res, February 2017; 16(2): 256. Outer membrane proteins (OMPs) include proteins that mediate the attachment of bacteria to the host cell more closely than do pili [6,7]. A 49.8. kDa Shigella dysenteriae hemagglutinin pili protein that serves as an adhesion protein was found previously [8]. Oral.

  1. Antibodies against Shigella flexneri adhesion molecule outer ...

    African Journals Online (AJOL)

    OMP) as an adhesion factor and examine its ability to cross-react with the OMPs of other Shigella species. Methods: OMP was isolated from the bacterium S. flexneri after shaving the pili using a pili bacterial cutter in a solution of 0.5 ...

  2. The transcription factors CREB and c-Fos play key roles in NCAM-mediated neuritogenesis in PC12-E2 cells

    DEFF Research Database (Denmark)

    Jessen, U; Novitskaya, V; Pedersen, N

    2001-01-01

    roles in this process by estimating NCAM-dependent neurite outgrowth from PC12-E2 cells grown in co-culture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were transiently transfected with expression plasmids encoding wild-type or dominant negative forms of CREB and c-Fos or an activated...... form of the MAPK kinase, MEK2. Alternatively, PC12-E2 cells were treated with arachidonic acid, the cAMP analogue dBcAMP, or protein kinase A (PKA) inhibitors. The negative forms of CREB and c-Fos inhibited neurite outgrowth mediated by NCAM, arachidonic acid, dBcAMP, or MEK2. Neither CREB nor c......The neural cell adhesion molecule (NCAM) stimulates axonal outgrowth by activation of the Ras-mitogen activated protein kinase (MAPK) pathway and by generation of arachidonic acid. We investigated whether the transcription factors, cyclic-AMP response-element binding protein (CREB) and c-Fos play...

  3. Cell Adhesion Molecules and Ubiquitination—Functions and Significance

    Science.gov (United States)

    Homrich, Mirka; Gotthard, Ingo; Wobst, Hilke; Diestel, Simone

    2015-01-01

    Cell adhesion molecules of the immunoglobulin (Ig) superfamily represent the biggest group of cell adhesion molecules. They have been analyzed since approximately 40 years ago and most of them have been shown to play a role in tumor progression and in the nervous system. All members of the Ig superfamily are intensively posttranslationally modified. However, many aspects of their cellular functions are not yet known. Since a few years ago it is known that some of the Ig superfamily members are modified by ubiquitin. Ubiquitination has classically been described as a proteasomal degradation signal but during the last years it became obvious that it can regulate many other processes including internalization of cell surface molecules and lysosomal sorting. The purpose of this review is to summarize the current knowledge about the ubiquitination of cell adhesion molecules of the Ig superfamily and to discuss its potential physiological roles in tumorigenesis and in the nervous system. PMID:26703751

  4. Developmental iodine deficiency and hypothyroidism impair neural development in rat hippocampus: involvement of doublecortin and NCAM-180

    Directory of Open Access Journals (Sweden)

    Zhong Jiapeng

    2010-04-01

    Full Text Available Abstract Background Developmental iodine deficiency results in inadequate thyroid hormone (TH, which damages the hippocampus. Here, we explored the roles of hippocampal doublecortin and neural cell adhesion molecule (NCAM-180 in developmental iodine deficiency and hypothyroidism. Methods Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil (PTU-adulterated water (5 ppm or 15 ppm to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day (PN 28. Silver-stained neurons and protein levels of doublecortin and NCAM-180 in several hippocampal subregions were assessed on PN14, PN21, PN28, and PN42. Results The results show that nerve fibers in iodine-deficient and 15 ppm PTU-treated rats were injured on PN28 and PN42. Downregulation of doublecortin and upregulation of NCAM-180 were observed in iodine-deficient and 15 ppm PTU-treated rats from PN14 on. These alterations were irreversible by the restoration of serum TH concentrations on PN42. Conclusion Developmental iodine deficiency and hypothyroidism impair the expression of doublecortin and NCAM-180, leading to nerve fiber malfunction and thus impairments in hippocampal development.

  5. Developmental iodine deficiency and hypothyroidism impair neural development in rat hippocampus: involvement of doublecortin and NCAM-180

    Science.gov (United States)

    2010-01-01

    Background Developmental iodine deficiency results in inadequate thyroid hormone (TH), which damages the hippocampus. Here, we explored the roles of hippocampal doublecortin and neural cell adhesion molecule (NCAM)-180 in developmental iodine deficiency and hypothyroidism. Methods Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil (PTU)-adulterated water (5 ppm or 15 ppm) to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day (PN) 28. Silver-stained neurons and protein levels of doublecortin and NCAM-180 in several hippocampal subregions were assessed on PN14, PN21, PN28, and PN42. Results The results show that nerve fibers in iodine-deficient and 15 ppm PTU-treated rats were injured on PN28 and PN42. Downregulation of doublecortin and upregulation of NCAM-180 were observed in iodine-deficient and 15 ppm PTU-treated rats from PN14 on. These alterations were irreversible by the restoration of serum TH concentrations on PN42. Conclusion Developmental iodine deficiency and hypothyroidism impair the expression of doublecortin and NCAM-180, leading to nerve fiber malfunction and thus impairments in hippocampal development. PMID:20412599

  6. Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

    Science.gov (United States)

    Kong, Qingxia; Min, Xia; Sun, Ran; Gao, Jianying; Liang, Ruqing; Li, Lei; Chu, Xu

    2016-01-01

    The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (Paniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (Paniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment. PMID:27588125

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

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

  9. Levels Of Serum Intercellular And Vascular Adhesion Molecules In ...

    African Journals Online (AJOL)

    The study evaluated the possible significant role of soluble intercellular and vascular adhesion molecule-1 (sICAM-1 and sVCAM-1), sE-selectin and interluekin-1β in development nephropathy in patients with insulin dependent diabetes mellitus (IDDM). This study included 60 patients with type 1 diabetes mellitus (IDDM) ...

  10. Investigating single molecule adhesion by atomic force spectroscopy.

    Science.gov (United States)

    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.

  11. Investigating Single Molecule Adhesion by Atomic Force Spectroscopy

    Science.gov (United States)

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

    2015-01-01

    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. PMID:25867282

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

    Directory of Open Access Journals (Sweden)

    Rajabzadeh Aliakbar

    2012-05-01

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

  13. Learning-associated regulation of polysialylated neural cell adhesion molecule expression in the rat prefrontal cortex is region-, cell type- and paradigm-specific.

    Science.gov (United States)

    Ter Horst, Judith P F; Loscher, Jennifer S; Pickering, Mark; Regan, Ciaran M; Murphy, Keith J

    2008-08-01

    The prefrontal cortex (PFC) is an interconnected set of cortical areas that function in the synthesis of a diverse range of information and production of complex behaviour. It is now clear that these frontal structures, through bidirectional excitatory communication with the hippocampal formation, also play a substantial role in long-term memory consolidation. In the hippocampus, morphological synaptic plasticity, supported by regulation of neural cell adhesion molecule (NCAM) polysialylation status, is crucial to information storage. The recent description of polysialylated neurons in the various fields of the medial PFC suggests these structures to possess a similar capacity for synaptic plasticity. Here, using double-labelling immunohistochemistry with glutamic acid decarboxylase 67, we report that the nature of NCAM polysialic acid-positive neurons in the PFC is region-specific, with a high proportion (30-50%) of a gamma-aminobutyric acid (GABA)ergic phenotype in the more ventral infralimbic, orbitofrontal and insular cortices compared with just 10% in the dorsal structures of the cingulate, prelimbic and frontal cortices. Moreover, spatial learning was accompanied by activations in polysialylation expression in ventral PFC structures, while avoidance conditioning involved downregulation of this plasticity marker that was restricted to the dorsomedial PFC--the cingulate and prelimbic cortices. Thus, in contrast to other structures integrated functionally with the hippocampus, memory-associated plasticity mobilized in the PFC is region-, cell type- and task-specific.

  14. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    of combinatorial peptide libraries. The C3 and NBP10 peptides target the first Ig module whereas the ENFIN2 and ENFIN11 peptides target fibronectin type III (FN3) modules of NCAM. A number of NCAM mimetics can induce neurite outgrowth and exhibit neuroprotective and synaptic plasticity modulating properties...

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

    NARCIS (Netherlands)

    Tudor, Cicerone; te Riet, J.; Eich, C.; Harkes, R.; Smisdom, N.; Bouhuijzen Wenger, J.; Ameloot, M.; Holt, M.; Kanger, Johannes S.; Figdor, Carl; Cambi, A.; Subramaniam, Vinod

    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

  16. Post-training intrahippocampal injection of synthetic poly-alpha-2,8-sialic acid-neural cell adhesion molecule mimetic peptide improves spatial long-term performance in mice.

    Science.gov (United States)

    Florian, Cédrick; Foltz, Jane; Norreel, Jean-Chrétien; Rougon, Geneviève; Roullet, Pascal

    2006-01-01

    Several data have shown that the neural cell adhesion molecule (NCAM) is necessary for long-term memory formation and might play a role in the structural reorganization of synapses. The NCAM, encoded by a single gene, is represented by several isoforms that differ with regard to their content of alpha-2,8-linked sialic acid residues (PSA) on their extracellular domain. The carbohydrate PSA is known to promote plasticity, and PSA-NCAM isoforms remain expressed in the CA3 region of the adult hippocampus. In the present study, we investigated the effect on spatial memory consolidation of a PSA gain of function by injecting a PSA mimetic peptide (termed pr2) into the dorsal hippocampus. Mice were subjected to massed training in the spatial version of the water maze. Five hours after the last training session, experimental mice received an injection of pr2, whereas control mice received PBS or reverse peptide injections in the hippocampal CA3 region. Memory retention was tested at different time intervals: 24 h, 1 wk, and 4 wk. The results showed that the post-training infusion of pr2 peptide significantly increases spatial performance whenever it was assessed after the training phase. By contrast, administration of the control reverse peptide did not affect retention performance. These findings provide evidence that (1) PSA-NCAM is involved in memory consolidation processes in the CA3 hippocampal region, and (2) PSA mimetic peptides can facilitate the formation of long-term spatial memory when injected during the memory consolidation phase.

  17. Enzymatic removal of polysialic acid from neural cell adhesion molecule interrupts gonadotropin releasing hormone (GnRH) neuron-glial remodeling.

    Science.gov (United States)

    Kumar, Sushil; Parkash, Jyoti; Kataria, Hardeep; Kaur, Gurcharan

    2012-01-02

    There is abundant evidence to prove that the astrocytes are highly dynamic cell type in CNS and under physiological conditions such as reproduction, these cells display a remarkable structural plasticity especially at the level of their distal processes ensheathing the gonadotropin releasing hormone (GnRH) axon terminals. The morphology of GnRH axon terminals and astrocytes in the median eminence region of hypothalamus show activity dependent structural plasticity during different phases of estrous cycle. In the current study, we have assessed the functional contribution of ∞-2,8-linked polysialic acid (PSA) on neural cell adhesion molecule (PSA-NCAM) in this neuronal-glial plasticity using both in vitro and in vivo model systems. In vivo experiments were carried out after stereotaxic injection of endoneuraminidase enzyme (endo-N) near median eminence region of hypothalamus to specifically remove PSA residues on NCAM followed by localization of GnRH, PSA-NCAM and glial fibrillary acidic protein (GFAP) by immunostaining. Using in vitro model, structural remodeling of GnV-3 cells, (a conditionally immortalized GnRH cell line) co-cultured with primary astrocytes was studied after treating the cells with endo-N. Marked morphological changes were observed in GnRH axon terminals in proestrous phase rats and control GnV-3 cells as compared to endo-N treatment i.e. after removal of PSA. The specificity of endo-N treatment was also confirmed by studying the expression of PSA-NCAM by Western blotting in cultures treated with and without endo-N. Removal of PSA from surfaces with endo-N prevented stimulation associated remodeling of GnRH axon terminals as well as their associated glial cells under both in vivo and in vitro conditions. The current data confirms the permissive role of PSA to promote dynamic remodeling of GnRH axon terminals and their associated glia during reproductive cycle in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Macrophages and vascular adhesion molecules in oral Kaposi's sarcoma.

    Science.gov (United States)

    MacPhail, L A; Dekker, N P; Regezi, J A

    1996-10-01

    Kaposi's sarcoma (KS) is a heterogeneous tumor where spindle cells are predominant and macrophages and factor XIIIa positive dendrocytes are abundant. The origin of the macrophages and dendrocytes is unclear, although their numbers suggest a critical role in KS pathogenesis. To determine if KS macrophages are recruited from the blood stream or proliferate on-site, we examined biopsy specimens 1) for expression and distribution of vascular adhesion molecules (PECAM-1, ELAM-1, ICAM-1, VCAM-1, P-selectin, L-selectin) and the macrophage-associated adhesion-molecule ligand, VLA-4; 2) for dual expression of proliferation (Ki-67) and lineage-associated markers (KP-1, CD34, factor XIIIa, LCA); and 3) for dual expression of macrophage (KP-1) and endothelial cell (CD34) associated markers. Avidinbiotin peroxidase techniques were used. Resident vessels were found to strongly express PECAM-1, ELAM-1, ICAM-1, P-selectin, and moderately express VCAM-1 and VLA-4. Tumor spindle cells showed less intense expression of ELAM-1, ICAM-1 and P-selectin. The most frequent double-stain combination was Ki-67 + CD34+. In contrast, the combinations of Ki-67 + KP-1+, Ki-67 + XIIIa+ and Ki-67 + LCA+ were rarely seen. The enhanced expression of adhesion molecules on resident vessels and the lack of evidence of macrophage proliferation suggest that the abundant macrophages in KS are recruited from the blood stream.

  19. Intercellular adhesion molecule-1 (ICAM-1, CD54) is increased in adhesive capsulitis.

    Science.gov (United States)

    Kim, Yang-Soo; Kim, Jung-Man; Lee, Yun-Gyoung; Hong, Oak-Kee; Kwon, Hyuk-Sang; Ji, Jong-Hoon

    2013-02-20

    The purpose of this study was to investigate the presence of intercellular adhesion molecule-1 (ICAM-1) in shoulders with adhesive capsulitis ("frozen shoulder"). Glenohumeral capsular tissue was obtained from twenty-six patients (seventeen with adhesive capsulitis and nine controls), and ICAM-1 was evaluated with use of oligonucleotide arrays, real-time reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry. ICAM-1 was also evaluated in synovial fluid with use of western blotting (six patients with adhesive capsulitis and two controls) and in peripheral blood with use of an enzyme-linked immunosorbent assay (ELISA) (thirty-two patients with adhesive capsulitis, twenty with diabetes mellitus, and fourteen controls). The effect of ICAM-1 treatment on gene expression of cytokines related to inflammation and fibrosis was evaluated in cultured normal human synovial cells. The level of ICAM-1 was significantly greater in capsular tissue from the glenohumeral joint of patients with adhesive capsulitis compared with controls as measured by oligonucleotide array analysis (0.12 ± 0.01 compared with 0.09 ± 0.00 arbitrary units) (p = 0.001), real-time RT-PCR (1.70 ± 0.19 compared with 0.67 ± 0.24 arbitrary units) (p adhesive capsulitis (1.70 ± 0.18 arbitrary units) compared with normal controls (0.48 ± 0.17) (p adhesive capsulitis (633.22 ± 59.14 ng/mL) and patients with diabetes mellitus (671.25 ± 27.08 ng/mL) compared with controls (359.86 ± 44.29 ng/mL) (p adhesive capsulitis, similar to the increase that has been reported in patients with diabetes mellitus.

  20. Regulation of neural cell adhesion molecule polysialylation: evidence for nontranscriptional control and sensitivity to an intracellular pool of calcium.

    Science.gov (United States)

    Brusés, J L; Rutishauser, U

    1998-03-09

    The up- and downregulation of polysialic acid-neural cell adhesion molecule (PSA-NCAM) expression on motorneurons during development is associated respectively with target innervation and synaptogenesis, and is regulated at the level of PSA enzymatic biosynthesis involving specific polysialyltransferase activity. The purpose of this study has been to describe the cellular mechanisms by which that regulation might occur. It has been found that developmental regulation of PSA synthesis by ciliary ganglion motorneurons is not reflected in the levels of polysialyltransferase-1 (PST) or sialyltransferase-X (STX) mRNA. On the other hand, PSA synthesis in both the ciliary ganglion and the developing tectum appears to be coupled to the concentration of calcium in intracellular compartments. This study documents a calcium dependence of polysialyltransferase activity in a cell-free assay over the range of 0.1-1 mM, and a rapid sensitivity of new PSA synthesis, as measured in a pulse-chase analysis of tissue explants, to calcium ionophore perturbation of intracellular calcium levels. Moreover, the relevant calcium pool appears to be within a specific intracellular compartment that is sensitive to thapsigargin and does not directly reflect the level of cytosolic calcium. Perturbation of other major second messenger systems, such as cAMP and protein kinase-dependent pathways, did not affect polysialylation in the pulse chase analysis. These results suggest that the shuttling of calcium to different pools within the cell can result in the rapid regulation of PSA synthesis in developing tissues.

  1. Junctional adhesion molecule-A: functional diversity through molecular promiscuity.

    Science.gov (United States)

    Steinbacher, Tim; Kummer, Daniel; Ebnet, Klaus

    2017-12-14

    Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell-cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Nevertheless, JAM-A is involved in a variety of biological processes. The functional diversity of JAM-A resides to a large part in a C-terminal PDZ domain binding motif which directly interacts with nine different PDZ domain-containing proteins. The molecular promiscuity of its PDZ domain motif allows JAM-A to recruit protein scaffolds to specific sites of cell-cell adhesion and to assemble signaling complexes at those sites. Here, we review the molecular characteristics of JAM-A, including its dimerization, its interaction with scaffolding proteins, and the phosphorylation of its cytoplasmic domain, and we describe how these characteristics translate into diverse biological activities.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Function of adhesion molecules lymphocyte function-associated antigen-3 and intercellular adhesion molecule-1 on human epidermal Langerhans cells in antigen-specific T cell activation

    NARCIS (Netherlands)

    Teunissen, M. B.; Rongen, H. A.; Bos, J. D.

    1994-01-01

    In addition to the interaction between the TCR and the MHC/Ag complex on the APC, optimal T cell activation also requires interaction between adhesion molecules on the APC and their ligands on T cells. We determined the presence of adhesion molecules on human epidermal Langerhans cells (LC) and

  4. Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Hyoung-Gon Ko

    2018-01-01

    Full Text Available Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1 is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment.

  5. Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after Peripheral Nerve Injury.

    Science.gov (United States)

    Ko, Hyoung-Gon; Choi, Jun-Hyeok; Park, Dong Ik; Kang, SukJae Joshua; Lim, Chae-Seok; Sim, Su-Eon; Shim, Jaehoon; Kim, Ji-Il; Kim, Siyong; Choi, Tae-Hyeok; Ye, Sanghyun; Lee, Jaehyun; Park, Pojeong; Kim, Somi; Do, Jeehaeh; Park, Jihye; Islam, Md Ariful; Kim, Hyun Jeong; Turck, Christoph W; Collingridge, Graham L; Zhuo, Min; Kaang, Bong-Kiun

    2018-01-16

    Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Altered interface adhesion molecules in oral lichen planus.

    Science.gov (United States)

    Ramirez-Amador, V; Dekker, N P; Lozada-Nur, F; Mirowski, G W; MacPhail, L A; Regezi, J A

    1996-09-01

    To evaluate expression of key epithelial-connective tissue interface adhesion molecules (basal keratinocyte integrins and extracellular matrix receptors) in oral lichen planus (LP). Integrins alpha 3, alpha 6, beta 1, beta 4 and basement membrane proteins laminin 1, laminin 5, collagen IV, and collagen VII were immunohistochemically identified in frozen biopsy specimens (14 oral LP and II matched controls) using a standard avidin-biotin-peroxidase technique. An increased staining intensity of all antigens in LP was shown, as compared to controls. Integrin expression by LP keratinocytes was generally more intense and appeared on more upper level cells. Staining for basement membrane-associated extracellular matrix proteins was also generally more intense, although fragmentation and gaps were typically seen. Reactions for alpha 6, beta 4, laminin 5, and collagen VII stains were particularly intense along the basement membrane. In LP, strands of laminin 5, collagen IV, and collagen VII appeared in the submucosa approximating or duplicating the basement membrane. The apparent increased expression of the interface-associated adhesion molecules may be reflective of a keratinocyte compensatory response (due to lymphocyte-mediated damage) that would functionally help resist epithelial separation (ulceration). Expression of alpha 3 beta 1 and alpha 6 beta 4 would also assist in epithelial migration associated with wound repair. We interpret the submucosal extensions and deposits of basement membrane proteins as representing remnants of basement membrane, indicating recent remodeling or atrophy of epithelial rete ridges.

  7. Cleavage and Cell Adhesion Properties of Human Epithelial Cell Adhesion Molecule (HEPCAM)*

    Science.gov (United States)

    Tsaktanis, Thanos; Kremling, Heidi; Pavšič, Miha; von Stackelberg, Ricarda; Mack, Brigitte; Fukumori, Akio; Steiner, Harald; Vielmuth, Franziska; Spindler, Volker; Huang, Zhe; Jakubowski, Jasmine; Stoecklein, Nikolas H.; Luxenburger, Elke; Lauber, Kirsten; Lenarčič, Brigita; Gires, Olivier

    2015-01-01

    Human epithelial cell adhesion molecule (HEPCAM) is a tumor-associated antigen frequently expressed in carcinomas, which promotes proliferation after regulated intramembrane proteolysis. Here, we describe extracellular shedding of HEPCAM at two α-sites through a disintegrin and metalloprotease (ADAM) and at one β-site through BACE1. Transmembrane cleavage by γ-secretase occurs at three γ-sites to generate extracellular Aβ-like fragments and at two ϵ-sites to release human EPCAM intracellular domain HEPICD, which is efficiently degraded by the proteasome. Mapping of cleavage sites onto three-dimensional structures of HEPEX cis-dimer predicted conditional availability of α- and β-sites. Endocytosis of HEPCAM warrants acidification in cytoplasmic vesicles to dissociate protein cis-dimers required for cleavage by BACE1 at low pH values. Intramembrane cleavage sites are accessible and not part of the structurally important transmembrane helix dimer crossing region. Surprisingly, neither chemical inhibition of cleavage nor cellular knock-out of HEPCAM using CRISPR-Cas9 technology impacted the adhesion of carcinoma cell lines. Hence, a direct function of HEPCAM as an adhesion molecule in carcinoma cells is not supported and appears to be questionable. PMID:26292218

  8. 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

    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......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...

  9. 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...

  10. Relationship between Leukopenia and Intercellular Adhesion Molecules in Graves' Disease

    Science.gov (United States)

    Gao, Y; Shen, HJ; Zhou, P; Hu, H; Tang, JL; Peng, LL; Tong, J

    2014-01-01

    ABSTRACT Objective: Changes in soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin levels as well as leukocyte count were examined in this study to explore the relationship between leukopenia and ICAMs in Graves' disease (GD). Methods: Fasting blood samples were obtained from 37 GD patients with normal leukocytes and 32 GD patients with leukopenia. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum sICAM-1 and E-selectin levels for comparison. The same analyses were repeated for the GD patients with leukopenia after glucocorticoid treatment (15 mg/day to 30 mg/day prednisone). Results: The ELISA results showed that E-selectin levels were higher in GD patients with leukopenia than those with normal leukocytes (p leukopenia, and glucocorticoids (prednisone) could decrease E-selectin level, which may be a new therapy target for GD with leukopenia. PMID:25803374

  11. 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.

  12. Adhesion Molecule Expression in Human Endothelial Cells under Simulated Microgravity

    Science.gov (United States)

    Rudimov, E. G.; Andreeva, E. R.; Buravkova, L. B.

    2013-02-01

    High gravisensitivity of endothelium is now well recognized. Therefore, the microgravity can be one of the main factors affecting the endothelium in space flight. In this work we studied the effects of gravity vector randomization (3D-clinorotation in RPM) on the viability of endothelial cells from human umbilical vein (HUVEC) and the expression of adhesion molecules on its surface. After RPM exposure, HUVEC conditioning medium was collected for cytokines evaluation, a part of vials was used for immunocytochemistry and other one - for cytofluorimetric analysis of ICAM-I, VCAM-I, PECAM-I, E-selectin, Endoglin, VE-cadherin expression. The viability of HUVEC and constitutive expression of EC marker molecules PECAM-I and Endoglin were similar in all experimental groups both after 6 and 24 hrs of exposure. There were no differences in ICAM-I and E-selectin expression on HUVEC in 3 groups after 6 hrs of exposure. 24 hrs incubation has provoked decrease in ICAM-I and E-selectin expression. Thus, gravity vector randomization can lead to the disruption of ECs monolayer.

  13. 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

  14. Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1

    NARCIS (Netherlands)

    Rathjen, Thomas; Yan, Xin; Kononenko, Natalia L.; Ku, Min-Chi; Song, Kun; Ferrarese, Leiron; Tarallo, Valentina; Puchkov, Dmytro; Kochlamazashvili, Gaga; Brachs, Sebastian; Varela, Luis; Szigeti-Buck, Klara; Yi, Chun-Xia; Schriever, Sonja C.; Tattikota, Sudhir Gopal; Carlo, Anne Sophie; Moroni, Mirko; Siemens, Jan; Heuser, Arnd; van der Weyden, Louise; Birkenfeld, Andreas L.; Niendorf, Thoralf; Poulet, James F. A.; Horvath, Tamas L.; Tschöp, Matthias H.; Heinig, Matthias; Trajkovski, Mirko; Haucke, Volker; Poy, Matthew N.

    2017-01-01

    Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2

  15. The novel carbohydrate epitope L3 is shared by some neural cell adhesion molecules.

    Science.gov (United States)

    Kücherer, A; Faissner, A; Schachner, M

    1987-06-01

    The monoclonal L3 antibody reacts with an N-glycosidically linked carbohydrate structure on at least nine glycoproteins of adult mouse brain. Three out of the L3 epitope-carrying glycoproteins could be identified as the neural cell adhesion molecules L1 and myelin-associated glycoprotein, and the novel adhesion molecule on glia. Expression of the L3 carbohydrate epitope is regulated independently of the protein backbone of these three glycoproteins. Based on the observation that out of three functionally characterized L3 epitope-carrying glycoproteins three fulfill the operational definition of an adhesion molecule, we would like to suggest that they form a new family of adhesion molecules that is distinct from the L2/HNK-1 carbohydrate epitope family of neural cell adhesion molecules. Interestingly, some members in each family appear to be unique to one family while other members belong to the two families.

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

    DEFF Research Database (Denmark)

    Møller, C J; Christgau, S; Williamson, M R

    1992-01-01

    (delta-cells), and pancreatic polypeptide (PP-cells) in a sequential order. The endocrine cells are believed to arise from a stem cell with neuronal traits. The developmental lineage from a common neuron-like progenitor is evidenced by: transient coexpression of more than one cell type-specific hormone......-cadherin in brain. Insulinoma cells express E-cadherin but differ from primary islet cells by expressing a second cadherin molecule, which is similar to N-cadherin. The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype......The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin...

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

    Science.gov (United States)

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

    2016-09-01

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

  18. Purification, composition, and structure of macrophage adhesion molecule

    International Nuclear Information System (INIS)

    Remold-O'Donnell, E.; Savage, B.

    1988-01-01

    Macrophage adhesion molecule (MAM) is a surface heterodimer consisting of the trypsin- and plasmin-sensitive glycopeptide gp160 (MAM-α) and the glycopeptide gp93 (MAM-β). MAM, which is the guinea pig analog of Mo1 and Mac-1, was purified from detergent lysates of peritoneal neutrophils by lentil lectin chromatography and M2-antibody chromatography. The pure heterodimer molecule was dissociated by acidic conditions (pH 3.5), and MAM-α and MAM-β were separated by M7-antibody chromatography. MAM-β is an ∼ 640 amino acid residue polypeptide with exceptionally high cysteine content. At 7.2 residues per 100 amino acids, Cys/2 of MAM-β is more than 3 times the mean for 200 purified proteins. Reactivity with six β-subunit-specific 125 I-labeled monoclonal antibodies recognizing at least four epitopes demonstrated that intrapeptide disulfide bonds are required to maintain the structure of MAM-β. All six antibodies failed to react when MAM-β was treated with reducing agents. MAM-β is 18% carbohydrate; the major monosaccharides are mannose, N-acetylglucosamine, galactose, and sialic acid. MAM-β is estimated to contain five to six N-linked carbohydrate units. MAM-α is an ∼ 1100-residue polypeptide with lower Cys/2 content (2.0 residues per 100 amino acid residues). MAM-α is 21% carbohydrate. The major monosaccharides are mannose, N-acetylglucosamine, galactose, and sialic acid; the mannose content is higher in MAM-α than MAM-β is estimated to contain 12 N-linked carbohydrate units

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  20. PSA-NCAM-Negative Neural Crest Cells Emerging during Neural Induction of Pluripotent Stem Cells Cause Mesodermal Tumors and Unwanted Grafts

    Science.gov (United States)

    Lee, Dongjin R.; Yoo, Jeong-Eun; Lee, Jae Souk; Park, Sanghyun; Lee, Junwon; Park, Chul-Yong; Ji, Eunhyun; Kim, Han-Soo; Hwang, Dong-Youn; Kim, Dae-Sung; Kim, Dong-Wook

    2015-01-01

    Summary Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)− cells among the early NPCs caused tumors, whereas PSA-NCAM+ cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM− cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM− cells in a gradient manner mixed with PSA-NCAM+ cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN+ cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM− cells eliminates the tumorigenic potential originating from NCSCs after transplantation. PMID:25937368

  1. Research on effects of ionizing radiation of human peripheral blood white cell adhesive molecules

    International Nuclear Information System (INIS)

    Li Haijun; Cheng Ying; Le Chen; Min Rui

    2008-01-01

    Objective: To investigate the links between expression and function of adhesive molecule on the surface of irradiated peripheral blood white cells. Methods: Heparinized human peripheral blood was exposed to γ rays with different dose. At the different post-radiation time adhesive molecule expression on cellular surface was determined by double fluorescence labeling antibodies which were against adhesive molecule and special mark of granulocyte or mononuclear cell respectively with flow cytometry, and cellular adhesive ability to different matrixes mediated by adhesive molecule was estimated by commercializing enzyme-linked immunosorbent assay kit and crystalviolet dying. Results: A decline pattern of CD11b on surface of mononuclear cells and CD29 on surface of granulocyte with irradiation dose increase was found. The changes of adhesive ability of mononuclear cells to substance of β1-integrin and collagen-I was well related with irradiation dose. Conclusion: Good relationship shown by the changes of adhesive molecule expression and adhesive ability mediated by the molecules on the surface of peripheral blood white cells with radiation dose was primary base of further research on indicting exposure dose by biomarker. (authors)

  2. Characterisation of genetic variation in ST8SIA2 and its interaction region in NCAM1 in patients with bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Alex D Shaw

    Full Text Available Alpha-2,8-sialyltransferase 2 (ST8SIA2 is an enzyme responsible for the transfer of polysialic acid (PSA to glycoproteins, principally the neuronal cell adhesion molecule (NCAM1, and is involved in neuronal plasticity. Variants within ST8SIA2 have previously shown association with bipolar disorder, schizophrenia and autism. In addition, altered PSA-NCAM expression in brains of patients with schizophrenia or bipolar disorder indicates a functional dysregulation of glycosylation in mental illness. To explore the role of sequence variation affecting PSA-NCAM formation, we conducted a targeted re-sequencing study of a ∼ 100 kb region--including the entire ST8SIA2 gene and its region of interaction with NCAM1--in 48 Caucasian cases with bipolar disorder using the Roche 454 platform. We identified over 400 DNA variants, including 47 putative novel variants not described in dbSNP. Validation of a subset of variants via Sequenom showed high reliability of Roche 454 genotype calls (97% genotype concordance, with 80% of novel variants independently verified. We did not observe major loss-of-function mutations that would affect PSA-NCAM formation, either by ablating ST8SIA2 function or by affecting the ability of NCAM1 to be glycosylated. However, we identified 13 SNPs in the UTRs of ST8SIA2, a synonymous coding SNP in exon 5 (rs2305561, P207P and many additional non-coding variants that may influence splicing or regulation of ST8SIA2 expression. We calculated nucleotide diversity within ST8SIA2 on specific haplotypes, finding that the diversity on the specific "risk" and "protective" haplotypes was lower than other non-disease-associated haplotypes, suggesting that putative functional variation may have arisen on a spectrum of haplotypes. We have identified common and novel variants (rs11074064, rs722645, 15:92961050 that exist on a spectrum of haplotypes, yet are plausible candidates for conferring the effect of risk and protective haplotypes via

  3. Targeting cellular adhesion molecules, chemokines and chemokine receptors in rheumatoid arthritis

    NARCIS (Netherlands)

    Haringman, Jasper J.; Oostendorp, Roos L.; Tak, Paul P.

    2005-01-01

    The development of specific targeted therapies, such as anti-TNF-alpha treatment, for chronic inflammatory disorders such as rheumatoid arthritis, has significantly improved treatment, although not all patients respond. Targeting cellular adhesion molecules and chemokines/chemokine receptors as

  4. Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

    International Nuclear Information System (INIS)

    Plevova, P.

    2002-01-01

    Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

  5. Interleukin-6 but not soluble adhesion molecules has short-term ...

    African Journals Online (AJOL)

    Interleukin-6 but not soluble adhesion molecules has short-term prognostic value on mortality in patients with acute ST-segment elevation myocardial infarction. ZX Fan, Q Hua, J Tan, J Gao, RK Liu, Z Yang ...

  6. Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration

    Science.gov (United States)

    Sumagin, Ronen; Parkos, Charles A

    2014-01-01

    Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from the surrounding tissue. Others serve as docking structures for invading viruses and bacteria, while also regulating the immune response. They can either obstruct or serve as footholds for the immune cells recruited to mucosal surfaces. Currently, it is well appreciated that adhesion molecules collectively serve as environmental cue sensors and trigger signaling events to regulate epithelial function through their association with the cell cytoskeleton and various intracellular adapter proteins. Immune cells, particularly neutrophils (PMN) during transepithelial migration (TEM), can modulate adhesion molecule expression, conformation, and distribution, significantly impacting epithelial function and tissue homeostasis. This review discusses the roles of key intestinal epithelial adhesion molecules in regulating PMN trafficking and outlines the potential consequences on epithelial function. PMID:25838976

  7. Modulation of lens cell adhesion molecules by particle beams

    Science.gov (United States)

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

    2001-01-01

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

  8. Vascular Cell Adhesion Molecule 1, Intercellular Adhesion Molecule 1, and Cluster of Differentiation 146 Levels in Patients with Type 2 Diabetes with Complications.

    Science.gov (United States)

    Hocaoglu-Emre, F Sinem; Saribal, Devrim; Yenmis, Guven; Guvenen, Guvenc

    2017-03-01

    Type 2 diabetes mellitus (T2DM) is a multisystemic, chronic disease accompanied by microvascular complications involving various complicated mechanisms. Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and cluster of differentiation-146 (CD146) are mainly expressed by endothelial cells, and facilitate the adhesion and transmigration of immune cells, leading to inflammation. In the present study, we evaluated the levels of soluble adhesion molecules in patients with microvascular complications of T2DM. Serum and whole blood samples were collected from 58 T2DM patients with microvascular complications and 20 age-matched healthy subjects. Levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) were assessed using enzyme-linked immunosorbent assay, while flow cytometry was used to determine CD146 levels. Serum sICAM-1 levels were lower in T2DM patients with microvascular complications than in healthy controls (Pmolecule levels were not correlated with the complication type. In the study group, most of the patients were on insulin therapy (76%), and 95% of them were receiving angiotensin-converting enzyme (ACE)-inhibitor agents. Insulin and ACE-inhibitors have been shown to decrease soluble adhesion molecule levels via various mechanisms, so we suggest that the decreased or unchanged levels of soluble forms of cellular adhesion molecules in our study group may have resulted from insulin and ACE-inhibitor therapy, as well as tissue-localized inflammation in patients with T2DM. Copyright © 2017 Korean Endocrine Society

  9. Circulating cellular adhesion molecules and risk of diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA).

    Science.gov (United States)

    Pankow, J S; Decker, P A; Berardi, C; Hanson, N Q; Sale, M; Tang, W; Kanaya, A M; Larson, N B; Tsai, M Y; Wassel, C L; Bielinski, S J

    2016-07-01

    To test the hypothesis that soluble cellular adhesion molecules would be positively and independently associated with risk of diabetes. Soluble levels of six cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1, E-cadherin, L-selectin and P-selectin) were measured in participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study. Participants were then followed for up to 10 years to ascertain incident diabetes. Sample sizes ranged from 826 to 2185. After adjusting for age, sex, race/ethnicity, BMI and fasting glucose or HbA1c , four cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1 and E-cadherin) were positively associated with incident diabetes and there was a statistically significant trend across quartiles. Comparing the incidence of diabetes in the highest and lowest quartiles of each cellular adhesion molecule, the magnitude of association was largest for E-selectin (hazard ratio 2.49; 95% CI 1.26-4.93) and ICAM-1 (hazard ratio 1.76; 95% CI 1.22-2.55) in fully adjusted models. Tests of effect modification by racial/ethnic group and sex were not statistically significant for any of the cellular adhesion molecules (P > 0.05). The finding of significant associations between multiple cellular adhesion molecules and incident diabetes may lend further support to the hypothesis that microvascular endothelial dysfunction contributes to risk of diabetes. © 2016 Diabetes UK.

  10. The relation between oxidative stress and adhesion molecules in ...

    African Journals Online (AJOL)

    Background: Antioxidant potential decreases while plasma lipid peroxidation products increase in type1 diabetes mellitus. The vascular endothelium is a major target of oxidative stress (OS). Reactive oxygen species signal events leading to impairment of endothelial function and promotion of leukocyte adhesion to the ...

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

    DEFF Research Database (Denmark)

    Jensen, Jakob; Krakauer, Martin; Sellebjerg, Finn

    2005-01-01

    inconsistent. We found decreases in CD4 and CD8 T cell expression of the CD49d/VLA-4 molecule, increases in plasma concentrations of soluble vascular cell adhesion molecule (sVCAM-1), and increases in plasma concentrations of tumor necrosis factor and interleukin (IL)-12 p40 chain in patients with MS who were...

  12. 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.

  13. Prediction of residual valvular lesions in rheumatic heart disease: role of adhesion molecules.

    Science.gov (United States)

    Hafez, Mona; Yahia, Sohier; Eldars, Waleed; Eldegla, Heba; Matter, Mohamed; Attia, Gehan; Hawas, Samia

    2013-03-01

    Rheumatic heart disease (RHD) is a chronic condition characterized by fibrosis and scarring of the cardiac valves and damage to the heart muscle, leading to congestive heart failure and death. This prospective cohort study was conducted to investigate the possible relation between the levels of serum adhesion molecules and acute rheumatic fever (ARF) carditis, valvular insult severity, and residual valvular lesion after improvement of rheumatic activity. Serum levels of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were assayed by enzyme-linked immunoassay (ELISA) for 50 children with ARF carditis during activity and after improvement and for 50 healthy children as control subjects. After the acute attack, patients were followed up regularly to detect residual valvular lesion. The serum levels of these adhesion molecules were significantly higher in the patients than in the control group (p valvular lesion (ICAM-1, >1,032.3 μg/ml; VCAM-1, >3,662.3 μg/ml; E-selectin, >104.8 μg/ml). Finally, by combining the three adhesion molecules in a single prediction model, the highest area under the curve (AUC) ± standard error (SE) was obtained (0.869 ± 0.052), and the positive likelihood ratio for having a residual valvular lesion was increased (17.33). Levels of serum adhesion molecules could predict residual valvular lesions in RHD patients. The authors recommend that the serum level of adhesion molecules be measured in all cases of ARF carditis.

  14. 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.

  15. Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis

    Directory of Open Access Journals (Sweden)

    Guirado Ramon

    2012-01-01

    Full Text Available Abstract Background Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents. Results We have analyzed the effects of 14 days of fluoxetine treatment on the density of puncta expressing PSA-NCAM and different presynaptic markers in the medial prefrontal cortex, hippocampus and amygdala of middle-aged (8 months old rats. The density of puncta expressing PSA-NCAM increased in the dorsal cingulate cortex, as well as in different hippocampal and amygdaloid regions. In these later regions there were also increases in the density of puncta expressing glutamic acid decarboxylase 65/67 (GAD6, synaptophysin (SYN, PSA-NCAM/SYN and PSA-NCAM/GAD6, but a decrease of those expressing vesicular glutamate transporter 1 (VGluT1. Since there is controversy on the effects of antidepressants on neurogenesis during aging, we analyzed the number of proliferating cells expressing Ki67 and that of immature neurons expressing doublecortin or PSA-NCAM. No significant changes were found in the subgranular zone, but the number of proliferating cells decreased in the subventricular zone. Conclusions These results indicate that the effects of fluoxetine in middle-aged rats are different to those previously described in young-adult animals, being more restricted in the mPFC and even following an opposite direction in the amygdala or the subventricular zone.

  16. Postprandial lipaemia and endothelial adhesion molecules in pre- and postmenopausal Spanish women.

    Science.gov (United States)

    Schoppen, S; Pérez-Granados, A M; Navas-Carretero, S; Vaquero, M P

    2010-01-01

    Postprandial hyperlipaemia is an independent risk factor for atherosclerosis. To compare postprandial lipaemia and fasting adhesion molecules levels in healthy young premenopausal(PrW) and postmenopausal (PoW) Spanish women. Twenty healthy PrW and 18 healthy PoW participated in a postprandial 7-hour intervention study. All participants were given a fat-rich standard meal (11.8% saturated, 39.7% monounsaturated, and 6.6% polyunsaturated) after a 12 h fast. Blood samples were taken at baseline and at 60, 120, 240, 360 and 420 min after eating. Triacylglycerols (TAG), total cholesterol (Chol), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1) were determined in fasting serum samples and TAG and total Chol postprandial levels were measured. Anthropometric data, serum lipid and sICAM-1 presented significant higher values in PoW compared to PrW, but sVCAM-1 did not significantly differ between groups. Postprandial TAG and Chol concentrations in PoW were significantly higher than in PrW (p postprandial response to a fat rich meal and soluble intercellular adhesion molecules concentrations indicate a higher cardiovascular risk pattern in postmenopausal compared to premenopausal women. Soluble vascular adhesion molecule levels seem to be influenced not only by age and menopause, but also other factors like usual diet.

  17. Small Interfering RNA Efficiently Suppresses Adhesion Molecule Expression on Pulmonary Microvascular Endothelium

    Directory of Open Access Journals (Sweden)

    Tobias Walker

    2011-01-01

    Full Text Available Background. Adhesion molecules are known to influence postoperative organ function, they are hardly involved in the inflammatory response following the ischemia-reperfusion injury. We sought to investigate the potency of small interfering RNAs to suppress adhesion molecule expression in human pulmonary microvascular endothelial cells. Methods. Human lung microvascular endothelial cells were transfected with specific siRNA followed by a stimulation of the cells with an inflammatory cytokine. Adhesion molecule expression was determined by FACS-analysis, and reduction of intracellular mRNA was determined by qRT-PCR. Furthermore, the attachment of isolated neutrophils on the endothelial layer was determined after siRNA transfection. Results. In summary, siRNA transfection significantly decreased the percentage positive cells in a single cocktail transfection of each adhesion molecule investigated. Adhering neutrophils were diminished as well. Conclusion. siRNA might be a promising tool for the effective suppression of adhesion molecule expression on pulmonary microvascular cells, potentially minimizing leukocyte-endothelial depending interactions of a pulmonary allograft.

  18. Adhesion molecules expression in CLL: Potential impact on clinical and hematological parameters.

    Science.gov (United States)

    Kamel, Azza M; El-Sharkawy, Nahla M; Osman, Randa A; Abd El-Fattah, Eman K; El-Noshokaty, Essam; Abd El-Hamid, Thoraya; Kandeel, Eman Z

    2016-03-01

    B-cell chronic lymphocytic leukemia (CLL) is marked by the accumulation of CD5+ B lymphocytes within the blood, bone marrow (BM), and secondary lymphoid tissues. Abnormalities in the expression and function of cell adhesion molecules may account for the patterns of intra-nodal growth and hematogenous spread of the malignant cells. Chemokines and integrin-mediated adhesion and trans-endothelial migration (TEM) are central aspects in trafficking and retention of hematopoietic cells in the BM and lymphoid organs. This work was conducted to study adhesion molecules status in CLL and its potential impact on both hematological and clinical parameters. The study included 78 newly diagnosed CLL patients. Immunophenotyping was performed on peripheral blood using the chronic lymphoid panel. Adhesion molecules (CD11a, CD11b, CD49d, CD49C, CD29 and CD38) were tested using monoclonal antibodies and analyzed by Flow Cytometry. Positive correlation was encountered between adhesion molecules: CD38 with CD49d (r=0.25, p=0.028), CD11a with CD11b, CD49d and CD29 (r=0.394, p=0.001; r=0.441, p=molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  19. Oxidized low-density lipoprotein-induced microparticles promote endothelial monocyte adhesion via intercellular adhesion molecule 1.

    Science.gov (United States)

    Fu, Zhiwei; Zhou, Enchen; Wang, Xu; Tian, Mingda; Kong, Jian; Li, Jizhao; Ji, Liang; Niu, Chenguang; Shen, Haitao; Dong, Shuying; Liu, Changjie; Vermorken, Alphons; Willard, Belinda; Zu, Lingyun; Zheng, Lemin

    2017-11-01

    Oxidized low-density lipoprotein (oxLDL) accumulates early in atherosclerotic lesions and plays an important role in the progressive formation of atherosclerotic plaques. Endothelial derived microparticles (EMPs) form a heterogeneous population of microparticle release and the subsequent regulation of the endothelial activation. EMPs were collected from the medium of human umbilical vein endothelial cells (HUVECs) treated with oxLDL or PBS as control. We find that oxLDL increases the release of EMPs containing intercellular adhesion molecule 1 (ICAM-1) but not vascular cell adhesion molecule 1 (VCAM-1). Confocal microscopy analysis further demonstrates that these EMPs interact with endothelial cells and increase the expression of ICAM-1 in HUVECs. The fact that injecting oxLDL-induced EMPs via the tail vein of ICR mice augments ICAM-1 expression on aortic endothelial cells confirms our results in vivo. Finally, oxLDL-induced EMPs from HUVECs increase the adhesion of monocytes to endothelial cells as determined by the adhesion assay. Our study suggests that oxLDL may augment the release of EMPs harboring increased levels of ICAM-1 that can be transferred to endothelial cells elsewhere. This leads to increased monocyte recruitment in other regions where oxLDL accumulation was initially more limited. EMPs may therefore serve as the mediator that propagates oxLDL-induced endothelial inflammation. Copyright © 2017 the American Physiological Society.

  20. An Evolutionary-Conserved Function of Mammalian Notch Family Members as Cell Adhesion Molecules

    Science.gov (United States)

    Murata, Akihiko; Yoshino, Miya; Hikosaka, Mari; Okuyama, Kazuki; Zhou, Lan; Sakano, Seiji; Yagita, Hideo; Hayashi, Shin-Ichi

    2014-01-01

    Notch family members were first identified as cell adhesion molecules by cell aggregation assays in Drosophila studies. However, they are generally recognized as signaling molecules, and it was unclear if their adhesion function was restricted to Drosophila. We previously demonstrated that a mouse Notch ligand, Delta-like 1 (Dll1) functioned as a cell adhesion molecule. We here investigated whether this adhesion function was conserved in the diversified mammalian Notch ligands consisted of two families, Delta-like (Dll1, Dll3 and Dll4) and Jagged (Jag1 and Jag2). The forced expression of mouse Dll1, Dll4, Jag1, and Jag2, but not Dll3, on stromal cells induced the rapid and enhanced adhesion of cultured mast cells (MCs). This was attributed to the binding of Notch1 and Notch2 on MCs to each Notch ligand on the stromal cells themselves, and not the activation of Notch signaling. Notch receptor-ligand binding strongly supported the tethering of MCs to stromal cells, the first step of cell adhesion. However, the Jag2-mediated adhesion of MCs was weaker and unlike other ligands appeared to require additional factor(s) in addition to the receptor-ligand binding. Taken together, these results demonstrated that the function of cell adhesion was conserved in mammalian as well as Drosophila Notch family members. Since Notch receptor-ligand interaction plays important roles in a broad spectrum of biological processes ranging from embryogenesis to disorders, our finding will provide a new perspective on these issues from the aspect of cell adhesion. PMID:25255288

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

    Directory of Open Access Journals (Sweden)

    Y. P. Kovalchuk

    2015-09-01

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

  2. The Drosophila cell adhesion molecule Neuroglian regulates Lissencephaly-1 localisation in circulating immunosurveillance cells

    Directory of Open Access Journals (Sweden)

    Williams Michael J

    2009-03-01

    Full Text Available Abstract Background When the parasitoid wasp Leptopilina boulardi lays its eggs in Drosophila larvae phagocytic cells called plasmatocytes and specialized cells known as lamellocytes encapsulate the egg. This requires these circulating immunosurveillance cells (haemocytes to change from a non-adhesive to an adhesive state enabling them to bind to the invader. Interestingly, attachment of leukocytes, platelets, and insect haemocytes requires the same adhesion complexes as epithelial and neuronal cells. Results Here evidence is presented showing that the Drosophila L1-type cell adhesion molecule Neuroglian (Nrg is required for haemocytes to encapsulate L. boulardi wasp eggs. The amino acid sequence FIGQY containing a conserved phosphorylated tyrosine is found in the intracellular domain of all L1-type cell adhesion molecules. This conserved tyrosine is phosphorylated at the cell periphery of plasmatocytes and lamellocytes prior to parasitisation, but dephosphorylated after immune activation. Intriguingly, another pool of Nrg located near the nucleus of plasmatocytes remains phosphorylated after parasitisation. In mammalian neuronal cells phosphorylated neurofascin, another L1-type cell adhesion molecule interacts with a nucleokinesis complex containing the microtubule binding protein lissencephaly-1 (Lis1 1. Interestingly in plasmatocytes from Nrg mutants the nucleokinesis regulating protein Lissencephaly-1 (Lis1 fails to localise properly around the nucleus and is instead found diffuse throughout the cytoplasm and at unidentified perinuclear structures. After attaching to the wasp egg control plasmatocytes extend filopodia laterally from their cell periphery; as well as extending lateral filopodia plasmatocytes from Nrg mutants also extend many filopodia from their apical surface. Conclusion The Drosophila cellular adhesion molecule Neuroglian is expressed in haemocytes and its activity is required for the encapsulation of L. boularli eggs. At

  3. Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2011-01-01

    Full Text Available Leukocyte adhesion to the vascular endothelium and subsequent transendothelial migration play essential roles in the pathogenesis of cardiovascular diseases such as atherosclerosis. The leukocyte adhesion is mediated by localized activation of the endothelium through the action of inflammatory cytokines. The exact proinflammatory factors, however, that activate the endothelium and their cellular sources remain incompletely defined.Using bone marrow-derived mast cells from wild-type, Tnf(-/-, Ifng(-/-, Il6(-/- mice, we demonstrated that all three of these pro-inflammatory cytokines from mast cells induced the expression of vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1, P-selectin, and E-selectin in murine heart endothelial cells (MHEC at both mRNA and protein levels. Compared with TNF-α and IL6, IFN-γ appeared weaker in the induction of the mRNA levels, but at protein levels, both IL6 and IFN-γ were weaker inducers than TNF-α. Under physiological shear flow conditions, mast cell-derived TNF-α and IL6 were more potent than IFN-γ in activating MHEC and in promoting neutrophil adhesion. Similar observations were made when neutrophils or macrophages were used. Neutrophils and macrophages produced the same sets of pro-inflammatory cytokines as did mast cells to induce MHEC adhesion molecule expression, with the exception that macrophage-derived IFN-γ showed negligible effect in inducing VCAM-1 expression in MHEC.Mast cells, neutrophils, and macrophages release pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL6 that induce expression of adhesion molecules in endothelium and recruit of leukocytes, which is essential to the pathogenesis of vascular inflammatory diseases.

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

    Directory of Open Access Journals (Sweden)

    Aliyev Emil

    2004-04-01

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

  5. 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

    -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 ... was associated with increased expression of the adhesion molecule CD11a/CD18 on lymphocytes, while the expression of activation molecules on lymphocytes was unchanged....

  6. A novel attribute of enoxaparin: inhibition of monocyte adhesion to endothelial cells by a mechanism involving cell adhesion molecules.

    Science.gov (United States)

    Manduteanu, I; Voinea, M; Capraru, M; Dragomir, E; Simionescu, M

    2002-05-01

    Enoxaparin is a low molecular weight heparin, widely accepted as anticoagulant or antithrombotic drug, and is likely to have a role in acute inflammation. To evaluate the anti-inflammatory potential of enoxaparin, we investigated the direct effect of the drug on the activation of endothelial cells. For this purpose we set up an in vitro system in which cultured valvular endothelial cells (VEC) activated by tumor necrosis factor alpha or lipopolysaccharide were exposed to a monocytic cell line; these conditions induced a significant adhesion of monocytes to VEC. Adhesion assays, ELISA, and flow cytometric analysis revealed that pretreatment with enoxaparin, at a relevant plasma concentration (16 microg/ml), acts upon activation of VEC by inhibition of lipopolysaccharide-induced E-selectin expression and tumor necrosis factor stimulated ICAM-1 expression, thus reducing monocyte adhesion to VEC. These results suggest a novel function of enoxaparin, namely to protect VEC from activation and inhibiting the expression of cell adhesion molecules. Copyright 2002 S. Karger AG, Basel

  7. Curcumin attenuates TNF-α-induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and proinflammatory cytokines in human endometriotic stromal cells.

    Science.gov (United States)

    Kim, Ki-Hyung; Lee, Eun Na; Park, Jin Kyeong; Lee, Ja-Rang; Kim, Ji-Hyun; Choi, Hak-Jong; Kim, Bong-Seon; Lee, Hee-Woo; Lee, Kyu-Sup; Yoon, Sik

    2012-07-01

    Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has long been used in folk medicine as an antiinflammatory remedy in Asian countries. Endometriosis is a chronic gynecological inflammatory disorder in which immune system deregulation may play a role in its initiation and progression. A number of mediators, including cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); proinflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6 and IL-8; and chemokines such as monocyte chemotactic protein-1 (MCP-1), play key roles in the pathogenesis of endometriosis. The aim of our study was to explore the effect of curcumin on the expression of these critical molecules in human ectopic endometriotic stromal cells isolated from women with endometriosis. Endometriotic stromal cells treated with curcumin showed marked suppression of TNF-α-induced mRNA expression of ICAM-1 and VCAM-1. Curcumin treatment also significantly decreased the TNF-α-induced cell surface and total protein expression of ICAM-1 and VCAM-1 in a dose-dependent manner. In addition, treatment of endometriotic stromal cells with curcumin markedly inhibited TNF-α-induced secretion of IL-6, IL-8 and MCP-1. Furthermore, curcumin inhibited the activation of transcription factor NF-κB, a key regulator of inflammation, in human endometriotic stromal cells. These findings suggest that curcumin may have potential therapeutic uses in the prevention and treatment of endometriosis. Copyright © 2011 John Wiley & Sons, Ltd.

  8. The association between soluble intercellular adhesion molecule-1 levels in drained dialysate and peritoneal injury in peritoneal dialysis.

    Science.gov (United States)

    Igarashi, Yusuke; Morishita, Yoshiyuki; Yoshizawa, Hiromichi; Imai, Reika; Imai, Toshimi; Hirahara, Ichiro; Akimoto, Tetsu; Ookawara, Susumu; Ishibashi, Kenichi; Muto, Shigeaki; Nagata, Daisuke

    2017-11-01

    Chronic inflammation of the peritoneum causes peritoneal injury in patients on peritoneal dialysis. Intercellular adhesion molecule-1 and its circulating form, soluble intercellular adhesion molecule-1, play pivotal roles in inflammation. However, their role in peritoneal injury is unclear. We measured changes in intercellular adhesion molecule-1 expression in the peritoneum of a peritoneal injury model in rats. The associations between soluble intercellular adhesion molecule-1 levels in drained dialysate and the solute transport rate (D/P-Cr and D/D0-glucose) determined by the peritoneal equilibration test, and matrix metalloproteinase-2 levels in drained dialysate were investigated in 94 peritoneal drained dialysate samples. Intercellular adhesion molecule-1 expression was increased in the peritoneum of rats with peritoneal injury. Soluble intercellular adhesion molecule-1 levels in drained dialysate were significantly positively correlated with D/P-Cr (r = .51, p molecule-1expression is increased in the peritoneum of a peritoneal injury model in the rat, and soluble intercellular adhesion molecule-1 levels in drained dialysate are associated with peritoneal injury in patients on peritoneal dialysis. These results suggest that soluble intercellular adhesion molecule-1 could be a novel biomarker of peritoneal injury in patients on peritoneal dialysis.

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

    Science.gov (United States)

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

    2016-04-13

    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 abundantly expressed in the adult renal (Malpighian) tubule rather than in neuronal tissues. The role Fas2 serves in this epithelium is unknown. Here we show that Fas2 is essential to brush border maintenance in renal tubules of Drosophila. Fas2 is dynamically expressed during tubule morphogenesis, localizing to the brush border whenever the tissue is transport competent. Genetic manipulations of Fas2 expression levels impact on both microvilli length and organization, which in turn dramatically affect stimulated rates of fluid secretion by the tissue. Consequently, we demonstrate a radically different role for this well-known cell adhesion molecule, and propose that Fas2-mediated intermicrovillar homophilic adhesion complexes help stabilize the brush border.

  10. 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...... cell activation. While it was originally believed that ICAM-1 played a purely adhesive role, recent evidence suggests that it can itself transduce biochemical signals. We demonstrate that cross-linking of ICAM-1 results in the up-regulation of class II major histocompatibility complex, and we...... investigate the biochemical mechanism for the signaling role of ICAM-1. We show that cross-linking of ICAM-1 on the B lymphoma line A20 induces an increase in tyrosine phosphorylation of several cellular proteins, including the Src family kinase p53/p56(lyn). In vitro kinase assays showed that Lyn kinase...

  11. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis.

    Science.gov (United States)

    Beauchemin, Nicole; Arabzadeh, Azadeh

    2013-12-01

    The discovery of the carcinoembryonic antigen (CEA) as a tumor marker for colorectal cancer some 50 years ago became the first step in the identification of a much larger family of 12 carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) with surprisingly diverse functions in cell adhesion, in intracellular and intercellular signaling, and during complex biological processes such as cancer progression, inflammation, angiogenesis, and metastasis. The development of proper molecular and biochemical tools and mouse models has enabled bidirectional translation of the CEACAM network biology. Indeed, CEACAM1, CEACAM5, and CEACAM6 are now considered valid clinical biomarkers and promising therapeutic targets in melanoma, lung, colorectal, and pancreatic cancers. These fascinating proteins illustrate how a better understanding of the CEACAM family of cell adhesion molecules reveals their functional link to the underlying disease and lead to new monitoring and targeting opportunities.

  12. 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

  13. Subclinical hypothyroidism: Comparison of adhesion molecule levels before and after levothyroxine therapy.

    Science.gov (United States)

    Bilgir, Ferda; Bilgir, Oktay; Calan, Mehmet; Calan, Ozlem; Isikyakar, Tolgay

    2014-06-01

    Adhesion molecules are involved in inflammation, atherosclerosis and malignancy. This study measured levels of adhesion molecules before and after levothyroxine therapy in patients with subclinical hypothyroidism (SHO). Levels of soluble (s) intracellular adhesion molecule (ICAM)-1, s vascular cell adhesion molecule (sVCAM) VCAM-1 and sE-selectin were analysed in patients diagnosed with SHO, prior to administration of 50 µg/day levothyroxine orally for 3 months. Subsequently, levels of sICAM-1, sVCAM-1 and sE-selectin were reanalysed then compared with the pretreatment levels. In 30 patients with SHO, levels of sICAM-1 were found to be significantly higher than those in healthy controls, (P = 0.001). Post-treatment sICAM-1 levels were significantly lower than pretreatment levels (P = 0.001). No significant differences were found in sVCAM-1 or sE-selectin levels between healthy controls and patients with SHO before treatment, or between patients with SHO pre- and post-treatment. Patients with SHO had significantly higher levels of sICAM-1 compared with controls. Levels became normal after treatment with levothyroxine. These findings emphasize the need for levothyroxine therapy in cases of SHO to normalize sICAM-1 levels. Such treatment helps to prevent the future development of atherosclerosis or cancer. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

    DEFF Research Database (Denmark)

    Damotte, V; Guillot-Noel, L; Patsopoulos, N A

    2014-01-01

    adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes...

  15. Cell Adhesion Molecules of the Immunoglobulin Superfamily in the Nervous System

    DEFF Research Database (Denmark)

    Walmod, Peter Schledermann; Pedersen, Martin Volmer; Berezin, Vladimir

    2007-01-01

    Cell adhesion molecules (CAMs) are proteins mediating cell-cell or cell-extracellular matrix (ECM) interactions. CAMs are traditionally divided into four groups, the cadherins, the selectins, the integrins and CAMs belonging to the immunoglobulin superfamily (IgSF). The present chapter describes...

  16. Cytokines, cytokine antagonists, and soluble adhesion molecules in pediatric OMS and other neuroinflammatory disorders.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A

    2013-03-15

    To test for hypothesized disease- and treatment-induced changes in cytokines and adhesion molecules in children with opsoclonus-myoclonus syndrome (OMS). Multiplex bead assay technology was used for simultaneous measurement of 34 soluble cytokines in cerebrospinal fluid (CSF) and serum. Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA. In total, there were 388 children (239 OMS, 114 controls, and 35 other inflammatory neurological disorders (OIND)). In untreated OMS, mean CSF IL-6 was elevated 2.3-fold, but 67-fold in OIND, without significant differences in other CSF cytokines. Mean serum concentrations of sIL-2Ra (+50%) and CXCL1 (+70%) (pOMS than controls (p=0.005), as was serum CCL11 and IL-13 in treated OMS. Mean CSF CCL4 and IL-1Ra were selectively higher in IVIg-treated OMS (p≤0.0001). CSF sICAM-1 was elevated only in OIND (3.3-fold); serum sICAM-1 was higher in untreated OMS (+21%); and sVCAM-1 was not affected. No correlations with OMS severity or duration were identified. Novel cytokine, cytokine antagonist, and soluble adhesion molecule abnormalities due to OMS or treatment were found. However, the normality of much of the data strengthens previous findings implicating B cell mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule Are Induced by Ionizing Radiation on Lymphatic Endothelium

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Ruiz, María E., E-mail: mrruiz@unav.es [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Garasa, Saray; Rodriguez, Inmaculada [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Solorzano, Jose Luis; Barbes, Benigno [Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Yanguas, Alba [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Department of Biochemistry and Genetics, University of Navarra, Pamplona (Spain); Teijeira, Alvaro; Etxeberria, Iñaki [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Aristu, José Javier [Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Halin, Cornelia [Pharmaceutical Immunology, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich (Switzerland); Melero, Ignacio [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Rouzaut, Ana [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Department of Biochemistry and Genetics, University of Navarra, Pamplona (Spain)

    2017-02-01

    Purpose/Objectives: The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Materials/Methods: Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGFβ in this process anti-TGFβ blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGFβ and /or anti-ICAM1 blocking mAb. Results: We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGFβ. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Conclusion: Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Desmecht D

    2005-08-01

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

  20. ADHESION MOLECULES IN INTESTINAL DESTRUCTIVE-INFLAMMATORY PROCESS IN THE CHILDREN WITH ULCERATIVE COLITIS

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    V. I. Ashkinazi

    2013-01-01

    Full Text Available Aim: to study the content of serum soluble cell adhesion molecules in children with ulcerative colitis that mediate the initial and final stages of the migration of leukocytes to the focus of inflammation: sP-selectin (soluble platelet selectin and Specam-1 (soluble platelet-endothelial cell adhesion molecule 1 as well some earlier unexplored factors associated with their level. Patients and methods: we examined 107 patients with ulcerative colitis aged from 6 up to 17 years. The diagnosis was set on the base of a comprehensive examination. The content of serum soluble adhesion molecules sP-selectin and sPECAM-1 as well cytokine status and neopterin were evaluated by ELISA. Respiratory metabolism was investigated by using chemiluminescent reactions. Results: it was shown that the content of sP-selectin and sPECAM-1 is significantly higher in patients than in the control group, which may influence on the migration of leukocytes into tissues for realization of their effector potential. It is confirmed by morphological analyses of the intestine biopsies, where it was observed the increasing of the number of leukocytes in vascular endothelium and epithelial layer. At the same time strengthening of the oxygen-dependent metabolism of neutrophils, the increase of the concentration of neopterin and tumor necrosis factor α were noted. Conclusions: the correlation of the studied adhesion molecules with a number of inflammatory markers (TNFα (tumor necrosis factor α, free radicals, neopterin was revealed, which indicates the diagnostic value of serum levels of the membrane antigens. The increase of the concentration of adhesion molecules sP-selectin and sPECAM-1 may be one of the links of the pathogenesis of ulcerative colitis. 

  1. Cell-contact-dependent activation of CD4+T cells by adhesion molecules on synovial fibroblasts.

    Science.gov (United States)

    Mori, Masato; Hashimoto, Motomu; Matsuo, Takashi; Fujii, Takao; Furu, Moritoshi; Ito, Hiromu; Yoshitomi, Hiroyuki; Hirose, Jun; Ito, Yoshinaga; Akizuki, Shuji; Nakashima, Ran; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Ohmura, Koichiro; Mimori, Tsuneyo

    2017-05-01

    To determine how cell-cell contact with synovial fibroblasts (SF) influence on the proliferation and cytokine production of CD4 +  T cells. Naïve CD4 +  T cells were cultured with SF from rheumatoid arthritis patients, stimulated by anti-CD3/28 antibody, and CD4 +  T cell proliferation and IFN-γ/IL-17 production were analyzed. To study the role of adhesion molecules, cell contact was blocked by transwell plate or anti-intracellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1(VCAM-1) antibody. To study the direct role of adhesion molecules for CD4 +  T cells, CD161 +  or CD161 - naïve CD4 +  T cells were stimulated on plastic plates coated by recombinant ICAM-1 or VCAM-1, and the source of IFN-γ/IL-17 were analyzed. SF enhanced naïve CD4 +  T cell proliferation and IFN-γ/IL-17 production in cell-contact and in part ICAM-1-/VCAM-1-dependent manner. Plate-coated ICAM-1 and VCAM-1 enhanced naïve CD4 +  T cell proliferation and IFN-γ production, while VCAM-1 efficiently promoting IL-17 production. CD161 +  naïve T cells upregulating LFA-1 and VLA-4 were the major source of IFN-γ/IL-17 upon interaction with ICAM-1/VCAM-1. CD4 +  T cells rapidly expand and secrete IFN-γ/IL-17 upon cell-contact with SF via adhesion molecules. Interfering with ICAM-1-/VCAM-1 may be beneficial for inhibiting RA synovitis.

  2. 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.

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

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    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

  4. Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration and metastasis.

    Science.gov (United States)

    Garrido-Urbani, Sarah; Vonlaufen, Alain; Stalin, Jimmy; De Grandis, Maria; Ropraz, Patricia; Jemelin, Stéphane; Bardin, Florence; Scheib, Holger; Aurrand-Lions, Michel; Imhof, Beat A

    2018-04-01

    Most cancer deaths result from metastasis, which is the dissemination of cells from a primary tumor to distant organs. Metastasis involves changes to molecules that are essential for tumor cell adhesion to the extracellular matrix and to endothelial cells. Junctional Adhesion Molecule C (JAM-C) localizes at intercellular junctions as homodimers or more affine heterodimers with JAM-B. We previously showed that the homodimerization site (E66) in JAM-C is also involved in JAM-B binding. Here we show that neoexpression of JAM-C in a JAM-C-negative carcinoma cell line induced loss of adhesive property and pro-metastatic capacities. We also identify two critical structural sites (E66 and K68) for JAM-C/JAM-B interaction by directed mutagenesis of JAM-C and studied their implication on tumor cell behavior. JAM-C mutants did not bind to JAM-B or localize correctly to junctions. Moreover, mutated JAM-C proteins increased adhesion and reduced proliferation and migration of lung carcinoma cell lines. Carcinoma cells expressing mutant JAM-C grew slower than with JAM-C WT and were not able to establish metastatic lung nodules in mice. Overall these data demonstrate that the dimerization sites E66-K68 of JAM-C affected cell adhesion, polarization and migration and are essential for tumor cell metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Impact of double filtration plasmapheresis on adhesion molecules levels in patients with stable coronary heart disease after coronary stenting.

    Science.gov (United States)

    Tishko, Valerii V; Sokolov, Alexey A; Belskih, Andrei N; Ivanov, Andrei M; Meshkova, Marina E; Skorinova, Tatyana S

    2017-11-01

    Endothelial dysfunction and inflammatory reaction at the site of damage plays a key role in the formation of neointimal hyperplasia, and in the progression of atherosclerosis. The initiating role in these processes is assigned to adhesion molecules. We studied the dynamics of the level of adhesion molecules soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble form of the molecule platelet adhesion and endothelial type-1 (sPECAM-1), sL-, sP-, sE-selectins during double filtration plasmapheresis (DFPP) with use of plasma fractionators (PF) Cascadeflo EC-50W and EC-40W (Asahi Kasei Medical Co., Japan) in patients with stable coronary heart disease and hyperlipidemia-(a) in the early post-implantation period after coronary stenting. DFPP reduces the level of plasma adhesion molecules. When using PF Cascadeflo EC-40W, a more pronounced decrease occurs. The rejection coefficient (RC) of adhesion molecules has been identified for these PF. These RCs reflect the immediate removal efficiency of adhesion molecules in the perfusion of plasma through PF. The removal effectiveness of adhesion molecules when using PF Cascadeflo EC-40W is higher than when using the PF Cascadeflo EC-50W (sICAM-1 - 2.5 times, sVCAM-1 - 2.2 times, sPECAM-1.6 times, sL-selectin - 5 times, sP-selectin - 2.8 times, sE - selectin - 3 times). Reducing adhesion molecule levels when using DFPP may play an important role in correcting of endothelial dysfunction in response to damage to the arterial wall in percutaneous coronary intervention (PCI) during the early post-implantation period after coronary stenting. DFPP is a promising approach to prevent in-stent restenosis (ISR). Copyright © 2017 Elsevier B.V. All rights reserved.

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

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    Nora E.I. El-Bassiouni

    2013-09-01

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

  7. The SALM/Lrfn family of leucine-rich repeat-containing cell adhesion molecules.

    Science.gov (United States)

    Nam, Jungyong; Mah, Won; Kim, Eunjoon

    2011-07-01

    Synaptic adhesion molecules play important roles in various stages of neuronal development, including neurite outgrowth and synapse formation. The SALM (synaptic adhesion-like molecule) family of adhesion molecules, also known as Lrfn, belongs to the superfamily of leucine-rich repeat (LRR)-containing adhesion molecules. Proteins of the SALM family, which includes five known members (SALMs 1-5), have been implicated in the regulation of neurite outgrowth and branching, and synapse formation and maturation. Despite sharing a similar domain structure, individual SALM family proteins appear to have distinct functions. SALMs 1-3 contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. SALM1 directly interacts with NMDA receptors but not with AMPA receptors, whereas SALM2 associates with both NMDA and AMPA receptors. SALMs 1-3 form homo- and heteromeric complexes with each other in a cis manner, whereas SALM4 and SALM5 do not, but instead participate in homophilic, trans-cellular adhesion. SALM3 and SALM5, but not other SALMs, possess synaptogenic activity, inducing presynaptic differentiation in contacting axons. All SALMs promote neurite outgrowth, while SALM4 uniquely increases the number of primary processes extending from the cell body. In addition to these functional diversities, the fifth member of the SALM family, SALM5/Lrfn5, has recently been implicated in severe progressive autism and familial schizophrenia, pointing to the clinical importance of SALMs. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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    David Vansthertem

    2010-01-01

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

  9. The coffee diterpene kahweol inhibits tumor necrosis factor-α-induced expression of cell adhesion molecules in human endothelial cells

    International Nuclear Information System (INIS)

    Kim, Hyung Gyun; Kim, Ji Young; Hwang, Yong Pil; Lee, Kyung Jin; Lee, Kwang Youl; Kim, Dong Hee; Kim, Dong Hyun; Jeong, Hye Gwang

    2006-01-01

    Endothelial cells produce adhesion molecules after being stimulated with various inflammatory cytokines. These adhesion molecules play an important role in the development of atherogenesis. Recent studies have highlighted the chemoprotective and anti-inflammatory effects of kahweol, a coffee-specific diterpene. This study examined the effects of kahweol on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. Kahweol inhibited the adhesion of TNFα-induced monocytes to endothelial cells and suppressed the TNFα-induced protein and mRNA expression of the cell adhesion molecules, VCAM-1 and ICAM-1. Furthermore, kahweol inhibited the TNFα-induced JAK2-PI3K/Akt-NF-κB activation pathway in these cells. Overall, kahweol has anti-inflammatory and anti-atherosclerotic activities, which occurs partly by down-regulating the pathway that affects the expression and interaction of the cell adhesion molecules on endothelial cells

  10. Nitric oxide modulates the expression of endothelial cell adhesion molecules involved in angiogenesis and leukocyte recruitment.

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    Carreau, Aude; Kieda, Claudine; Grillon, Catherine

    2011-01-01

    Tumor angiogenesis and immune response have in common to be cell recognition mechanisms, which are based on specific adhesion molecules and dependent on nitric oxide (NO(•)). The aim of the present study is to deepen the mechanisms of angiogenesis and inflammation regulation by NO(•) to find out the molecular regulation processes that govern endothelial cell permeability and leukocyte transmigration. Effects of NO(•), either exogenous or produced in hypoxic conditions, were studied on microvascular endothelial cells from skin and lymph node because of their strong involvement in melanoma progression. We found that NO(•) down-regulation of pseudo-vessel formation was linked to a decrease in endothelial cell ability to adhere to each other which can be explain, in part, by the inhibition of PECAM-1/CD31 expression. On the other hand, NO(•) was shown to be able to decrease leukocyte adhesion on an endothelial monolayer, performed either in static or in rolling conditions, and to modulate differentially CD34, ICAM-1/CD54, ICAM-2/CD102 and VCAM-1/CD106 expression. In conclusion, during angiogenesis and leukocyte recruitment, NO(•) regulates cell interactions by controlling adhesion molecule expression and subsequently cell adhesion. Moreover, each endothelial cell type presents its own organospecific response to NO(•), reflecting the functions of the tissue they originate from. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. [Effect of female steroid hormones on expression of adhesion molecules by peripheral blood leukocytes].

    Science.gov (United States)

    Chernyshov, V P; Vodianyk, M O; Hrekova, S P

    2002-01-01

    The specific adhesion of cells to other cells or to extracellular matrices is a basic component of cell migration and recognition, and it underlies a lot of biologic processes including embryogenesis, tissue repair, and both immune and inflammatory responses. The aim of this study was to investigate the influence of female steroid hormones on expression of the adhesion molecules on the leukocytes. The whole blood from healthy people was incubated in a presence or an absence of progesterone (2 micrograms/ml) or 17 beta-estradiol (0.2 microgram/ml) for 4 h., and then with TNF for 18 h. The phenotype of the leukocytes was investigated by flow cytometry. Progesterone inhibited an expression of CD54 on monocytes and lymphocytes due to reducing density of these molecules on the cellular surface; 17 beta-estradiol inhibited an expression of CD54 on monocytes and CD69 molecules on monocytes and lymphocytes due to reducing density of these molecules on the cellular surface. Progesterone inhibited TNF-stimulated CD54 and CD11b expression on the granulocytes and CD69 expression on lymphocytes by reducing partly the density of these molecules on the surface of cells, and in such way it partly blocked the proinflammatory activity of this cytokine. Progesterone also reduced CD62L expression on the granulocytes by reducing an amount of a marker, positive to those cells but enhanced the effect of TNF. The data obtained evidence that female steroid hormones take part in the regulation of an expression of adhesion molecules by the leukocytes and are likely to be important in the circulation and activation of the leucocytes.

  12. Soluble endothelial cell-selective adhesion molecule and incident cardiovascular events in a multiethnic population.

    Science.gov (United States)

    Ren, Hao-Yu; Khera, Amit; de Lemos, James A; Ayers, Colby R; Rohatgi, Anand

    2017-09-01

    Cell adhesion molecules are key regulators of atherosclerotic plaque development, but circulating levels of soluble fragments, such as intercellular adhesion molecule (sICAM-1) and vascular cell adhesion molecule (sVCAM-1), have yielded conflicting associations with atherosclerotic cardiovascular disease (ASCVD). Endothelial cell-selective adhesion molecule (ESAM) is expressed exclusively in platelets and endothelial cells, and soluble ESAM (sESAM) levels have been associated with prevalent subclinical atherosclerosis. We therefore hypothesized that sESAM would be associated with incident ASCVD. sESAM, sICAM-1, and sVCAM-1 were measured in 2,442 participants without CVD in the Dallas Heart Study, a probability-based population sample aged 30-65 years enrolled between 2000 and 2002. ASCVD was defined as first myocardial infarction, stroke, coronary revascularization, or CV death. A total of 162 ASCVD events were analyzed over 10.4 years. Increasing sESAM was associated with ASCVD, independent of risk factors (HR Q4 vs Q1: 2.7, 95% CI 1.6-4.6). Serial adjustment for renal function, sICAM-1, VCAM-1, and prevalent coronary calcium did not attenuate these associations. Continuous ESAM demonstrated similar findings (HR 1.31, 95% CI 1.2-1.4). Addition of sESAM to traditional risk factors improved discrimination and reclassification (delta c-index: P = .009; integrated-discrimination-improvement index P = .001; net reclassification index = 0.42, 95% CI 0.15-0.68). Neither sICAM-1 nor sVCAM-1 was independently associated with ASCVD. sESAM but not sICAM-1 or sVCAM-1 levels are associated with incident ASCVD. Further studies are warranted to investigate the role of sESAM in ASCVD. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Endothelial vascular cell adhesion molecule 1 expression is suppressed by melanoma and carcinoma

    OpenAIRE

    1995-01-01

    Vascular cell adhesion molecule 1 (VCAM-1) mediates extravasation of circulating leukocytes into inflamed tissues, and presumably, plays a role in the immigration of cytotoxic effector lymphocytes into tumor metastases. Since metastases are rarely cleared by blood-borne cells from the immune system, we asked whether the tumor may escape host defense by interfering with the mechanism of effector cell extravasation. Here we show that in mice and humans, VCAM-1 expression is repressed on tumor-i...

  14. Endothelial Adhesion Molecules and Multiple Organ Failure in Patients With Severe Sepsis

    Science.gov (United States)

    Amalakuhan, Bravein; Habib, Sheila A.; Mangat, Mandeep; Reyes, Luis F.; Rodriguez, Alejandro H.; Hinojosa, Cecilia A.; Soni, Nilam J.; Gilley, Ryan P.; Bustamante, Carlos A.; Anzueto, Antonio; Levine, Stephanie M.; Peters, Jay I.; Aliberti, Stefano; Sibila, Oriol; Chalmers, James D.; Torres, Antoni; Waterer, Grant W.; Martin-Loeches, Ignacio; Bordon, Jose; Blanquer, Jose; Sanz, Francisco; Marcos, Pedro J.; Rello, Jordi; Ramirez, Julio; Solé-Violán, Jordi; Luna, Carlos M.; Feldman, Charles; Witzenrath, Martin; Wunderink, Richard G.; Stolz, Daiana; Wiemken, Tim L.; Shindo, Yuichiro; Dela Cruz, Charles S.; Orihuela, Carlos J.; Restrepo, Marcos I.

    2016-01-01

    Objective To determine if serum levels of endothelial adhesion molecules were associated with the development of multiple organ failure (MOF) and in-hospital mortality in adult patients with severe sepsis. Design This study was a secondary data analysis of a prospective cohort study. Setting Patients were admitted to two tertiary intensive care units in San Antonio, TX, between 2007 and 2012. Patients Patients with severe sepsis at the time of intensive care unit (ICU) admission were enrolled. Inclusion criteria were consistent with previously published criteria for severe sepsis or septic shock in adults. Exclusion criteria included immunosuppressive medications or conditions. Interventions None. Measurements Baseline serum levels of the following endothelial cell adhesion molecules were measured within the first 72 hours of ICU admission: Intracellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Vascular Endothelial Growth Factor (VEGF). The primary and secondary outcomes were development of MOF (≥2 organ dysfunction) and in-hospital mortality, respectively. Main results Forty-eight patients were enrolled in this study, of which 29 (60%) developed MOF. Patients that developed MOF had higher levels of VCAM-1 (p=0.01) and ICAM-1 (p=0.01), but not VEGF (p=0.70) compared with patients without MOF (single organ failure only). The area under the curve (AUC) to predict MOF according to VCAM-1, ICAM-1 and VEGF was 0.71, 0.73, and 0.54, respectively. Only increased VCAM-1 levels were associated with in-hospital mortality (p=0.03). These associations were maintained even after adjusting for APACHE and SOFA scores using logistic regression. Conclusions High levels of serum ICAM-1 was associated with the development of MOF. High levels of VCAM-1 was associated with both MOF and in-hospital mortality. PMID:27701021

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

    Bos-Veneman, Netty G P; Bijzet, Johan; Limburg, Pieter C; Minderaa, Ruud B; Kallenberg, Cees G; Hoekstra, Pieter J

    2010-12-01

    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. Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, soluble IL-2 receptor (sIL2R), tumor necrosis factor (TNF)-α, interferon (IFN)-γ, soluble vascular cell adhesion molecule-1 (sVCAM-1), and intercellular adhesion molecule-1 (sICAM-1) of 66 children and adolescents with a tic disorder and 71 healthy volunteers were compared. We also addressed possible relations between concentrations of the immune markers and severity of tics and comorbid obsessive-compulsive symptoms. Median serum concentrations did not differ significantly between patients and healthy subjects. Serum IL-2 concentrations were positively associated with tic severity ratings; serum IL-12 concentrations negatively with severity ratings of obsessive-compulsive symptoms. These preliminary findings do not reveal major immune activation in children with a tic disorder but may suggest more subtle disturbances related to disease expression. Copyright © 2010 Elsevier Inc. All rights reserved.

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

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    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.

  18. Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity

    Science.gov (United States)

    Shin, Hyewon; van Riesen, Christoph; Whitcomb, Daniel; Warburton, Julia M.; Jo, Jihoon; Kim, Doyoun; Kim, Sun Gyun; Um, Seung Min; Kwon, Seok-kyu; Kim, Myoung-Hwan; Roh, Junyeop Daniel; Woo, Jooyeon; Jun, Heejung; Lee, Dongmin; Mah, Won; Kim, Hyun; Kaang, Bong-Kiun; Cho, Kwangwook; Rhee, Jeong-Seop; Choquet, Daniel; Kim, Eunjoon

    2016-01-01

    Summary Synaptic adhesion molecules regulate synapse development and plasticity through mechanisms including trans-synaptic adhesion and recruitment of diverse synaptic proteins. We report here that the immunoglobulin superfamily member 11 (IgSF11), a homophilic adhesion molecule preferentially expressed in the brain, is a novel and dual-binding partner of the postsynaptic scaffolding protein PSD-95 and AMPAR glutamate receptors (AMPARs). IgSF11 requires PSD-95 binding for its excitatory synaptic localization. In addition, IgSF11 stabilizes synaptic AMPARs, as shown by IgSF11 knockdown-induced suppression of AMPAR-mediated synaptic transmission and increased surface mobility of AMPARs, measured by high-throughput, single-molecule tracking. IgSF11 deletion in mice leads to suppression of AMPAR-mediated synaptic transmission in the dentate gyrus and long-term potentiation in the CA1 region of the hippocampus. IgSF11 does not regulate the functional characteristics of AMPARs, including desensitization, deactivation, or recovery. These results suggest that IgSF11 regulates excitatory synaptic transmission and plasticity through its tripartite interactions with PSD-95 and AMPARs. PMID:26595655

  19. 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.

  20. Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers?

    Science.gov (United States)

    Erturk, Kayhan; Tastekin, Didem; Bilgin, Elif; Serilmez, Murat; Bozbey, Hamza Ugur; Sakar, Burak

    2016-02-01

    Cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors. The purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule-1 (ALCAM) and intercellular adhesion molecule-1 (ICAM-1) in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). The median age at diagnosis was 59.5 years (range 32-82 years). Tumor localizations of the majority of the patients were antrum (n=42, 72.4%) and tumor histopathologies of the majority of the patients were diffuse (n=43, 74.1%). The majority of the patients had stage IV disease (n=41, 70.7%). Thirty six (62.1%) patients had lymph node involvement. The median follow-up time was 66 months (range 1-97.2 months). At the end of the observation period, 26 patients (44.8%) were dead. The median survival for all patients was 21.4±5 months (%95 CI, 11.5-31.3). The 1-year survival rates were 66.2%. The baseline serum ALCAM levels of the patients were significantly higher than those of the controls (p=0.001). There was no significant difference in the serum levels of ICAM-1 between the patients and controls (p=0.232). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p>0.05). Tumor localization (p=0.03), histopathology (p=0.05), and response to chemotherapy (p=0.003) had prognostic factors on survival. Neither serum ALCAM levels nor serum ICAM-1 levels were identified to have a prognostic role on overall survival (ICAM-1 p=0.6, ALCAM p=0.25). In conclusion, serum levels of ALCAM were found to have diagnostic value in GC patients. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2009-06-22

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

  2. 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

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

    DEFF Research Database (Denmark)

    Riley, Caroline Hasselbalch; 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...

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

    International Nuclear Information System (INIS)

    Grégoire, Geneviève; Sharrock, Patrick; Delannée, Mathieu; Delisle, Marie-Bernadette

    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: ► Non-freezable water exists in demineralized dentine. ► Free water can be removed by ethanol rinse of the demineralized collagen. ► Ethanol wet bonding leads to a homogeneous hybrid layer free of defects.

  5. 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.

  6. 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.

  7. The role of cell adhesion molecules in brain wiring and neuropsychiatric disorders.

    Science.gov (United States)

    Sakurai, Takeshi

    2017-06-01

    Cell adhesion molecules (CAMs) in the nervous system have long been a research focus, but many mice lacking CAMs show very subtle phenotypes, giving an impression that CAMs may not be major players in constructing the nervous system. However, recent human genetic studies suggest CAM involvement in many neuropsychiatric disorders, implicating that they must have significant functions in nervous system development, namely in circuitry formation. As CAMs can provide specificity through their molecular interactions, this review summarizes possible mechanisms on how alterations of CAMs can result in neuropsychiatric disorders through circuitry modification. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Ukkonen, Maritta; Wu, Xingchen; Reipert, Birgit

    2007-01-01

    OBJECTIVE: We evaluated the utility of adhesion molecule (AM) and cytokine/chemokine expressions in blood and cerebrospinal fluid (CSF) as markers of disease activity in primary progressive multiple sclerosis (PPMS). METHODS: The expressions of AMs and the levels of 17 cytokines in patients...... with PPMS (n = 25) were compared with those in secondary progressive MS (SPMS) (n = 18) and controls (n =11) and correlated with the volumes of focal and atrophic changes on MRI. RESULTS: The expressions of very late activation antigen 4 (VLA-4), lymphocyte function-associated antigen 1 (LFA-1...

  9. Leucine-rich repeat-containing synaptic adhesion molecules as organizers of synaptic specificity and diversity.

    Science.gov (United States)

    Schroeder, Anna; de Wit, Joris

    2018-04-09

    The brain harbors billions of neurons that form distinct neural circuits with exquisite specificity. Specific patterns of connectivity between distinct neuronal cell types permit the transfer and computation of information. The molecular correlates that give rise to synaptic specificity are incompletely understood. Recent studies indicate that cell-surface molecules are important determinants of cell type identity and suggest that these are essential players in the specification of synaptic connectivity. Leucine-rich repeat (LRR)-containing adhesion molecules in particular have emerged as key organizers of excitatory and inhibitory synapses. Here, we discuss emerging evidence that LRR proteins regulate the assembly of specific connectivity patterns across neural circuits, and contribute to the diverse structural and functional properties of synapses, two key features that are critical for the proper formation and function of neural circuits.

  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. Expression of adhesion molecules and the proliferative activity of carcinosarcoma of the ovary.

    Science.gov (United States)

    Hirano, Hiroshi; Kizaki, Tomohiko; Ito, Takashi; Okimura, Akira; Yamanegi, Koji; Nakasho, Keiji

    2014-12-01

    To clarify the mechanism underlying the formation of a sarcomatous component of ovarian carcinosarcoma, we investigated the expression of adhesion molecules and the proliferative activity of carcinosarcomas. We immunohistochemically examined the expression of E-cadherin and β-catenin, and the Ki-67 labeling index (Ki-67 LI) in six carcinosarcomas containing endometrioid carcinoma as a carcinomatous component. The sarcomatous components of the carcinosarcomas did not express E-cadherin or β-catenin. All carcinomatous components expressed these molecules but the expression was reduced compared to that in endometrioid ovarian carcinomas. In five of the six carcinosarcomas, the Ki-67 LI of the sarcomatous component was less than that of the carcinomatous component. The present results suggest that a carcinomatous component transforms more easily than an ordinary endometrioid carcinoma from the viewpoint of the cell adhesion, and cells in a carcinomatous component continuously transform into sarcomatous cells during the growth of carcinosarcoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. The Role of Cell Adhesion Molecule Genes Regulating Neuroplasticity in Addiction

    Directory of Open Access Journals (Sweden)

    Dawn E. Muskiewicz

    2018-01-01

    Full Text Available A variety of genetic approaches, including twin studies, linkage studies, and candidate gene studies, has established a firm genetic basis for addiction. However, there has been difficulty identifying the precise genes that underlie addiction liability using these approaches. This situation became especially clear in genome-wide association studies (GWAS of addiction. Moreover, the results of GWAS brought into clarity many of the shortcomings of those early genetic approaches. GWAS studies stripped away those preconceived notions, examining genes that would not previously have been considered in the study of addiction, consequently creating a shift in our understanding. Most importantly, those studies implicated a class of genes that had not previously been considered in the study of addiction genetics: cell adhesion molecules (CAMs. Considering the well-documented evidence supporting a role for various CAMs in synaptic plasticity, axonal growth, and regeneration, it is not surprising that allelic variation in CAM genes might also play a role in addiction liability. This review focuses on the role of various cell adhesion molecules in neuroplasticity that might contribute to addictive processes and emphasizes the importance of ongoing research on CAM genes that have been implicated in addiction by GWAS.

  13. 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.

  14. Junctional Adhesion Molecule (JAM)-C Deficient C57BL/6 Mice Develop a Severe Hydrocephalus

    Science.gov (United States)

    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 3rd 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. PMID:23029139

  15. The Cytolytically Inactive Terminal Complement Complex Activates Endothelial Cells to Express Adhesion Molecules and Tissue Factor Procoagulant Activity

    Science.gov (United States)

    Tedesco, Francesco; Pausa, Mario; Nardon, Ermanno; Introna, Martino; Mantovani, Alberto; Dobrina, Aldo

    1997-01-01

    The membrane attack complex of complement (C) in sublytic concentrations stimulates endothelial cells (EC) to express adhesion molecules and to release biologically active products. We have examined the ability of a cytolytically inactive form of this complex, which is incapable of inserting into the cell membrane, to upregulate the expression of adhesion molecules and of tissue factor (TF) procoagulant activity. The inactive terminal C complex (iTCC) was prepared by mixing C5b6, C7, C8, and C9 and was purified by fast protein liquid chromatography on a Superose 12 column. Binding of this complex to EC was found to be dose dependent and was inhibited by anti-C9 antibodies, as assessed both by ELISA using an mAb anti-C9 neoantigen and by measuring cell-bound 125I-labeled iTCC. Exposure of EC to iTCC resulted in a dose- and time-dependent expression of endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 accompanied by increased levels of the corresponding mRNA, but not in the rapid expression of P-selectin. Inactive TCC also induced increased TF activity evaluated by a chromogenic assay that measures the formation of factor Xa. These effects were inhibited by anti-C9 antibodies. The data support the conclusion that iTCC may induce proinflammatory and procoagulant activities on EC. PMID:9151899

  16. Serum of patients with antiphospholipid syndrome induces adhesion molecules in endothelial cells.

    Science.gov (United States)

    Engel, Bettina; Müller, Gregor; Roch, Beate; Schröder, Hans-Egbert; Aringer, Martin; Bornstein, Stefan R; Morawietz, Henning

    2017-11-01

    The antiphospholipid syndrome (APS) is a systemic auto-immune disease with an unclear pathophysiology. The aim of our study was to understand the development of APS on a cellular level. Therefore, we analyzed the influence of human serum of APS patients on endothelial expression of specific genes and proteins in comparison to a control group. In this study, we analyzed the expression of ICAM-1, VCAM-1, E-selectin and annexin V in primary cultures of human umbilical vein endothelial cells (HUVEC) in response to 10% (v/v) serum of control patients (n = 6), patients with systemic lupus erythematosus (SLE) and no APS (n = 4) or APS patients (n = 9) for 24 h. Total RNA was prepared from confluent endothelial cell layers and mRNA expression of ICAM-1, VCAM-1 and E-selectin was analyzed by reverse transcription polymerase-chain reaction (RT-PCR). The protein expression was determined by Western blot. Serum protein concentrations of soluble forms of adhesion molecules sICAM-1 and sVCAM-1 were quantified by ELISA. Gene expression data were correlated with clinical parameters. The mRNA expression of ICAM-1 was increased in cells incubated with serum from APS patients (166 ± 22% of control; P = 0.023). Serum of patients with (SLE)/no APS caused a 1.4-fold higher ICAM-1 mRNA level. Western blot analysis showed an increase in protein expression of adhesion molecules ICAM-1 (260 ± 49%; P = 0.011) and VCAM-1 (357 ± 97%; P = 0.023) in cells that were incubated with serum from APS patients. Plasma analysis showed elevated levels of sVCAM-1 in APS patients (189 ± 34%; P = 0.045) compared to the levels measured in the control group. The sVCAM-1 plasma level was correlating with the frequency of abortions. An augmented expression of endothelial adhesion molecules is involved in the pathophysiology of patients with antiphospholipid syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The neural plasticity theory of depression: assessing the roles of adult neurogenesis and PSA-NCAM within the hippocampus.

    Science.gov (United States)

    Wainwright, Steven R; Galea, Liisa A M

    2013-01-01

    Depression is a devastating and prevalent disease, with profound effects on neural structure and function; however the etiology and neuropathology of depression remain poorly understood. Though antidepressant drugs exist, they are not ideal, as only a segment of patients are effectively treated, therapeutic onset is delayed, and the exact mechanism of these drugs remains to be elucidated. Several theories of depression do exist, including modulation of monoaminergic neurotransmission, alterations in neurotrophic factors, and the upregulation of adult hippocampal neurogenesis, and are briefly mentioned in the review. However none of these theories sufficiently explains the pathology and treatment of depression unto itself. Recently, neural plasticity theories of depression have postulated that multiple aspects of brain plasticity, beyond neurogenesis, may bridge the prevailing theories. The term "neural plasticity" encompasses an array of mechanisms, from the birth, survival, migration, and integration of new neurons to neurite outgrowth, synaptogenesis, and the modulation of mature synapses. This review critically assesses the role of adult hippocampal neurogenesis and the cell adhesion molecule, PSA-NCAM (which is known to be involved in many facets of neural plasticity), in depression and antidepressant treatment.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    concentration in aged muscle was sixfold higher than in young adult muscle. In contrast with previous reports, NCAM polypeptides of 200, 145, 125 and 120 kDa were observed by immunoblotting throughout postnatal development and aging, the relative proportions of the individual NCAM polypeptides remaining...... 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.......9 kb were present in perinatal and young adult skeletal muscle, whereas only the 5.2 and 2.9 kb mRNA classes could be demonstrated in aged muscle. This indicates that metabolism of the various NCAM polypeptides is individually regulated during aging. Alternative splicing of NCAM mRNA in skeletal muscle...

  19. 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.

  20. 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.

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

    DEFF Research Database (Denmark)

    Andersson, A M; Moran, N; Gaardsvoll, H

    1991-01-01

    . Conversely, no NCAM protein synthesis is observed in BT4Cn cells, even though NCAM mRNA is expressed. Thus, development of an increased metastatic capacity is accompanied by the disappearance of NCAM protein expression in this model system. The functional importance of NCAM expression was studied by a cell...

  2. 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...

  3. Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.

    Science.gov (United States)

    Huang, Chi-Wei; Tsai, Meng-Han; Chen, Nai-Ching; Chen, Wei-Hsi; Lu, Yan-Ting; Lui, Chun-Chung; Chang, Ya-Ting; Chang, Wen-Neng; Chang, Alice Y W; Chang, Chiung-Chih

    2015-11-25

    Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.

  4. Circulating Cellular Adhesion Molecules and Cognitive Function: The Coronary Artery Risk Development in Young Adults Study.

    Science.gov (United States)

    Yoon, Cynthia Yursun; Steffen, Lyn M; Gross, Myron D; Launer, Lenore J; Odegaard, Andrew; Reiner, Alexander; Sanchez, Otto; Yaffe, Kristine; Sidney, Stephen; Jacobs, David R

    2017-01-01

    Higher circulating concentrations of cellular adhesion molecules (CAMs) can be used as markers of endothelial dysfunction. Given that the brain is highly vascularized, we assessed whether endothelial function is associated with cognitive performance. Within the Coronary Artery Risk Development in Young Adults (CARDIA) Study, excluding N  = 54 with stroke before year 25, we studied CAMs among N  = 2,690 black and white men and women in CARDIA year 7 (1992-1993, ages 25-37) and N  = 2,848 in CARDIA year 15 (2000-2001, ages 33-45). We included subjects with levels of circulating soluble CAMs measured in year 7 or 15 and cognitive function testing in year 25 (2010-2011, ages 43-55). Using multiple regression analysis, we evaluated the association between CAMs and year 25 cognitive test scores: Rey Auditory Verbal Learning Test (RAVLT, memory), Digit Symbol Substitution Test (DSST, speed of processing), and the Stroop Test (executive function). All CAM concentrations were greater in year 15 vs. year 7. Adjusting for age, race, sex, education, smoking, alcohol, diet, physical activity, participants in the fourth vs. the first quartile of CARDIA year 7 of circulating intercellular adhesion molecule-1 (ICAM-1) scored worse on RAVLT, DSST, and Stroop Test ( p  ≤ 0.05) in CARDIA year 25. Other CAMs showed little association with cognitive test scores. Findings were similar for ICAM-1 assessed at year 15. Adjustment for possibly mediating physical factors attenuated the findings. Higher circulating ICAM-1 at average ages 32 and 40 was associated with lower cognitive skills at average age 50. The study is consistent with the hypothesis that endothelial dysfunction is associated with worse short-term memory, speed of processing, and executive function.

  5. Circulating Cellular Adhesion Molecules and Cognitive Function: The Coronary Artery Risk Development in Young Adults Study

    Directory of Open Access Journals (Sweden)

    Cynthia Yursun Yoon

    2017-05-01

    Full Text Available ObjectiveHigher circulating concentrations of cellular adhesion molecules (CAMs can be used as markers of endothelial dysfunction. Given that the brain is highly vascularized, we assessed whether endothelial function is associated with cognitive performance.MethodWithin the Coronary Artery Risk Development in Young Adults (CARDIA Study, excluding N = 54 with stroke before year 25, we studied CAMs among N = 2,690 black and white men and women in CARDIA year 7 (1992–1993, ages 25–37 and N = 2,848 in CARDIA year 15 (2000–2001, ages 33–45. We included subjects with levels of circulating soluble CAMs measured in year 7 or 15 and cognitive function testing in year 25 (2010–2011, ages 43–55. Using multiple regression analysis, we evaluated the association between CAMs and year 25 cognitive test scores: Rey Auditory Verbal Learning Test (RAVLT, memory, Digit Symbol Substitution Test (DSST, speed of processing, and the Stroop Test (executive function.ResultAll CAM concentrations were greater in year 15 vs. year 7. Adjusting for age, race, sex, education, smoking, alcohol, diet, physical activity, participants in the fourth vs. the first quartile of CARDIA year 7 of circulating intercellular adhesion molecule-1 (ICAM-1 scored worse on RAVLT, DSST, and Stroop Test (p ≤ 0.05 in CARDIA year 25. Other CAMs showed little association with cognitive test scores. Findings were similar for ICAM-1 assessed at year 15. Adjustment for possibly mediating physical factors attenuated the findings.ConclusionHigher circulating ICAM-1 at average ages 32 and 40 was associated with lower cognitive skills at average age 50. The study is consistent with the hypothesis that endothelial dysfunction is associated with worse short-term memory, speed of processing, and executive function.

  6. Histamine inhibits high mobility group box 1-induced adhesion molecule expression on human monocytes.

    Science.gov (United States)

    Takahashi, Hideo; Sadamori, Hiroshi; Teshigawara, Kiyoshi; Niwa, Atsuko; Liu, Keyue; Wake, Hidenori; Mori, Shuji; Yoshino, Tadashi; Nishibori, Masahiro

    2013-10-15

    Cell-cell interaction through binding of adhesion molecules on monocytes to their ligands on T-cells plays roles in cytokine production and lymphocyte proliferation. High mobility group box 1 (HMGB1), an abundant and conserved nuclear protein, acts in the extracellular environment as a primary pro-inflammatory signal. HMGB1 induces expression of intercellular adhesion molecule (ICAM), B7.1, B7.2 and CD40 on monocytes, resulting in production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α production and lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs). Histamine inhibits pro-inflammatory cytokine production via histamine H2-receptors; however, it is not known whether histamine inhibits HMGB1 activity. This study was designed to study the inhibitory effect of histamine on HMGB1 activity. We examined the effect of histamine on HMGB1-induced expression of ICAM-1, B7.1, B7.2 and CD40 on monocytes, production of IFN-γ and TNF-α and lymphocyte proliferation in PBMCs. Histamine inhibited HMGB1 activity in a concentration-dependent manner. The effects of histamine were partially ablated by the H2-receptor antagonist, famotidine, and mimicked by the H2/H4-receptor agonists, dimaprit and 4-methylhistamine. Histamine induced cyclic adenosine monophosphate (cAMP) production in the presence and absence of HMGB1. The effects of histamine were reversed by the protein kinase A (PKA) inhibitor, H89, and mimicked by the membrane-permeable cAMP analog, dibutyryl cAMP (dbcAMP), and the adenylate cyclase activator, forskolin. These results together indicated that histamine inhibited HMGB1 activity. © 2013 Elsevier B.V. All rights reserved.

  7. A positive correlation between expression of beta 1-integrin cell adhesion molecules and fertilizing ability of human spermatozoa in vitro.

    Science.gov (United States)

    Klentzeris, L D; Fishel, S; McDermott, H; Dowell, K; Hall, J; Green, S

    1995-03-01

    The purpose of this study was to investigate firstly whether beta 1-integrin cell adhesion molecules are expressed by human spermatozoa, and secondly whether there is any relationship between the expression of beta 1-integrin cell adhesion molecules and the fertilizing ability of human spermatozoa in vitro. A total of 50 semen samples were examined. The samples were obtained from the male partners of couples undergoing in-vitro fertilization (IVF) for either unexplained, tubal or male factor infertility. A panel of six monoclonal antibodies against beta 1-integrin cell adhesion molecules and immunohistochemical techniques were used to identify the presence of these molecules on the spermatozoa. The percentage of spermatozoa showing strong immunolabelling with each monoclonal antibody was assessed in each sample. The relationship between these results and the aetiology of infertility and incidence of fertilization was examined. beta 1-Integrins, and primarily the ones with alpha 4-, alpha 5- and alpha 6-chains, were expressed by human spermatozoa. Compared with semen samples from unexplained or male factor infertility patients, samples from tubal infertility patients had a significantly higher (P fertilizing ability of spermatozoa. The positive correlation between the presence of certain beta 1-integrin cell adhesion molecules and the fertilizing ability of human spermatozoa suggests that integrins may be putative determinants in egg-sperm recognition and interaction.

  8. The synaptic cell adhesion molecule, SynCAM1, mediates astrocyte-to-astrocyte and astrocyte-to-GnRH neuron adhesiveness in the mouse hypothalamus.

    Science.gov (United States)

    Sandau, Ursula S; Mungenast, Alison E; McCarthy, Jack; Biederer, Thomas; Corfas, Gabriel; Ojeda, Sergio R

    2011-06-01

    We previously identified synaptic cell adhesion molecule 1 (SynCAM1) as a component of a genetic network involved in the hypothalamic control of female puberty. Although it is well established that SynCAM1 is a synaptic adhesion molecule, its contribution to hypothalamic function is unknown. Here we show that, in addition to the expected neuronal localization illustrated by its presence in GnRH neurons, SynCAM1 is expressed in hypothalamic astrocytes. Cell adhesion assays indicated that SynCAM is recognized by both GnRH neurons and astrocytes as an adhesive partner and promotes cell-cell adhesiveness via homophilic, extracellular domain-mediated interactions. Alternative splicing of the SynCAM1 primary mRNA transcript yields four mRNAs encoding membrane-spanning SynCAM1 isoforms. Variants 1 and 4 are predicted to be both N and O glycosylated. Hypothalamic astrocytes and GnRH-producing GT1-7 cells express mainly isoform 4 mRNA, and sequential N- and O-deglycosylation of proteins extracted from these cells yields progressively smaller SynCAM1 species, indicating that isoform 4 is the predominant SynCAM1 variant expressed in astrocytes and GT1-7 cells. Neither cell type expresses the products of two other SynCAM genes (SynCAM2 and SynCAM3), suggesting that SynCAM-mediated astrocyte-astrocyte and astrocyte-GnRH neuron adhesiveness is mostly mediated by SynCAM1 homophilic interactions. When erbB4 receptor function is disrupted in astrocytes, via transgenic expression of a dominant-negative erbB4 receptor form, SynCAM1-mediated adhesiveness is severely compromised. Conversely, SynCAM1 adhesive behavior is rapidly, but transiently, enhanced in astrocytes by ligand-dependent activation of erbB4 receptors, suggesting that erbB4-mediated events affecting SynCAM1 function contribute to regulate astrocyte adhesive communication.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  10. 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...

  11. Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion

    DEFF Research Database (Denmark)

    Odum, Niels; Yoshizumi, H; Okamoto, Y

    1992-01-01

    was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation...

  12. Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells.

    Science.gov (United States)

    Asci, Gulay; Basci, Ali; Shah, Sudhir V; Basnakian, Alexei; Toz, Huseyin; Ozkahya, Mehmet; Duman, Soner; Ok, Ercan

    2008-12-01

    Presence of accelerated atherosclerosis in dialysis patients cannot be entirely explained by conventional risk factors. Exposure to urea, which is elevated in patients with kidney disease, leads to the carbamylation of proteins. We investigated the effects of carbamylated low-density lipoprotein (cLDL) on human coronary artery vascular smooth muscle cells (VSMC). Native LDL (nLDL) was carbamylated with potassium cyanate. Cells were incubated with different concentrations of cLDL carbamylated at different time points. Cytotoxicity, apoptosis, proliferation (bromodeoxyuridine incorporation), expression of adhesion molecules and extracellular matrix protein synthesis were studied. Carbamylated low-density lipoprotein exposure leads to morphological alterations and presence of cellular debris. Neither nLDL nor cLDL caused apoptosis. Lactate dehydrogenase (LDH) release was not different between groups. Carbamylated low-density lipoprotein led to a striking proliferation in VSMC compared to nLDL. Carbamylated low-density lipoprotein significantly increased intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression compared to the control. The effects of cLDL on proliferation and adhesion molecule expression were dose-dependent and correlated with the degree of low-density lipoprotein carbamylation. cLDL had no effect on extracellular matrix protein synthesis. The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.

  13. [Adhesion molecules and mononuclear cell subpopulations in the coronary and pulmonary arteries of patients with coronary heart disease].

    Science.gov (United States)

    Chumachenko, P V; Ivanova, A G; Belokon, E V; Akchurin, R S

    2015-01-01

    Atherosclerosis is a multifactor disease, in which dysfunction of the endothelium leads to the emergence of its adhesion molecules. to investigate the expression of the endothelial adhesion molecules PECAM (CD31), ICAM, and VCAM, as well as adherent endothelial T cells and monocytes. The material examined was en face pulmonary and coronary artery samples taken during autopsies (10 men), and en face specimens obtained from the coronary artery fragments taken from coronary heart disease patients during endarterectomy (37 men). This investigation used antibodies to the adhesion molecules ICAM-1, VCAM-1, and PECAM and those to CD3, CD4, CD8 T-cells and CD68 monocytes. The endothelial cells in the atherosclerotically intact coronary arteries had an elongated shape and were aligned along the blood flow. Those located above atheromas and fibroatheromas changed their shape from elongated to polygonal. Above the fatty streaks and atheromas, the reaction with antibodies to CD31 antigens became weaker at the edge of endothelial cells and disappeared in places. While the atherosclerotic process progressed, the reaction with the CD31 antigen at the edge of endothelial cells was similar in intensity to that on the surface of the endothelium. Adhesion of T cells and monocytes to the endothelium of coronary arteries increased as the atherosclerotic vascular process progressed. T cells and monocytes more often adhered to the endothelium at the sites where the endothelial cells contacted each other. Heterogeneity was found in the endothelial cells: their shape, the expression of adhesion molecules, and the adhesion of lymphocytes and monocytes to them changed during the progression of the atherosclerotic process.

  14. [Estimation of relation between homocysteine concentration and selected lipid parameters and adhesion molecules concentration in children with atherosclerosis risk factors].

    Science.gov (United States)

    Sierakowska-Fijałek, Anna; Baj, Zbigniew; Kaczmarek, Piotr; Stepień, Mariusz; Rysz, Jacek

    2008-10-01

    Atherosclerosis begins in childhood. At present among numerous risk factors of atherosclerosis the role of hiperhomocysteinemia in development of cardiovascular heart disease is taken under consideration. Atherogenic effect of homocystein is related to its cytotoxin action, conducting to endothelial dysfunction and damage. It is correlated with increase of the lipid levels in the blood serum and change of expression of the soluble forms of adhesion molecules. The aim of this study was to estimate relations between the homocystein serum concentration, expression of the selected adhesion molecules and the lipid levels in the blood serum in children with atherosclerosis risk factors. The group consisted of 670 children, 76 of them had atherosclerosis risk factors. In further examination 48 children have taken a part, whose parents were agreed for theirs participation in the program. The comparative group composed of 25 children without the risk factors. We determined total cholesterol (TC), triglycerides (TG), LDL cholesterol fraction (LDL-C), HDL cholesterol fraction (HDL-C), serum homocysteine concentration (Hcy), the expression of the soluble forms of adhesion molecules (sCAM): sP-selectin and sVCAM-1 (vascular cell adhesion molecule-1). Obesity, hypertension and lipid disorders in the shape of higher concentration of TC, LDL-C, TG and lower HDL-C were the most frequent risk factors in the investigated children. No significant differences in serum homocysteine concentration were observed between the investigated groups. However, its concentration was significantly higher in children with two atherosclerosis risk factors. No significant differences in expression of s-VCAM-1 were observed in the investigated groups, concentration of sP-selectin was significantly higher in children with atherosclerosis risk factors (phomocysteine and chosen adhesion molecules in children with atherosclerosis risk factors might potentially constitute the marker of early

  15. Exercise-induced changes in stress hormones and cell adhesion molecules in obese men

    Directory of Open Access Journals (Sweden)

    Park J

    2018-03-01

    Full Text Available Jinkyung Park,1 Darryn S Willoughby,2 Joon Jin Song,3 Brian C Leutholtz,2 Yunsuk Koh2 1Department of Kinesiology, George Mason University, Manassas, VA, USA; 2Department of Health, Human Performance, Recreation, Baylor University, Waco, TX, USA; 3Department of Statistical Science, Baylor University, Waco, TX, USA Purpose: The current study examined the relationship between exercise-induced changes in stress hormones (epinephrine, norepinephrine, and cortisol and vascular inflammatory markers (soluble intracellular adhesion molecule-1 [sICAM-1], soluble endothelial selectin [sE-selectin], and soluble vascular adhesion molecule-1 [sVCAM-1] in obese men over a 24-hour period following exercise at lower and higher intensity.Patients and methods: Fifteen physically inactive, obese, college-aged men performed a single bout of cycling exercise at lower and higher intensities (lower intensity: 50% of maximal heart rate, and higher intensity: 80% of maximal heart rate in random order. Overnight fasting blood samples were collected at baseline, immediately postexercise (IPE, 1-hour PE (1-h PE, and 24-hour PE. Changes in stress hormones and inflammatory markers were analyzed with a repeated-measures analysis of variance using Bonferroni multiple comparisons and a linear regression analysis (p<0.05.Results: sICAM-1, sVCAM-1, epinephrine, and norepinephrine did not change over time, while sE-selectin was significantly lower at 1-h PE (10.25±1.07 ng/mL, p=0.04 than at baseline (12.22±1.39 ng/mL. Cortisol and sICAM-1 were negatively related at 1-h PE following lower-intensity exercise (r2=0.34, p=0.02, whereas cortisol and sVCAM-1 were positively related at IPE following higher-intensity exercise (r2=0.36, p=0.02.Conclusion: Regardless of intensity, an acute bout of aerobic exercise may lower sE-selectin in sedentary obese men. Responses of cortisol are dependent on exercise intensity, and cortisol may be a key stress hormone playing a major role in

  16. Alterations of epithelial adhesion molecules and basement membrane components in lattice corneal dystrophy (LCD).

    Science.gov (United States)

    Resch, Miklós D; Schlötzer-Schrehardt, Ursula; Hofmann-Rummelt, Carmen; Kruse, Friedrich E; Seitz, Berthold

    2009-08-01

    The aim of the study was to investigate the histopathological and ultrastructural correlate of delayed epithelial healing in eyes with lattice corneal dystrophy (LCD). Corneal buttons from 4 patients with LCD (two with subepithelial, two with stromal amyloid deposits) and 2 control corneas were examined. Cell-matrix adhesion molecules and basement membrane components of the corneal epithelium were analyzed by immunohistochemistry and hemidesmosomes between epithelium and stroma were quantified by transmission electron microscopy (TEM). By TEM well-developed hemidesmosomes anchored the basal epithelial cells to the underlying basement membrane in all normal and LCD corneas. Hemidesmosome density was not significantly different in subepithelial (224.7 +/- 34.1/100 microm) and stromal (234.3 +/- 36.3/100 microm) LCD compared to controls (241.3 +/- 26.8/100 microm). The basement membrane was interrupted in subepithelial, but continuous in stromal LCD. Integrin alpha6 and beta4 staining formed a continuous line along the basal surface of the corneal epithelium in control corneas, whereas it appeared discontinuous and patchy both in subepithelial and stromal forms of LCD. Staining for alphaV integrin showed irregular staining patterns, i.e. enhanced labelling intensity in subepithelial and interrupted pattern in stromal LCD, respectively. Integrins alpha3, beta1, beta2, and beta5, dystroglycan, and plectin were not markedly different in dystrophic corneas. Type VII collagen showed a discontinuous staining in subepithelial forms of LCD. In stromal forms of LCD, type VII collagen staining occurred in additional patches underneath the epithelial basement membrane zone. Type XVII collagen staining was reduced in subepithelial LCD. Laminin-1, laminin-5 and laminin gamma2 showed variable irregular staining patterns in dystrophic corneas with focal interruptions, focal thickenings, and reduplications of basement membrane. Some irregularities in corneas with subepithelial

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

  18. Upregulation of adhesion molecules on leukemia targets improves the efficacy of cytotoxic T cells transduced with chimeric anti-CD19 receptor.

    Science.gov (United States)

    Laurin, David; Marin, Virna; Biagi, Ettore; Pizzitola, Irene; Agostoni, Valentina; Gallot, Géraldine; Vié, Henri; Jacob, Marie Christine; Chaperot, Laurence; Aspord, Caroline; Plumas, Joël

    2013-04-01

    T lymphocytes engineered to express chimeric antigen receptors (CARs) interact directly with cell surface molecules, bypassing MHC antigen presentation dependence. We generated human anti-CD19ζ CAR cytotoxic T lymphocytes and cytokine-induced killer cells and studied their sensitivity to the expression of adhesion molecules for the killing of primary B-lineage acute lymphoblastic leukemia (B-ALL) targets. Despite a very low basal expression of surface adhesion molecules, B-ALL blasts were lysed by the anti-CD19ζ-CAR transduced effectors as expected. We next investigated the regulatory role of adhesion molecules during CAR-mediated cytolysis. The blocking of these accessory molecules strongly limited the chimeric effector's cytotoxicity. Thereafter, B-ALL cells surface adhesion molecule level expression was induced by IFN-γ or by the combined use of CD40L and IL-4 and the cells were submitted to anti-CD19ζ-CAR transduced effectors lysis. Upregulation of adhesion molecules expression by blasts potentiated their killing. The improved cytotoxicity observed was dependent on target surface expression of adhesion molecules, particularly CD54. Taken together, these results indicate that adhesion molecules, and principally CD54, are involved in the efficiency of recognition by effector chimeric ζ. These observations have potential implications for the design of immunotherapy treatment approaches for hematological malignancies and tumors based on the adoption of CAR effector cells.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Gene expression profiles of cell adhesion molecules, matrix metalloproteinases and their tissue inhibitors in canine oral tumors.

    Science.gov (United States)

    Pisamai, Sirinun; Rungsipipat, Anudep; Kalpravidh, Chanin; Suriyaphol, Gunnaporn

    2017-08-01

    Perturbation of cell adhesion can be essential for tumor cell invasion and metastasis, but the current knowledge on the gene expression of molecules that mediate cell adhesion in canine oral tumors is limited. The present study aimed to investigate changes in the gene expression of cell adhesion molecules (E-cadherin or CDH1, syndecan 1 or SDC1, NECTIN2 and NECTIN4), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), in canine oral tumors, including benign tumors, oral melanoma (OM) and non-tonsillar oral squamous cell carcinoma (OSCC), by quantitative real-time reverse transcription PCR. When compared with the normal gingival controls, decreased CDH1, SDC1 and NECTIN4 expression levels were observed in OSCC and OM, reflecting a possible role as cell adhesion molecules and tumor suppressors in canine oral cancers in contrast to the upregulation of MMP2 expression. Downregulated MMP7 was specifically revealed in the OM group. In the late-stage OM, the positive correlation of MMP7 and CDH1 expression was noticed as well as that of SDC1 and NECTIN4. Enhanced TIMP1 expression was shown in all tumor groups with prominent expression in the benign tumors and the early-stage OM. MMP14 expression was notable in the early-stage OM. Higher MMP9 and TIMP1 expression was observed in the acanthomatous ameloblastoma. In conclusion, this study revealed that the altered expression of cell adhesion molecules, MMP7 and MMP2 was correlated with clinicopathologic features in canine oral cancers whereas TIMP1 and MMP14 expression was probably associated with early-stage tumors; therefore, these genes might serve as molecular markers for canine oral tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Millers, A.; Enina, G.; Platkajis, A.; Metra, M.; Kukaine, R.

    2002-01-01

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

  2. The Multivalent Adhesion Molecule SSO1327 plays a key role in Shigella sonnei pathogenesis.

    Science.gov (United States)

    Mahmoud, Rasha Y; Stones, Daniel Henry; Li, Wenqin; Emara, Mohamed; El-Domany, Ramadan A; Wang, Depu; Wang, Yili; Krachler, Anne Marie; Yu, Jun

    2016-02-01

    Shigella sonnei is a bacterial pathogen and causative agent of bacillary dysentery. It deploys a type III secretion system to inject effector proteins into host epithelial cells and macrophages, an essential step for tissue invasion and immune evasion. Although the arsenal of bacterial effectors and their cellular targets have been studied extensively, little is known about the prerequisites for deployment of type III secreted proteins during infection. Here, we describe a novel S. sonnei adhesin, SSO1327 which is a multivalent adhesion molecule (MAM) required for invasion of epithelial cells and macrophages and for infection in vivo. The S. sonnei MAM mediates intimate attachment to host cells, which is required for efficient translocation of type III effectors into host cells. SSO1327 is non-redundant to IcsA; its activity is independent of type III secretion. In contrast to the up-regulation of IcsA-dependent and independent attachment and invasion by deoxycholate in Shigella flexneri, deoxycholate negatively regulates IcsA and MAM in S. sonnei resulting in reduction in attachment and invasion and virulence attenuation in vivo. A strain deficient for SSO1327 is avirulent in vivo, but still elicits a host immune response. © 2015 John Wiley & Sons Ltd.

  3. Down syndrome cell adhesion molecule 1: testing for a role in insect immunity, behaviour and reproduction.

    Science.gov (United States)

    Peuß, Robert; Wensing, Kristina U; Woestmann, Luisa; Eggert, Hendrik; Milutinović, Barbara; Sroka, Marlene G U; Scharsack, Jörn P; Kurtz, Joachim; Armitage, Sophie A O

    2016-04-01

    Down syndrome cell adhesion molecule 1 (Dscam1) has wide-reaching and vital neuronal functions although the role it plays in insect and crustacean immunity is less well understood. In this study, we combine different approaches to understand the roles that Dscam1 plays in fitness-related contexts in two model insect species. Contrary to our expectations, we found no short-term modulation of Dscam1 gene expression after haemocoelic or oral bacterial exposure in Tribolium castaneum, or after haemocoelic bacterial exposure in Drosophila melanogaster. Furthermore, RNAi-mediated Dscam1 knockdown and subsequent bacterial exposure did not reduce T. castaneum survival. However, Dscam1 knockdown in larvae resulted in adult locomotion defects, as well as dramatically reduced fecundity in males and females. We suggest that Dscam1 does not always play a straightforward role in immunity, but strongly influences behaviour and fecundity. This study takes a step towards understanding more about the role of this intriguing gene from different phenotypic perspectives.

  4. CHLORHEXIDINE INHIBITS L1 CELL ADHESION MOLECULE MEDIATED NEURITE OUTGROWTH IN VITRO

    Science.gov (United States)

    Milstone, Aaron M.; Bamford, Penny; Aucott, Susan W.; Tang, Ningfeng; White, Kimberly R.; Bearer, Cynthia F.

    2013-01-01

    Background Chlorhexidine is a skin disinfectant that reduces skin and mucous membrane bacterial colonization and inhibits organism growth. Despite numerous studies assessing chlorhexidine safety in term infants, residual concerns have limited its use in hospitalized neonates, especially low birth weight preterm infants. The aim of this study was to assess the potential neurotoxicity of chlorhexidine on the developing central nervous system using a well-established in vitro model of neurite outgrowth that includes laminin and L1 cell adhesion molecule (L1) as neurite outgrowth promoting substrates. Methods Cerebellar granule neurons are plated on either poly L-lysine, L1 or laminin. Chlorhexidine, hexachlorophene or their excipients are added to the media. Neurons are grown for 24 h, then fixed and neurite length measured. Results Chlorhexidine significantly reduced the length of neurites grown on L1 but not laminin. Chlorhexidine concentrations as low as 125 ng/ml statistically significantly reduced neurite length on L1. Hexachlorophene did not affect neurite length. Conclusion Chlorhexidine at concentrations detected in the blood following topical applications in preterm infants specifically inhibited L1 mediated neurite outgrowth of cerebellar granule neurons. It is now vital to determine whether the blood brain barrier is permeable to chlorhexidine in preterm infants. PMID:24126818

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

    International Nuclear Information System (INIS)

    El-Shepiny, M.S.E.M.

    2013-01-01

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

  6. Adhesion Regulating Molecule 1 Mediates HAP40 Overexpression-Induced Mitochondrial Defects

    Science.gov (United States)

    Huang, Zih-Ning; Chung, Her Min; Fang, Su-Chiung; Her, Lu-Shiun

    2017-01-01

    Striatal neuron death in Huntington's disease is associated with abnormal mitochondrial dynamics and functions. However, the mechanisms for this mitochondrial dysregulation remain elusive. Increased accumulation of Huntingtin-associated protein 40 (HAP40) has been shown to be associated with Huntington's disease. However, the link between increased HAP40 and Huntington's disease remains largely unknown. Here we show that HAP40 overexpression causes mitochondrial dysfunction and reduces cell viability in the immortalized mouse striatal neurons. HAP40-associated mitochondrial dysfunction is associated with reduction of adhesion regulating molecule 1 (ADRM1) protein. Consistently, depletion of ADRM1 by shRNAs impaired mitochondrial functions and increased mitochondrial fragmentation in mouse striatal cells. Moreover, reducing ADRM1 levels enhanced activity of fission factor dynamin-related GTPase protein 1 (Drp1) via increased phosphorylation at serine 616 of Drp1 (Drp1Ser616). Restoring ADRM1 protein levels was able to reduce HAP40-induced ROS levels and mitochondrial fragmentation and improved mitochondrial functions and cell viability. Moreover, reducing Drp1 activity by Drp1 inhibitor, Mdivi-1, ameliorates both HAP40 overexpression- and ADRM1 depletion-induced mitochondrial dysfunction. Taken together, our studies suggest that HAP40-mediated reduction of ADRM1 alters the mitochondrial fission activity and results in mitochondrial fragmentation and mitochondrial dysfunction. PMID:29209146

  7. 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.

  8. In vitro and in situ intercellular adhesion molecule-1 (ICAM-1) expression by endothelial cells lining a polyester fabric.

    Science.gov (United States)

    Rémy, M; Valli, N; Brethes, D; Labrugère, C; Porté-Durrieu, M C; Dobrova, N B; Novikova, S P; Gorodkov, A J; Bordenave, L

    1999-02-01

    In order to improve long-term patency of vascular grafts, the promising concept of endothelial cell seeding is actually under investigation. Our laboratory tested a polyester coated with albumin and chitosan which permits a rapid colonization by human umbilical vein endothelial cells (HUVEC) and it seems relevant to test in vitro the expression of adhesive molecules expressed by cells with regard to the inflammatory process. We studied intercellular adhesion molecule-1 (ICAM-1) expression and focused our work on the determination of ICAM-1 sites expressed per adherent cell lining the biomaterial, thus in situ, in comparison to control HUVEC on plastic wells: the results obtained by binding experiments were correlated to flow cytometry analyses and showed that the polyester does not induce a proinflammatory state and that HUVEC covering the structure are able to respond to a stimulus.

  9. 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

    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...... 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...

  10. 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

  11. Short-term effects of Mediterranean-type diet intervention on soluble cellular adhesion molecules in subjects with abdominal obesity.

    Science.gov (United States)

    Rallidis, Loukianos S; Kolomvotsou, Anastasia; Lekakis, John; Farajian, Paul; Vamvakou, Georgia; Dagres, Nikolaos; Zolindaki, Maria; Efstathiou, Stamatis; Anastasiou-Nana, Maria; Zampelas, Antonis

    2017-02-01

    Abdominal obesity (AO) is associated with increased risk for cardiovascular disease and with increased production of adhesion molecules. The present work examined the effect of a Mediterranean-style diet on soluble cellular adhesion molecules in individuals with AO. Ninety subjects with AO without cardiovascular disease or diabetes mellitus were randomly allocated to the intervention or control group and were instructed to follow a Mediterranean-style diet for two months. Intervention group followed a specific relevant food plan with close dietetic supervision and provision of basic foods. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), sP and sE-selectin, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. Subjects in the intervention group increased their intake of total fat, monounsaturated fatty acids, dietary fiber, vitamin C, and alcohol compared to controls, while decreased their intake of saturated fat. Although there was a significant decrease in CRP, sP-selectin and in sE-selectin in the intervention group, and an increase in sVCAM-1 in the control group, between-group analysis showed no statistically significant differences. There were also no significant changes in sICAM-1, and IL-6 levels after intervention. Mediterranean-type diet for two months combined with close dietetic supervision showed a beneficial tendency towards the down-regulation of some markers of vascular inflammation, although the comparison between groups after the intervention did not reach statistical significance. A longer period of dietary intervention may be required to further support these changes. Copyright © 2016. Published by Elsevier Ltd.

  12. Chlorella 11-Peptide Inhibits the Production of Macrophage-Induced Adhesion Molecules and Reduces Endothelin-1 Expression and Endothelial Permeability

    Science.gov (United States)

    Shih, Mei Fen; Chen, Lih Chi; Cherng, Jong Yuh

    2013-01-01

    The inflammation process in large vessels involves the up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are also known as the markers of atherosclerosis. We have reported that Chlorella 11-peptide exhibited effective anti-inflammatory effects. This peptide with an amino sequence Val-Glu-Cys-Tyr-Gly-Pro-Asn-Arg-Pro-Gln-Phe was further examined for its potential in preventing atherosclerosis in this study. In particular, the roles of Chlorella 11-peptide in lowering the production of vascular adhesion molecules, monocyte chemoattractant protein (MCP-1) and expression of endothelin-1 (ET-1) from endothelia (SVEC4-10 cells) were studied. The production of E-selectin, ICAM-1, VCAM-1 and MCP-1 in SVEC4-10 cells was measured with ELISA. The mRNA expression of ET-1 was analyzed by RT-PCR and agarose gel. Results showed that Chlorella 11-peptide significantly suppressed the levels of E-selectin, ICAM, VCAM, MCP-1 as well as ET-1 gene expression. The inhibition of ICAM-1 and VCAM-1 production by Chlorella 11-peptide was reversed in the presence of protein kinase A inhibitor (H89) which suggests that the cAMP pathway was involved in the inhibitory cause of the peptide. In addition, this peptide was shown to reduce the extent of increased intercellular permeability induced by combination of 50% of lipopolysaccharide (LPS)-activated RAW 264.7 cells medium and 50% normal SEVC cell culture medium (referred to as 50% RAW-conditioned medium). These data demonstrate that Chlorella 11-peptide is a promising biomolecule in preventing chronic inflammatory-related vascular diseases. PMID:24129228

  13. The intercellular cell adhesion molecule-1 (icam-1) in lung cancer: implications for disease progression and prognosis.

    Science.gov (United States)

    Kotteas, Elias A; Boulas, Panagiotis; Gkiozos, Ioannis; Tsagkouli, Sofia; Tsoukalas, George; Syrigos, Konstantinos N

    2014-09-01

    The intercellular cell-adhesion molecule-1 (ICAM-1) is a transmembrane molecule and a distinguished member of the Immunoglobulin superfamily of proteins that participates in many important processes, including leukocyte endothelial transmigration, cell signaling, cell-cell interaction, cell polarity and tissue stability. ICAM-1and its soluble part are highly expressed in inflammatory conditions, chronic diseases and a number of malignancies. In the present article we present the implications of ICAM-1 in the progression and prognosis of one of the major global killers of our era: lung cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Exogenous, but not Endogenous Nitric Oxide Inhibits Adhesion Molecule Expression in Human Endothelial Cells

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    Jin eQian

    2012-01-01

    Full Text Available Nitric oxide (NO has many beneficial actions on the vascular wall including suppression of inflammation. The mechanism(s by which NO antagonizes cytokine signaling are poorly understood, but are thought to involve inhibition of the pro-inflammatory transcription factor, NF-κB. NO represses nuclear translocation of NF-κB via the S-nitrosylation of its subunits which decreases the expression of target genes including adhesion molecules. In previous studies, we have shown that the intracellular location of endothelial nitric oxide synthase (eNOS can influence the amount of NO produced and that NO levels are paramount in regulating the S-nitrosylation of target proteins. The purpose of the current study was to investigate the significance of subcellular eNOS to NF-κB signaling induced by proinflammatory cytokines in human aortic endothelial cells (HAECs. We found that in HAECs stimulated with TNFα, L-NAME did not influence the expression of ICAM-1 or VCAM-1. In eNOS knock down HAECs reconstituted with either plasma membrane or Golgi restricted forms of eNOS, there was no significant effect on the activation of the NF-κB pathway over different times and concentrations of TNFα. Similarly, the endogenous production of NO did not influence the phosphorylation of IkBα. In contrast, higher concentrations of NO derived from the use of the exogenous NO donor, DETA NONOate, effectively suppressed the expression of ICAM-1/VCAM-1 in response to TNFα. Collectively these results suggest that neither endogenous eNOS nor eNOS location is an important influence on inflammatory signaling via the NF-κB pathway and that higher NO concentrations are required to suppress NF-κB in HAECs.

  15. Changes in some Blood Micronutrients, Leukocytes and Neutrophil Expression of Adhesion Molecules in Periparturient Dairy Cows

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    Petersson L

    2001-03-01

    Full Text Available Dairy cows are highly susceptible to infectious diseases, like mastitis, during the period around calving. Although factors contributing to increased susceptibility to infection have not been fully elucidated, impaired neutrophil recruitment to the site of infection and changes in the concentrations of some micronutrients related with the function of the immune defence has been implicated. Most of the current information is based on studies outside the Nordic countries where the conditions for dairy cows are different. Therefore, the aim of the study was to evaluate changes in blood concentrations of the vitamins A and E, the minerals calcium (Ca, phosphorous (P, and magnesium (Mg, the electrolytes potassium (K and sodium (Na and the trace elements selenium (Se, copper (Cu and zinc (Zn, as well as changes in total and differential white blood cell counts (WBC and expression of the adhesion molecules CD62L and CD18 on blood neutrophils in Swedish dairy cows during the period around calving. Blood samples were taken from 10 cows one month before expected calving, at calving and one month after calving. The results were mainly in line with reports from other countries. The concentrations of vitamins A and E, and of Zn, Ca and P decreased significantly at calving, while Se, Cu, and Na increased. Leukocytosis was detected at calving, mainly explained by neutrophilia, but also by monocytosis. The numbers of lymphocytes tended to decrease at the same time. The mean fluorescent intensity (MFI of CD62L and CD18 molecules on blood neutrophils remained constant over time. The proportion of CD62L+ neutrophils decreased significantly at calving. The animals were fed according to, or above, their requirements. Therefore, changes in blood levels of vitamins, minerals and trace elements were mainly in response to colostrum formation, changes in dry matter intake, and ruminal metabolism around calving. Decreased levels of vitamins A and E, and of Zn at calving

  16. 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.

  17. Increased fluidity and oxidation of malarial lipoproteins: relation with severity and induction of endothelial expression of adhesion molecules

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    Looareesuwan Sornchai

    2004-06-01

    Full Text Available Abstract Introduction Oxidative stress has been demonstrated in malaria. The potential oxidative modification of lipoproteins derived from malaria patients was studied. These oxidized lipids may have role in pathogenesis of malaria. Method The plasma lipid profile and existence of oxidized forms of very low density lipoprotein (VLDL, low density lipoprotein (LDL and high density lipoprotein (HDL were investigated in malaria (17 mild and 24 severe patients and 37 control subjects. Thiobarbituric acid reactive substances (TBARs, conjugated dienes, tryptophan fluorescence and fluidity of lipoproteins were determined as markers of oxidation. The biological effect of malarial lipoproteins was assessed by the expression of adhesion molecules on endothelial cells. Results Malarial lipoproteins had decreased cholesterol (except in VLDL and phospholipid. The triglyceride levels were unchanged. The cholesterol/phospholipid ratio of LDL was decreased in malaria, but increased in VLDL and HDL. TBARs and conjugate dienes were increased in malarial lipoproteins, while the tryptophan fluorescence was decreased. The fluidity of lipoproteins was increased in malaria. These indicated the presence of oxidized lipoproteins in malaria by which the degree of oxidation was correlated with severity. Of three lipoproteins from malarial patients, LDL displayed the most pronounced oxidative modification. In addition, oxidized LDL from malaria patients increased endothelial expression of adhesion molecules. Conclusion In malaria, the lipoproteins are oxidatively modified, and the degree of oxidation is related with severity. Oxidized LDL from malarial patients increases the endothelial expression of adhesion molecules. These suggest the role of oxidized lipoproteins, especially LDL, on the pathogenesis of disease.

  18. Sarcoptes scabiei (Acari: Sarcoptidae) mite extract modulates expression of cytokines and adhesion molecules by human dermal microvascular endothelial cells.

    Science.gov (United States)

    Elder, B Laurel; Arlian, Larry G; Morgan, Marjorie S

    2006-09-01

    The inflammatory and immune responses seen with the worldwide disease scabies, caused by the mite Sarcoptes scabiei (De Geer) (Acari: Sarcoptidae), are complex. Clinical symptoms are delayed for weeks in patients when they are infested with scabies for the first time. This study was undertaken to elucidate the role of the human dermal microvascular endothelial cell (HMVEC-D) in modulating the inflammatory and immune responses in the skin to S. scabiei. Extracts of S. scabiei were incubated with HMVEC-D and the expression of adhesion molecules and chemokine receptors on the cells and the secretion of selected cytokines were determined by enzyme-linked immunosorbent assay. S. scabiei extract was found to inhibit HMVEC-D expression of E-selectin and vascular cell adhesion molecule-1, although not intercellular adhesion molecule-1. The secretion of interleukin-8 also was inhibited by S. scabiei extract. S. scabiei extract increased expression of the chemokine receptor CXCR-1 and both down-regulated and up-regulated expression of CXCR-2, depending on the concentration tested. These findings help explain the delayed inflammatory reaction to infestation with S. scabiei.

  19. 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.

  20. 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 cells...... were exposed to primary nanoparticles (fine, photocatalytic or nanosized TiO(2), aluminium silicate, carbon black, nano-silicasol or axilate) and dust from sanding reference- or nanoparticle-containing paints. Most of the samples increased cell surface expressions of vascular cell adhesion molecule-1...... (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), but paint sanding dust samples generally generated less response than primary particles of TiO(2) and carbon black. We found no relationship between the expression of adhesion molecules, cytotoxicity and production of reactive oxygen species...

  1. Arsenite enhances tumor necrosis factor-α-induced expression of vascular cell adhesion molecule-1

    International Nuclear Information System (INIS)

    Tsou, T.-C.; Yeh, Szu Ching; Tsai, E.-M.; Tsai, F.-Y.; Chao, H.-R.; Chang, Louis W.

    2005-01-01

    Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-α (TNF-α), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-α-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-κB (NF-κB). To elucidate the role of GSH in regulation of AP-1, NF-κB, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific γ-glutamylcysteine synthetase (γ-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-α-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-κB activations by TNF-α. Moreover, we found that depletion of GSH would also attenuate the TNF-α-induced VCAM-1 expression with a down-regulation of the TNF-α-induced NF-κB activation and without significant effect on AP-1. On the other hand, the TNF-α-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-κB activity, suggesting that activation of both AP-1 and NF-κB was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-α-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-κB activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions of proinflammatory cytokines

  2. L-Cysteine in vitro can restore cellular glutathione and inhibits the expression of cell adhesion molecules in G6PD-deficient monocytes.

    Science.gov (United States)

    Parsanathan, Rajesh; Jain, Sushil K

    2018-04-06

    L-Cysteine is a precursor of glutathione (GSH), a potent physiological antioxidant. Excess glucose-6-phosphate dehydrogenase (G6PD) deficiency in African Americans and low levels of L-cysteine diet in Hispanics can contributes to GSH deficiency and oxidative stress. Oxidative stress and monocyte adhesion was considered to be an initial event in the progression of vascular dysfunction and atherosclerosis. However, no previous study has investigated the contribution of GSH/G6PD deficiency to the expression of monocyte adhesion molecules. Using human U937 monocytes, this study examined the effect of GSH/G6PD deficiency and L-cysteine supplementation on monocyte adhesion molecules. G6PD/GSH deficiency induced by either siRNA or inhibitors (6AN/BSO, respectively) significantly (p adhesion molecules (ICAM-1, VCAM-1, SELL, ITGB1 and 2); NADPH oxidase (NOX), reactive oxygen species (ROS) and MCP-1 were upregulated, and decreases in levels of GSH, and nitric oxide were observed. The expression of ICAM-1 and VCAM-1 mRNA levels increased in high glucose, MCP-1 or TNF-α-treated G6PD-deficient compared to G6PD-normal cells. L-Cysteine treatment significantly (p adhesion molecules. Thus, GSH/G6PD deficiency increases susceptibility to monocyte adhesion processes, whereas L-cysteine supplementation can restore cellular GSH/G6PD and attenuates NOX activity and expression of cell adhesion molecules.

  3. Correlation of body mass index with Th1/Th2 balance, adhesion molecules and insulin signal transduction in infertile patients

    Directory of Open Access Journals (Sweden)

    Hui-Juan Zhang

    2017-11-01

    Full Text Available Objective: To study the correlation of body mass index with Th1/Th2 balance, adhesion molecules and insulin signal transduction in infertile patients. Methods: A total of 132 patients who received diagnostic curettage due to infertility in Tangshan Maternal and Child Health Hospital between June 2015 and March 2016 were selected as the research subjects and divided into the normal group with BMI 30 kg/m 2 according to BMI, and the levels of Th1/ Th2 cytokines in serum as well as the expression of Th1/Th2 transcription factors, adhesion molecules and insulin signal pathway molecules in endometrial tissue were detected. Results: IFN-γ and TNF-α levels in serum of obesity group and overweight group were significantly higher than those of control group while IL-4, IL-5 and IL-13 levels in serum as well as CD44V6, N-cadherin, FAK, ICAM-1, GLUT-4, IRS-1, PI3K and AKT mRNA expression in endometrial tissue were significantly lower than those of control group; IFN-γ and TNF-α levels in serum of obesity group were significantly higher than those of overweight group while IL-4, IL-5 and IL-13 levels in serum as well as CD44V6, N-cadherin, FAK, ICAM-1, GLUT-4, IRS-1, PI3K and AKT mRNA expression in endometrial tissue were significantly lower than those of overweight group. Conclusion: Weight gain can aggravate the Th1/Th2 disorder, reduce the adhesion molecule expression and hinder the insulin signal transduction in infertile patients.

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

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    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

  5. Cell adhesion molecules in the development of inflammatory infiltrates in giant cell arteritis: inflammation-induced angiogenesis as the preferential site of leukocyte-endothelial cell interactions.

    Science.gov (United States)

    Cid, M C; Cebrián, M; Font, C; Coll-Vinent, B; Hernández-Rodríguez, J; Esparza, J; Urbano-Márquez, A; Grau, J M

    2000-01-01

    To investigate the expression pattern of adhesion molecules involved in leukocyte-endothelial cell interactions in giant cell arteritis (GCA). Immunohistochemical analysis was performed on frozen temporal artery sections from 32 patients with biopsy-proven GCA and from 12 control patients with other diseases. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), very late activation antigen 4 (VLA-4), Mac-1 (CD18/CD11b), and gp 150,95 (CD18/CD11c). Clinical and biochemical parameters of inflammation in the patients, as well as the duration of previous corticosteroid treatment, were prospectively recorded. Constitutive (PECAM-1, ICAM-1, ICAM-2, and P-selectin) and inducible (E-selectin and VCAM-1) endothelial adhesion molecules for leukocytes were mainly expressed by adventitial microvessels and neovessels within inflammatory infiltrates. Concurrent analysis of leukocyte receptors indicated a preferential use of VLA-4/VCAM-1 and LFA-1/ICAM-1 at the adventitia and Mac-1/ICAM-1 at the intima-media junction. The intensity of inducible endothelial adhesion molecule expression (E-selectin and VCAM-1) correlated with the intensity of the systemic inflammatory response. Previous corticosteroid treatment reduced, but did not completely abrogate, the expression of the inducible endothelial adhesion molecules E-selectin and VCAM-1. Inflammation-induced angiogenesis is the main site of leukocyte-endothelial cell interactions leading to the development of inflammatory infiltrates in GCA. The distribution of leukocyte-endothelial cell ligand pairs suggests a heterogeneity in leukocyte-endothelial cell interactions used by different functional cell subsets at distinct areas of the temporal artery.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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 α 2 , integrin α 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.

  7. 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.

  8. 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.

  9. Exosomes from iPSCs Delivering siRNA Attenuate Intracellular Adhesion Molecule-1 Expression and Neutrophils Adhesion in Pulmonary Microvascular Endothelial Cells.

    Science.gov (United States)

    Ju, Zhihai; Ma, Jinhui; Wang, Chen; Yu, Jie; Qiao, Yeru; Hei, Feilong

    2017-04-01

    The pro-inflammatory activation of pulmonary microvascular endothelial cells resulting in continuous expression of cellular adhesion molecules, and subsequently recruiting primed neutrophils to form a firm neutrophils-endothelium (PMN-EC) adhesion, has been examined and found to play a vital role in acute lung injury (ALI). RNA interference (RNAi) is a cellular process through harnessing a natural pathway silencing target gene based on recognition and subsequent degradation of specific mRNA sequences. It opens a promising approach for precision medicine. However, this application was hampered by many obstacles, such as immunogenicity, instability, toxicity problems, and difficulty in across the biological membrane. In this study, we reprogrammed urine exfoliated renal epithelial cells into human induced pluripotent stem cells (huiPSCs) and purified the exosomes (Exo) from huiPSCs as RNAi delivery system. Through choosing the episomal system to deliver transcription factors, we obtained a non-integrating huiPSCs. Experiments in both vitro and vivo demonstrated that these huiPSCs possess the pluripotent properties. The exosomes of huiPSCs isolated by differential centrifugation were visualized by transmission electron microscopy (TEM) showing a typical exosomal appearance with an average diameter of 122 nm. Immunoblotting confirmed the presence of the typical exosomal markers, including CD63, TSG 101, and Alix. Co-cultured PKH26-labeled exosomes with human primary pulmonary microvascular endothelial cells (HMVECs) confirmed that they could be internalized by recipient cells at a time-dependent manner. Then, electroporation was used to introduce siRNA against intercellular adhesion molecule-1 (ICAM-1) into exosomes to form an Exo/siRNA compound. The Exo/siRNA compound efficiently delivered the target siRNA into HMVECs causing selective gene silencing, inhibiting the ICAM-1 protein expression, and PMN-EC adhesion induced by lipopolysaccharide (LPS). These data suggest

  10. 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.

  11. Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial.

    Science.gov (United States)

    Sacanella, Emilio; Vázquez-Agell, Mònica; Mena, Mari Pau; Antúnez, Emilia; Fernández-Solá, Joaquim; Nicolás, José Maria; Lamuela-Raventós, Rosa M; Ros, Emilio; Estruch, Ramón

    2007-11-01

    Moderate alcohol consumption is cardioprotective. The mechanism for this beneficial effect might be reduced inflammatory responses, as suggested by prospective studies and small clinical trials in men. No studies have evaluated the antiinflammatory effects of wine in women. We investigated whether low-dose intake of white and red wines has differential effects on inflammatory markers in women. In a crossover study, we randomly assigned 35 healthy women to two 4-wk periods of 20 g ethanol/d as white or red wine, preceded by two 4-wk washout periods. Before and after interventions, we measured serum lipids, circulating inflammatory biomarkers, cellular adhesion molecules (CAMs), and adhesion of monocytes to stimulated endothelial cells. HDL cholesterol increased, and the serum concentrations of high-sensitivity C-reactive protein, intercellular adhesion molecule-1, CD40L, and interleukin-6 decreased after either wine (P < 0.01, all). Vascular CAM-1 and E-selectin decreased (P < 0.01) only after red wine. CAM expression by mononuclear cells was blunted after either wine, with a greater suppressant effect of red wine. Enhanced adhesion of monocytes to stimulated endothelial cells was reduced by 51% (95% CI: -57%, -45%) after white wine and by 89% (95% CI: -96%, -82%) after red wine (P = 0.01 for between-wine differences). Moderate wine consumption is associated with beneficial effects on various inflammatory pathways related to endothelial activation in women. Probably because of its higher polyphenol content, red wine shows superior antiinflammatory effects than does white wine. Reducing low-grade inflammation and endothelial activation may be another potential mechanism by which alcoholic beverages exert their cardioprotective effect.

  12. 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.

  13. Differential effect of prostaglandins E1 and E2 on lipopolysaccharide-induced adhesion molecule expression on human monocytes.

    Science.gov (United States)

    Takahashi, Hideo K; Iwagaki, Hiromi; Tamura, Ryuji; Katsuno, Goutaro; Xue, Dong; Sugita, Sachi; Mori, Shuji; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro

    2005-04-11

    The effect of prostaglandins E1 and E2 on the 1 ng/ml lipopolysaccharide-induced expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes was examined. Prostaglandin E1 suppressed B7.1 and CD40 expression, but prostaglandin E2 did not effect on any type of adhesion molecule expression. Both prostaglandins inhibited tumor necrosis factor (TNF)-alpha production and T-cell proliferation of lipopolysaccharide-treated human peripheral blood mononuclear cells (PBMC). Among prostaglandin E1 receptors (IP/EP1/EP2/EP3/EP4) agonists, ONO-1301, a prostanoid IP-receptor agonist, prevented B7.1 and CD40 expression. ONO-AE1-259-01 a prostanoid EP2-receptor agonist, ONO-AE1-329, a prostanoid EP4-receptor agonist, and ONO-1301 inhibited TNF-alpha production and T-cell proliferation. Moreover, anti-B7.1 and anti-CD40 Abs prevented lipopolysaccharide-induced TNF-alpha production and T-cell proliferation. Therefore, the effect of prostaglandin E1 on TNF-alpha production and T-cell proliferation might depend on the inhibition of B7.1 and CD40 expression, but that of prostaglandin E2 might be independent of adhesion molecules expression. In conclusion, the mechanism responsible for the effect of prostaglandin E1 on lipopolysaccharide-induced responses is distinct from that of prostaglandin E2.

  14. Crevicular fluid levels of interleukin-8, interleukin-17 and soluble intercellular adhesion molecule-1 after regenerative periodontal therapy.

    Science.gov (United States)

    Erdemir, Ebru Olgun; Hendek, Meltem Karsiyaka; Keceli, H Gencay; Apan, Teoman Z

    2015-01-01

    The aim of this study is to evaluate the influence of regenerative periodontal therapy on clinical parameters and interleukin-8 (IL-8), IL-17 and soluble intercellular adhesion molecule-1 (sICAM-1) levels in gingival crevicular fluid (GCF) of subjects with chronic periodontitis (CP). Fifteen patients received demineralized freeze-dried bone allograft (DFDBA) surgically to the site of infrabony defect. Clinical periodontal indices were recorded, and GCF samples were collected at baseline and at the 6(th) and the 9(th) month after the surgery. Except plaque index, all clinical parameters improved following surgery (P periodontal healing after demineralized freeze-dried bone grafting.

  15. 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.

  16. Changes of Serum Intercellular Adhesion Molecule – 1, Vascular Adhesion Molecule-1 and C – Reactive Protein in Middle-Aged Men with Heart Failure after Eight Weeks of Aerobic Exercise

    Directory of Open Access Journals (Sweden)

    Hoda Haghir

    2017-03-01

    Full Text Available Introduction: The evidence has shown that expansion of cardiovascular disease has inflammation base, and general inflammation (systemic plays a pivotal role in the development of atherosclerosis. The purpose of this research was evaluation of changes in intercellular adhesion molecule – 1, vascular adhesion molecule-1 and C – reactive protein in middle-aged men with heart failure after eight weeks of aerobic exercise. Methods: Twenty four middle-aged men with heart failure were selected as volunteers, and were divided into two groups; the aerobic training and the control groups. Aerobic training program was eight weeks, three times per week with the intensity of 40%-70% maximum heart rate. Fasting blood samples were taken from all subjects before and after eight weeks of aerobic exercise. . Data were analyzed by paired sample t-test and independent sample t-test at a significance levels of P<0.05. Results: In the aerobic training group, comparison within groups showed, serum levels of ICAM-1, VCAM-1 and CRP (respectively P=0.001, P=0.001 and P=0.001 were significantly reduced. There was a significant reduction in comparison between groups only for VCAM-1 (P=0.001 and CRP (P=0.002. Conclusion: Aerobic exercise with reducing levels of inflammatory markers ICAM-1 and CRP may play an important role in the prevention and control of cardiovascular diseases in middle-aged men with heart failure.

  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. Inflammatory events at the blood brain barrier: regulation of adhesion molecules, cytokines, and chemokines by reactive nitrogen and oxygen species.

    Science.gov (United States)

    Merrill, J E; Murphy, S P

    1997-12-01

    Recruitment of inflammatory cells into the CNS during pathological processes associated with neurodegeneration, trauma, autoimmune disease, and infection involves the generation of signaling molecules that are both cell-associated and soluble. Alteration in the permeability of the blood brain barrier, adhesion of blood-borne leukocytes to cerebral vessels, activation of chemoattractants and their receptors, and migration of inflammatory cells into the CNS are events that have been proposed to be regulated by cytokines and reactive oxygen and nitrogen species. In this review we propose associative connections between these events and the molecules involved as they may relate to CNS inflammation, placing illustrative emphasis on multiple sclerosis and the animal model for MS, experimental allergic encephalomyelitis.

  19. Nerve/glial antigen (NG) 2 is a crucial regulator of intercellular adhesion molecule (ICAM)-1 expression.

    Science.gov (United States)

    Schmitt, Beate M; Laschke, Matthias W; Rössler, Oliver G; Huang, Wenhui; Scheller, Anja; Menger, Michael D; Ampofo, Emmanuel

    2018-01-01

    The proteoglycan nerve/glial antigen (NG) 2 is expressed on multiple cell types and mediates cell proliferation and migration. However, little is known about its function in gene regulation. In this study, we demonstrate that in pericytes and glioblastoma cells intercellular adhesion molecule (ICAM)-1, an essential protein for leukocyte adhesion and transmigration, underlies a NG2-dependent expression. As shown by flow cytometry, Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR), silencing of NG2 in human placenta-derived pericytes increased the expression of ICAM-1. Pathway analyses revealed that this is mediated by extracellular-regulated-kinases (ERK) 1/2 signaling. Moreover, leukocyte adhesion to NG2 siRNA-treated pericytes was significantly enhanced when compared to scrambled (scr) siRNA-treated control cells. In vivo, we detected increased ICAM-1 protein levels in the retina of mice lacking NG2 expression. To exclude that this novel mechanism is pericyte-specific, we additionally analyzed the expression of ICAM-1 in dependency of NG2 in two glioblastoma cell lines. We found that A1207 and M059K cells exhibit an inverse expression pattern of NG2 and ICAM-1. Finally, downregulation of NG2 in A1207 cells significantly increased ICAM-1 expression. Taken together, these findings indicate that NG2 may represent a promising target for the modulation of ICAM-1-mediated immune responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. In vitro characterization of multivalent adhesion molecule 7-based inhibition of multidrug-resistant bacteria isolated from wounded military personnel

    Science.gov (United States)

    Krachler, Anne Marie; Mende, Katrin; Murray, Clinton; Orth, Kim

    2012-01-01

    Treatment of wounded military personnel at military medical centers is often complicated by colonization and infection of wounds with pathogenic bacteria. These include nosocomially transmitted, often multidrug-resistant pathogens such as Acinetobacter baumannii-calcoaceticus complex, Pseudomonas aeruginosa and extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. We analyzed the efficacy of multivalent adhesion molecule (MAM) 7-based anti-adhesion treatment of host cells against aforementioned pathogens in a tissue culture infection model. Herein, we observed that a correlation between two important hallmarks of virulence, attachment and cytotoxicity, could serve as a useful predictor for the success of MAM7-based inhibition against bacterial infections. Initially, we characterized 20 patient isolates (five from each pathogen mentioned above) in terms of genotypic diversity, antimicrobial susceptibility and important hallmarks of pathogenicity (biofilm formation, attachment to and cytotoxicity toward cultured host cells). All isolates displayed a high degree of genotypic diversity, which was also reflected by large strain-to-strain variability in terms of biofilm formation, attachment and cytotoxicity within each group of pathogen. Using non-pathogenic bacteria expressing MAM7 or latex beads coated with recombinant MAM7 for anti-adhesion treatment, we showed a decrease in cytotoxicity, indicating that MAM7 has potential as a prophylactic agent to attenuate infection by multidrug-resistant bacterial pathogens. PMID:22722243

  1. Inflammation induced by Bothrops asper venom: release of proinflammatory cytokines and eicosanoids, and role of adhesion molecules in leukocyte infiltration.

    Science.gov (United States)

    Zamuner, Stella Regina; Zuliani, Juliana Pavan; Fernandes, Cristina Maria; Gutiérrez, José Maria; de Fátima Pereira Teixeira, Catarina

    2005-12-01

    Bothrops asper venom (BaV) causes systemic and local effects characterized by an acute inflammatory reaction with accumulation of leukocytes and release of endogenous mediators. In this study, the effects of BaV on the release of the cytokines IL-1, IL-6 and TNF-alpha and the eicosanoids LTB4 and TXA2 in the peritoneal cavity of mice were analyzed. We also investigated the participation of beta2 integrin chain, l-selectin, LFA-1, ICAM-1 and PECAM-1 adhesion molecules in the BaV-induced leukocyte accumulation. Levels of proinflammatory cytokines IL-6 and TNF-alpha, as well as eicosanoids LTB4 and TXA2 were significantly increased after BaV injection (250 microg/kg), whereas no increment in IL-1 was observed. Anti-mouse l-selectin, LFA-1, ICAM-1, PECAM-1 and beta2 integrin chain monoclonal antibodies resulted in a reduction of neutrophil accumulation induced by BaV injection compared with isotype-matched control injected animals. These data suggest that BaV is able to induce the activation of leukocytes and endothelium to express adhesion molecules involved in the recruitment of neutrophils into the inflammed site. Furthermore, these results showed that BaV induces the release of cytokines and eicosanoids in the local of the venom injection; these inflammatory mediators may be important for the initiation and amplification of the inflammatory reaction characteristic from Bothrops sp envenomation.

  2. Significance of TNF-α and the Adhesion Molecules: L-Selectin and VCAM-1 in Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Toral P. Kobawala

    2016-01-01

    Full Text Available Circulating levels of TNF-α and the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC have been determined in this study. The serum levels of TNF-α, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-α and L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF-α and L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-α levels significantly positively correlated with the levels of L-Selectin, while TNF-α immunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-α was found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-α and the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer.

  3. Assessment of glycosylation-dependent cell adhesion molecule 1 as a correlate of allergen-stimulated lymph node activation

    International Nuclear Information System (INIS)

    Betts, Catherine J.; Moggs, Jonathan G.; Caddick, Helen T.; Cumberbatch, Marie; Orphanides, George; Dearman, Rebecca J.; Ryan, Cindy A.; Hulette, Ben C.; Frank Gerberick, G.; Kimber, Ian

    2003-01-01

    Early changes in gene expression have been identified by cDNA microarray technology. Analysis of draining auricular lymph node tissue sampled at 48 h following exposure to the potent contact allergen 2,4-dinitrofluorobenzene (DNFB) provided examples of up- and down-regulated genes, including onzin and guanylate binding protein 2, and glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1), respectively. Allergen-induced changes in these three genes were confirmed in dose-response and kinetic analyses using Northern blotting and/or reverse transcription-polymerase chain reaction techniques. The results confirmed that these genes are robust and relatively sensitive markers of early changes provoked in the lymph node by contact allergen. Upon further investigation, it was found that altered expression of the adhesion molecule GlyCAM-1 was not restricted to treatment with DNFB. Topical sensitization of mice to a chemically unrelated contact allergen, oxazolone, was also associated with a decrease in the expression of mRNA for GlyCAM-1. Supplementary experiments revealed that changes in expression of this gene are independent of the stimulation by chemical allergens of proliferative responses by draining lymph node cells. Taken together these data indicate that the expression of GlyCAM-1 is down-regulated rapidly following epicutaneous treatment of mice with chemical allergens, but that this reduction is associated primarily with changes in lymph node cell number, or some other aspect of lymph node activation, rather than proliferation

  4. Effects of dexamethasone on intercellular adhesion molecule 1 expression and inflammatory response in necrotizing acute pancreatitis in rats.

    Science.gov (United States)

    Ramudo, Laura; Yubero, Sara; Manso, Manuel A; Sanchez-Recio, Javier; Weruaga, Eduardo; De Dios, Isabel

    2010-10-01

    Adhesion molecules are involved in the inflammatory response during acute pancreatitis (AP). We investigated the effect of dexamethasone (Dx) on intercellular adhesion molecule 1 (ICAM-1) expression during AP and its consequences on leukocyte recruitment and pancreatic damage. Acute pancreatitis was induced in rats by 3.5% sodium taurocholate for 3 hours and 6 hours. Dexamethasone (1 mg/kg) was administered either 30 minutes before or 1 hour after inducing AP. Messenger RNA ICAM-1 expression in pancreas and lung, membrane-bound ICAM-1 in acinar cells, and ICAM-1 plasma levels were analyzed. Histological examination of the pancreas and neutrophil infiltration in pancreas and lung were also measured. Prophylactic and therapeutic administration of Dx down-regulated ICAM-1 expression in pancreas and lung from early AP. Dexamethasone given before AP reduced the pancreatic damage, but lung inflammation was not prevented. Therapeutic Dx treatment was ineffective in avoiding leukocyte recruitment into the pancreas and lung in rats with AP. High ICAM-1 concentration was found in plasma during AP, which was not reduced by Dx treatments. Dexamethasone down-regulates ICAM-1 expression, but it does not completely prevent leukocyte recruitment during sodium taurocholate-induced AP.

  5. 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

  6. Towards atomic-level mechanics: Adhesive forces between aromatic molecules and carbon nanotubes

    Science.gov (United States)

    Lechner, Christoph; Sax, Alexander F.

    2017-10-01

    The adhesive forces for desorption of the four aromatic compounds benzene, anthracene, pyrene, and tetracene from a (8,0) carbon nanotube (CNT) are investigated and compared to the desorption from graphene. The desorption energies are found to be proportional to the size of the contact zone in the adsorbent/adsorbate complex while maximum adhesive forces are proportional to the part of the contact zone where attractive interactions are reduced when external forces pull on the adsorbate. To assess the influence of the curvature, type of CNT, and the adsorbate's orientation, the desorption processes from six zigzag CNT and four armchair CNT are studied for pyrene and tetracene. For some properties, the results are independent of the curvature of the adsorbent, whereas for others we find marked differences. Aspects of elasticity are considered as well as the influence of the Pauli exclusion principle on the equilibrium geometries in adsorbent/adsorbate complexes.

  7. Inhibition of tumor necrosis factor-α-induced expression of adhesion molecules in human endothelial cells by the saponins derived from roots of Platycodon grandiflorum

    International Nuclear Information System (INIS)

    Kim, Ji Young; Kim, Dong Hee; Kim, Hyung Gyun; Song, Gyu-Yong; Chung, Young Chul; Roh, Seong Hwan; Jeong, Hye Gwang

    2006-01-01

    Adhesion molecules play an important role in the development of atherogenesis and are produced by endothelial cells after being stimulated with various inflammatory cytokines. This study examined the effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. CKS significantly inhibited the TNFα-induced increase in monocyte adhesion to endothelial cells as well as decreased the protein and mRNA expression levels of vascular adhesion molecule-1 and intercellular cell adhesion molecule-1 on endothelial cells. Furthermore, CKS significantly inhibited the TNFα-induced production of intracellular reactive oxygen species (ROS) and activation of NF-κB by preventing IκB degradation and inhibiting IκB kinase activity. Overall, CKS has anti-atherosclerotic and anti-inflammatory activity, which is least in part the result of it reducing the cytokine-induced endothelial adhesion to monocytes by inhibiting intracellular ROS production, NF-κB activation, and cell adhesion molecule expression in endothelial cells

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

    Science.gov (United States)

    Mikkelsen, Lone; Jensen, Keld A; Koponen, Ismo K; Saber, Anne T; Wallin, Håkan; Loft, Steffen; Vogel, Ulla; Møller, Peter

    2013-03-01

    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 cells were exposed to primary nanoparticles (fine, photocatalytic or nanosized TiO(2), aluminium silicate, carbon black, nano-silicasol or axilate) and dust from sanding reference- or nanoparticle-containing paints. Most of the samples increased cell surface expressions of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), but paint sanding dust samples generally generated less response than primary particles of TiO(2) and carbon black. We found no relationship between the expression of adhesion molecules, cytotoxicity and production of reactive oxygen species. In conclusion, sanding dust from nanoparticle-containing paint did not generate more oxidative stress or expression of cell adhesion molecules than sanding dust from paint without nanoparticles, whereas the primary particles had the largest effect on mass basis.

  9. 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.

  10. Streptococcus pyogenes Phospholipase A2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice.

    Science.gov (United States)

    Oda, Masataka; Domon, Hisanori; Kurosawa, Mie; Isono, Toshihito; Maekawa, Tomoki; Yamaguchi, Masaya; Kawabata, Shigetada; Terao, Yutaka

    2017-01-01

    The Streptococcus pyogenes phospholipase A 2 (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 Δ slaA 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.

  11. Intercellular adhesion molecule-1/LFA-1 ligation favors human Th1 development

    NARCIS (Netherlands)

    Smits, Hermelijn H.; de Jong, Esther C.; Schuitemaker, Joost H. N.; Geijtenbeek, Theo B. H.; van Kooyk, Yvette; Kapsenberg, Martien L.; Wierenga, Eddy A.

    2002-01-01

    Th cell polarization toward Th1 or Th2 cells is strongly driven by exogenous cytokines, in particular IL-12 or IL-4, if present during activation by Ag-presenting dendritic cells (DC). However, additional Th cell polarizing mechanisms are induced by the ligation of cell surface molecules on DC and

  12. Inside-out signaling promotes dynamic changes in the carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) oligomeric state to control its cell adhesion properties.

    Science.gov (United States)

    Patel, Prerna C; Lee, Hannah S W; Ming, Aaron Y K; Rath, Arianna; Deber, Charles M; Yip, Christopher M; Rocheleau, Jonathan V; Gray-Owen, Scott D

    2013-10-11

    Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) can engage in both cis-homophilic (parallel) oligomerization and trans-homophilic (anti-parallel) binding. In this study, we establish that the CEACAM1 transmembrane domain has a propensity to form cis-dimers via the transmembrane-embedded (432)GXXXG(436) motif and that this basal state is overcome when activated calmodulin binds to the CEACAM1 cytoplasmic domain. Although mutation of the (432)GXXXG(436) motif reduced CEACAM1 oligomerization, it did not affect surface localization of the receptor or influence CEACAM1-dependent cellular invasion by the pathogenic Neisseria. The mutation did, however, have a striking effect on CEACAM1-dependent cellular aggregation, increasing both the kinetics of cell-cell association and the size of cellular aggregates formed. CEACAM1 association with tyrosine kinase c-Src and tyrosine phosphatases SHP-1 and SHP-2 was not affected by the (432)GXXXG(436) mutation, consistent with their association with the monomeric form of wild type CEACAM1. Collectively, our results establish that a dynamic oligomer-to-monomer shift in surface-expressed CEACAM1 facilitates trans-homophilic binding and downstream effector signaling.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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

    Following cardiac surgery with cardiopulmonary bypass (CPB), activated granulocytes may be involved with ischaemia/ reperfusion injury. The purpose of this study was to investigate whether steroids could reduce the oxidative burst activity of granulocytes, the expression of adhesion molecules...... on 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...

  15. How relevant are vascular endothelial growth factor and intercellular adhesion molecule in the systemic capillary leak syndrome of psoriasis?*

    Science.gov (United States)

    Bressan, Aline Lopes; Pereira, Daniele; Medeiros, Paula Mota; Carneiro, Sueli; Azulay-Abulafia, Luna

    2017-01-01

    Psoriasis is a chronic disease, characterized by erythematous scaly lesions, presented in eight different forms: plaques, guttate, pustular, erythrodermic, inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development depends on genetic factors, external stimulus and immune response alteration.1 Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved. In the worst cases, systemic complications linked to endothelial alterations may occur. A literature review was conducted for a better understanding of what roles VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion molecule) have, among other cytokines, in systemic capillary leak syndrome, involved in erythrodermic and pustular psoriasis, the most unstable forms of the disease. PMID:29364440

  16. Synthesis of pro-inflammatory cytokines and adhesion molecules expression by the irradiated human monocyte/macrophage

    International Nuclear Information System (INIS)

    Pons, I.

    1997-09-01

    As lesions induced by ionizing radiations are essentially noticed in organs the functional and structural organisation of which depend on the highly proliferative stem cell pool, the author reports an in-vivo investigation of the effect of a gamma irradiation on the expression and secretion of pro-inflammatory cytokines par human monocytes/macrophages. In order to study the role of the cell environment in the radiation-induced inflammation, the author studied whether a co-stimulation of monocytes/macrophages by gamma irradiation, or the exposure of co-cultures of monocytes/macrophages and lymphocytes, could modulate the regulation of inflammatory cytokines. The author also studied the modulation of the expression of adhesion molecules mainly expressed by the monocyte/macrophage, and the membrane density of the CD14 receptor after irradiation of monocytes/macrophages during 24 hours, and of totally differentiated macrophages after seven days of culture

  17. Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Cai, Guoping; Lai, Binbin; Hong, Huaxing; Lin, Peng; Chen, Weifu; Zhu, Zhong; Chen, Haixiao

    2017-07-01

    Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin‑1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule‑1 (ICAM‑1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue‑engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post‑cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM‑1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube‑like structure‑forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time‑dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue‑engineered microvascular construction.

  18. Mesenchymal Stem Cells in Perichondrium Express Activated Leukocyte Cell Adhesion Molecule and Participate in Bone Marrow Formation

    Science.gov (United States)

    Arai, Fumio; Ohneda, Osamu; Miyamoto, Takeshi; Zhang, Xiu Qin; Suda, Toshio

    2002-01-01

    Perichondrium in fetal limb is composed of undifferentiated mesenchymal cells. However, the multipotency of cells in this region and the role of perichondrium in bone marrow formation are not well understood. In this report, we purified and characterized perichondrial cells using a monoclonal antibody against activated leukocyte cell adhesion molecule (ALCAM) and investigated the role of perichondrial cells in hematopoietic bone marrow formation. ALCAM is expressed on hematopoietic cells, endothelial cells, bone marrow stromal cells, and mesenchymal stem cells and mediates homophilic (ALCAM–ALCAM)/heterophilic (ALCAM-CD6) cell adhesion. Here we show by immunohistochemical staining that ALCAM is expressed in perichondrium. ALCAM+ perichondrial cells isolated by FACS® exhibit the characteristics of mesenchymal stem cells. ALCAM+ cells can differentiate into osteoblasts, adipocytes, chondrocytes, and stromal cells, which can support osteoclastogenesis, hematopoiesis, and angiogenesis. Furthermore, the addition of ALCAM-Fc or CD6-Fc to the metatarsal culture, the invasion of the blood vessels to a cartilage was inhibited. Our findings indicate that ALCAM+ perichondrial cells participate in vascular invasion by recruiting osteoclasts and vessels. These findings suggest that perichondrium might serve as a stem cell reservoir and play an important role in the early development of a bone and bone marrow. PMID:12070283

  19. Interaction of DDSDEEN peptide with N-CAM protein. Possible mechanism enhancing neuronal differentiation.

    Science.gov (United States)

    Marsili, Valeria; Lupidi, Giulio; Berellini, Giuliano; Calzuola, Isabella; Perni, Stefano; Cruciani, Gabriele; Gianfranceschi, Gian Luigi

    2008-12-01

    DDSDEEN chromatin peptide, after dansylation, was studied for its ability to bind N-CAM protein. The binding causes a quenching of the Dns-peptide fluorescence emission. Dose- and time-dependent binding of Dns-peptide with N-CAM has been shown. Fluorescence quenching is completely lost if the Dns-peptide is subjected to carboxypeptidase digestion. Moreover the undansylated peptide pEDDSDEEN competes with the DnsDDSDEEN peptide for the binding with the N-CAM protein. The Dns-peptide-N-CAM bond has been related to the peptide biological activity probably involved in the promotion of neuronal differentiation. An attempt to recognize a possible N-CAM binding site for Dns-peptide was performed by alignment of N-CAM from various sources with some sequences that have been previously reported as binding sites for the pEDDSDEEN and DDSDEEN peptides. Interestingly, the alignment of N-CAM from various sources with the peptides WHPREGWAL and WFPRWAGQA recognizes on rat and human N-CAM a unique sequence that could be the specific binding site for chromatin peptide: WHSKWYDAK. This sequence is present in fibronectin type-III domain of N-CAM. In addition molecular modeling studies indicate the N-CAM sequence WHSKWYDAK as, probably, the main active site for DnsDDSDEEN (or pEDDSDEEN) peptide ligand. Accordingly the binding experiments show a high affinity between WHSKWYDAK and DnsDDSDEEN peptides.

  20. L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.

    Directory of Open Access Journals (Sweden)

    Cássia G T Silveira

    Full Text Available BACKGROUND/AIMS: The neural cell adhesion molecule L1CAM is a transmembrane glycoprotein abnormally expressed in tumors and previously associated with cell proliferation, adhesion and invasion, as well as neurite outgrowth in endometriosis. Being an attractive target molecule for antibody-based therapy, the present study assessed the ability of the monoclonal anti-L1 antibody (anti-L1 mAb to impair the development of endometriotic lesions in vivo and endometriosis-associated nerve fiber growth. METHODS AND RESULTS: Endometriosis was experimentally induced in sexually mature B6C3F1 (n=34 and CD-1 nude (n=21 mice by autologous and heterologous transplantation, respectively, of endometrial fragments into the peritoneal cavity. Transplantation was confirmed four weeks post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively. Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype control antibody twice weekly, over a period of four weeks. Upon treatment completion, mice were sacrificed and endometrial implants were excised, measured and fixed. Endometriosis was histologically confirmed and L1CAM was detected by immunohistochemistry. Endometriotic lesion size was significantly reduced in anti-L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control antibody (P<0.05. Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039. CONCLUSIONS: Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent

  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-6

  2. 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

  3. 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

  4. Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation.

    Directory of Open Access Journals (Sweden)

    Junko Mima

    Full Text Available Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1(-/- mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1(-/- mice. TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(-/-mice. However, CEACAM1 expression was retained in the remaining MEE of TGFβ-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.

  5. 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.

  6. NADPH oxidase and lipid raft-associated redox signaling are required for PCB153-induced upregulation of cell adhesion molecules in human brain endothelial cells

    International Nuclear Information System (INIS)

    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.

  7. Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules.

    Science.gov (United States)

    Montico, Fábio; Hetzl, Amanda Cia; Cândido, Eduardo Marcelo; Fávaro, Wagner José; Cagnon, Valéria Helena Alves

    2011-08-01

    Hormonal replacement has been utilized to minimize the harmful effects of hormonal imbalance in elderly men. The development and progression of prostatic diseases and their relation to hormone therapy is still unclear. Thus, the aim herewith was to characterize the structure and dystroglycan molecule (DGs) reactivities in the ventral prostatic lobe from elderly rats submitted to steroid hormone replacement. Male rats (Sprague-Dawley) were divided into one Young group and six senile groups. The Young group (YNG) (4 months old) received peanut oil (5mL/kg, s.c.). The senile rats (10 months old) were submitted to the following treatments: Senile group (SEN) (5mL/kg peanut oil, s.c.); Testosterone group (TEST) (5mg/kg testosterone cipionate, s.c.); Estrogen group (EST) (25μg/kg 17β-estradiol, s.c.); Castrated group (CAS) (surgical castration); Castrated-Testosterone (CT) (surgical castration and treatment similar to TEST group); and Castrated-Estrogen (CE) (surgical castration and treatment similar to EST group). After 30 days treatment, blood samples were collected for hormonal analysis and ventral prostate samples were processed for light and transmission electron microscopies, morphometrical analysis, immunohistochemistry and Western Blotting. The results showed decreased serum testosterone levels in the senescence and increased testosterone and estrogen plasmatic levels after hormone administration in the TEST and EST groups, respectively, highlighting the therapy efficiency. Hypertrophied stroma and inflammatory cells were verified in the SEN group. After hormone replacement in the senescence or following castration, atrophic epithelium, epithelial cells with clear cytoplasmic halo around the nucleus, microacini and maintenance of hypertrophied stroma were seen. Decreased DG levels were verified in the senescence. After hormonal therapy, increased protein levels of these molecules were observed, especially in those groups which received estradiol. Thus, the

  8. 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.

    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

  9. 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

  10. 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 II...

  11. 1α,25-Dihydroxyvitamin D(3) inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cells.

    Science.gov (United States)

    Kudo, Keiko; Hasegawa, Shunji; Suzuki, Yasuo; Hirano, Reiji; Wakiguchi, Hiroyuki; Kittaka, Setsuaki; Ichiyama, Takashi

    2012-11-01

    Kawasaki disease is an acute febrile vasculitis of childhood that is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. The production of proinflammatory cytokines and expression of adhesion molecules in human coronary arterial endothelial cells (HCAECs) is regulated by nuclear transcription factor-κB (NF-κB) activation. We have previously reported that the active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)), inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activation. In this study, we examined the anti-inflammatory effects of 1α,25-(OH)(2)D(3) on TNF-α-induced adhesion molecule expression (vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)) and cytokine production (interleukin-6 (IL-6) and IL-8) in HCAECs. Pretreatment with 1α,25-(OH)(2)D(3) significantly inhibited TNF-α-induced VCAM-1 expression and IL-8 production in HCAECs. Our results suggest that adjunctive 1α,25-(OH)(2)D(3) therapy may modulate the inflammatory response during Kawasaki disease vasculitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers

    NARCIS (Netherlands)

    Tits, van L.J.; Waart, de F.; Hak-Lemmers, H.L.M.; Heijst, P.; Graaf, de J.; Demacker, P.N.; Stalenhoef, A.F.

    2001-01-01

    Antioxidants have been postulated to exert beneficial effects in atherosclerosis. Atherosclerosis is associated with raised plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and autoantibodies against oxidized low-density lipoprotein (oxLDL). It is not known whether antioxidants

  13. Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers.

    NARCIS (Netherlands)

    Tits, L.J.H. van; Waart, F. de; Hak-Lemmers, H.L.M.; Heijst, P. van; Graaf, J. de; Demacker, P.N.M.; Stalenhoef, A.F.H.

    2001-01-01

    Antioxidants have been postulated to exert beneficial effects in atherosclerosis. Atherosclerosis is associated with raised plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and autoantibodies against oxidized low-density lipoprotein (oxLDL). It is not known whether antioxidants

  14. 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, Else Kirstine

    1998-01-01

    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...

  15. 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

    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-treated...

  16. CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2...

  17. Nucleotide-binding oligomerization domain 1 regulates Porphyromonas gingivalis-induced vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression in endothelial cells through NF-κB pathway.

    Science.gov (United States)

    Wan, M; Liu, J; Ouyang, X

    2015-04-01

    Porphyromonas gingivalis has been shown to actively invade endothelial cells and induce vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) overexpression. Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular pattern recognition reporter, and its involvement in this process was unknown. This study focused on endothelial cells infected with P. gingivalis, the detection of NOD1 expression and the role that NOD1 plays in the upregulation of VCAM-1 and ICAM-1. The human umbilical vein endothelial cell line (ECV-304) was intruded by P. gingivalis W83, and cells without any treatment were the control group. Expression levels of NOD1, VCAM-1, ICAM-1, phosphorylated P65 between cells with and without treatment on both mRNA and protein levels were compared. Then we examined whether mesodiaminopimelic acid (NOD1 agonist) could increase VCAM-1 and ICAM-1 expression, meanwhile, NOD1 gene silence by RNA interference could reduce VCAM-1, ICAM-1 and phosphorylated P65 release. At last, we examined whether inhibition of NF-κB by Bay117082 could reduce VCAM-1 and ICAM- 1 expression. The mRNA levels were measured by real-time polymerase chain reaction, and protein levels by western blot or electrophoretic mobility shift assays (for phosphorylated P65). P. gingivalis invasion showed significant upregulation of NOD1, VCAM-1 and ICAM-1. NOD1 activation by meso-diaminopimelic acid increased VCAM-1 and ICAM-1 expression, and NOD1 gene silence reduced VCAM-1 and ICAM-1 release markedly. The NF-κB signaling pathway was activated by P. gingivalis, while NOD1 gene silence decreased the activation of NF-κB. Moreover, inhibition of NF-κB reduced VCAM-1 and ICAM-1 expression induced by P. gingivalis in endothelial cells. The results revealed that P. gingivalis induced NOD1 overexpression in endothelial cells and that NOD1 played an important role in the process of VCAM-1 and ICAM-1 expression in endothelial cells infected with P

  18. Implication of Soluble Forms of Cell Adhesion Molecules in Infectious Disease and Tumor: Insights from Transgenic Animal Models

    Directory of Open Access Journals (Sweden)

    Etsuro Ono

    2018-01-01

    Full Text Available Cell adhesion molecules (CAMs are surface ligands, usually glycoproteins, which mediate cell-to-cell adhesion. They play a critical role in maintaining tissue integrity and mediating migration of cells, and some of them also act as viral receptors. It has been known that soluble forms of the viral receptors bind to the surface glycoproteins of the viruses and neutralize them, resulting in inhibition of the viral entry into cells. Nectin-1 is one of important CAMs belonging to immunoglobulin superfamily and herpesvirus entry mediator (HVEM is a member of the tumor necrosis factor (TNF receptor family. Both CAMs also act as alphaherpesvirus receptor. Transgenic mice expressing the soluble form of nectin-1 or HVEM showed almost complete resistance against the alphaherpesviruses. As another CAM, sialic acid-binding immunoglobulin-like lectins (Siglecs that recognize sialic acids are also known as an immunoglobulin superfamily member. Siglecs play an important role in the regulation of immune cell functions in infectious diseases, inflammation, neurodegeneration, autoimmune diseases and cancer. Siglec-9 is one of Siglecs and capsular polysaccharide (CPS of group B Streptococcus (GBS binds to Siglec-9 on neutrophils, leading to suppress host immune response and provide a survival advantage to the pathogen. In addition, Siglec-9 also binds to tumor-produced mucins such as MUC1 to lead negative immunomodulation. Transgenic mice expressing the soluble form of Siglec-9 showed significant resistance against GBS infection and remarkable suppression of MUC1 expressing tumor proliferation. This review describes recent developments in the understanding of the potency of soluble forms of CAMs in the transgenic mice and discusses potential therapeutic interventions that may alter the outcomes of certain diseases.

  19. 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.

  20. 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.

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

    DEFF Research Database (Denmark)

    Kolkova, K; Novitskaya, V; Pedersen, N

    2000-01-01

    , inhibitors of the nonreceptor tyrosine kinase p59(fyn), PLC, PKC and MEK and an activator of PKC, phorbol-12-myristate-13-acetate (PMA). MEK2 transfection rescued cells treated with all inhibitors. The same was found for PMA treatment, except when cells concomitantly were treated with the MEK inhibitor....... Arachidonic acid rescued cells treated with antibodies to the FGF receptor or the PLC inhibitor, but not cells in which the activity of PKC, p59(fyn), FAK, Ras, or MEK was inhibited. Interaction of NCAM with a synthetic NCAM peptide ligand, known to induce neurite outgrowth, was shown to stimulate...

  2. Characterization of epithelial domains in the nasal passages of chick embryos: spatial and temporal mapping of a range of extracellular matrix and cell surface molecules during development of the nasal placode.

    Science.gov (United States)

    Croucher, S J; Tickle, C

    1989-07-01

    The formation of the nasal passages involves complex morphogenesis and their lining develops a spatially ordered pattern of differentiation, with distinct domains of olfactory and respiratory epithelium. Using antibodies to the neural cell adhesion molecule (N-CAM), keratan sulphate and heparan sulphate proteoglycan (HSPG) and a panel of lectins (agglutinins of Canavalia ensiformis (ConA), Dolichos biflorus (DBA), peanut (PNA), Ricinis communis (RCA1), soybean (SBA), Ulex europaeus (UEA1), and wheatgerm (WGA], we have documented cell surface characteristics of each epithelial domain. Binding of antibodies to N-CAM and to keratan sulphate, and the lectins ConA, PNA, RCA1, SBA and WGA marks the olfactory epithelial domain only. The restriction of N-CAM to the sensory region of the epithelium has also been reported in the developing ear. This striking similarity is consistent with the idea that N-CAM may be involved in the division of functionally and histologically distinct cell groups within an epithelium. We traced the olfactory-specific cell markers during development to gain insights into the origin of the epithelial lining of the nasal passages. All reagents bind at early stages to the thickened nasal placode and surrounding head ectoderm and then become progressively restricted to the olfactory domain. The expression of these characteristics appears to be modulated during development rather than being cell autonomous. The distribution of keratan sulphate was compared with collagen type II in relation to the specification of the chondrocranium. Keratan sulphate and collagen type II are only colocalized at the epithelial-mesenchymal interface during early nasal development. At later stages, only collagen type II is expressed at the interface throughout the nasal passages, whereas keratan sulphate is absent beneath the respiratory epithelium.

  3. Trimebutine, a small molecule mimetic agonist of adhesion molecule L1, contributes to functional recovery after spinal cord injury in mice

    Directory of Open Access Journals (Sweden)

    Junping Xu

    2017-09-01

    Full Text Available Curing spinal cord injury (SCI in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1 has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity but delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans. We have, therefore, identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration and neurite outgrowth in an L1-dependent manner. Here, we assessed the functions of two L1 mimetics, trimebutine and honokiol, in regeneration following SCI in young adult mice. Using the Basso Mouse Scale (BMS score, we found that ground locomotion in trimebutine-treated mice recovered better than honokiol-treated or vehicle-receiving mice. Enhanced hindlimb locomotor functions in the trimebutine group were observed at 6 weeks after SCI. Immunohistology of the spinal cords rostral and caudal to the lesion site showed reduced areas and intensities of glial fibrillary acidic protein immunoreactivity in both trimebutine and honokiol groups, whereas increased regrowth of axons was observed only in the trimebutine-treated group. Both L1- and L1 mimetic-mediated intracellular signaling cascades in the spinal cord lesion sites were activated by trimebutine and honokiol, with trimebutine being more effective than honokiol. These observations suggest that trimebutine and, to a lesser extent under the present experimental conditions, honokiol have a potential for therapy in regeneration of mammalian spinal cord injuries.

  4. The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Tun-Pin Hsueh

    2016-02-01

    Full Text Available 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.

  5. 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.

  6. A Phenanthrene Derivative, 5,7-Dimethoxy-1,4-Phenanthrenequinone, Inhibits Cell Adhesion Molecule Expression and Migration in Vascular Endothelial and Smooth Muscle Cells.

    Science.gov (United States)

    Lo, Huey-Ming; Hwang, Tsong-Long; Wu, Wen-Bin

    2017-01-01

    The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs. The DMPQ attenuated monocyte-EC interaction but it did not affect monocyte adhesion to matrix. In parallel, DMPQ reduced tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule and vascular CAM expression in ECs. DMPQ compromised TNF-α-induced IκB activation, nuclear factor-kappa B (NF-κB) translocation, and NF-κB-DNA complex formation. Moreover, it affected TNF-α- and hydrogen peroxide (H2O2)-induced reactive oxygen species production and IκB activation. These suggest that DMPQ affects CAM expression by affecting NF-κB signaling. Meanwhile, DMPQ could also inhibit platelet-derived growth factor (PDGF)-induced VSMC migration toward collagen by affecting cellular PDGF signaling, including PDGFRβ, PLCγ, ERK1/2, and Akt phosphorylation. The VSMC adhesion to collagen and collagen-induced focal adhesion kinase activation during cell adhesion were impaired by DMPQ treatment. This study reveals a phenanthrene derivative-DMPQ-with anti-inflammatory and anti-migratory bioactivity toward vascular ECs and SMCs, suggesting its protective effect on vascular injuries. © 2017 S. Karger AG, Basel.

  7. Multivalent adhesion molecule 7 clusters act as signaling platform for host cellular GTPase activation and facilitate epithelial barrier dysfunction.

    Directory of Open Access Journals (Sweden)

    Jenson Lim

    2014-09-01

    Full Text Available Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen.

  8. 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.

  9. MIP-1α enhances Jurkat cell transendothelial migration by up-regulating endothelial adhesion molecules VCAM-1 and ICAM-1.

    Science.gov (United States)

    Ma, Yi-Ran; Ma, Ying-Huan

    2014-11-01

    The aim of this study is to evaluate the expression of macrophage inflammatory protein-1α (MIP-1α) in Jurkat cells and its effect on transendothelial migration. In the present study, human acute lymphoblastic leukemia Jurkat cells (Jurkat cells) were used as a model of T cells in human T-cell acute lymphoblastic leukemia (T-ALL), which demonstrated significantly higher MIP-1α expression compared with that in normal T-cell controls. The ability of Jurkat cells to cross a human brain microvascular endothelial cell (HBMEC) monolayer was almost completely abrogated by MIP-1α siRNA. In addition, the overexpression of MIP-1α resulted in the up-regulated expression of endothelial adhesion molecules, which enhanced the migration of Jurkat cells through a monolayer of HBMEC. MIP-1α levels in Jurkat cells appeared to be an important factor for its transendothelial migration, which may provide the theoretical basis to understand the mechanisms of brain metastases of T-ALL at cellular and molecular levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Detection of circulating methylated opioid binding protein/cell adhesion molecule-like gene as a biomarker for ovarian carcinoma.

    Science.gov (United States)

    Zhou, Feng; Ma, Min; Tao, Guohua; Chen, Xiang; Xie, Wei; Wang, Ying; Cao, Xingjian

    2014-01-01

    Hypermethylation of the opioid binding protein/cell adhesion molecule-like (OPCML) gene is frequently observed in ovarian carcinoma. We evaluated the detection of circulating hypermethylated OPCML for detecting ovarian carcinoma and assessing its prognosis. We studied 85 tissue samples including 45 ovarian cancer tissues and 40 normal ovarian tissues and blood samples from 45 ovarian cancer patients and 20 healthy individuals. Bisulfite sequencing and methylation-sensitive restriction enzyme-PCR (MSRE-PCR) were used to detect the frequency of OPCML hypermethylation. We detected that the frequency of OPCML hypermethylation for tissue and serum samples in ovarian carcinoma were 86.7% (39/45) and 80.0% (36/45), respectively, but none was detected in ovarian tissue and serum of healthy individuals. The frequency of OPCML hypermethylation in endometrioid carcinoma, serous cystadenocarcinoma, mucinous cystadenocarcinoma, clear cell carcinoma, and undifferentiated carcinoma were 80.0%, 85.5%, 50.0%, 80.0%, and 100%, respectively (p > 0.05). The frequencies of OPCML hypermethylation in patients were also different in terms of tumor differentiation degree. We detected hypermethylated OPCML in the sera of 50% of well differentiated, 62.5% of moderately differentiated, 93.1% of poorly differentiated tumors (p ovarian carcinoma diagnosis.

  11. The effect of lifestyle intervention in obesity on the soluble form of activated leukocyte cell adhesion molecule.

    Science.gov (United States)

    Sulaj, Alba; Zemva, Johanna; Zech, Ulrike; Woehning, Annika; Brune, Maik; Rudofsky, Gottfried; Nawroth, Peter P; Fleming, Thomas; von Bauer, Rüdiger

    2016-10-13

    The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters. Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined. Oral glucose tolerance test (OGTT) was performed when indicated. At baseline, the serum concentration of sALCAM was increased and correlated positively with HOMA-IR and negatively with age. At the end of the program, sALCAM concentrations decreased significantly. Multivariate analysis showed that sALCAM significantly correlated with age, glucose concentration after 2 h OGTT and the HOMA-IR. A higher decrease of HOMA-IR during the study was observed in subjects with higher concentration of sALCAM at baseline. sALCAM might be a novel biomarker in obesity that correlates and predicts insulin sensitivity improvement and that can be affected by lifestyle intervention.

  12. Roles of specific membrane lipid domains in EGF receptor activation and cell adhesion molecule stabilization in a developing olfactory system.

    Science.gov (United States)

    Gibson, Nicholas J; Tolbert, Leslie P; Oland, Lynne A

    2009-09-29

    Reciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors (EGFRs) and the cell adhesion molecules (IgCAMs) neuroglian and fasciclin II are known to be important players in these processes. We report in situ and cell-culture studies that suggest a role for glycosphingolipid-rich membrane subdomains in neuron-glia interactions. Disruption of these subdomains by the use of methyl-beta-cyclodextrin results in loss of EGFR activation, depletion of fasciclin II in ORN axons, and loss of neuroglian stabilization in the membrane. At the cellular level, disruption leads to aberrant ORN axon trajectories, small antennal lobes, abnormal arrays of olfactory glomerul, and loss of normal glial cell migration. We propose that glycosphingolipid-rich membrane subdomains (possible membrane rafts or platforms) are essential for IgCAM-mediated EGFR activation and for anchoring of neuroglian to the cytoskeleton, both required for normal extension and sorting of ORN axons.

  13. Targeted methylation of the epithelial cell adhesion molecule (EpCAM promoter to silence its expression in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Suneetha Nunna

    Full Text Available The Epithelial Cell Adhesion Molecule (EpCAM is overexpressed in many cancers including ovarian cancer and EpCAM overexpression correlates with decreased survival of patients. It was the aim of this study to achieve a targeted methylation of the EpCAM promoter and silence EpCAM gene expression using an engineered zinc finger protein that specifically binds the EpCAM promoter fused to the catalytic domain of the Dnmt3a DNA methyltransferase. We show that transient transfection of this construct increased the methylation of the EpCAM promoter in SKOV3 cells from 4-8% in untreated cells to 30%. Up to 48% methylation was observed in stable cell lines which express the chimeric methyltransferase. Control experiments confirmed that the methylation was dependent on the fusion of the Zinc finger and the methyltransferase domains and specific for the target region. The stable cell lines with methylated EpCAM promoter showed a 60-80% reduction of EpCAM expression as determined at mRNA and protein level and exhibited a significantly reduced cell proliferation. Our data indicate that targeted methylation of the EpCAM promoter could be an approach in the therapy of EpCAM overexpressing cancers.

  14. Carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 as biomarkers in pancreatic cancer.

    Science.gov (United States)

    Gebauer, Florian; Wicklein, Daniel; Horst, Jennifer; Sundermann, Philipp; Maar, Hanna; Streichert, Thomas; Tachezy, Michael; Izbicki, Jakob R; Bockhorn, Maximilian; Schumacher, Udo

    2014-01-01

    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). 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. 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. 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.

  15. Carcinoembryonic antigen-related cell adhesion molecules (CEACAM 1, 5 and 6 as biomarkers in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Interleukin-6, intracellular adhesion molecule-1, and glycodelin A levels in serum and peritoneal fluid as biomarkers for endometriosis.

    Science.gov (United States)

    Mosbah, Alaa; Nabiel, Yasmin; Khashaba, Eman

    2016-09-01

    To compare levels of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), and glycodelin A in serum and peritoneal fluid of patients with and without endometriosis, and to correlate levels with disease stage. An observational study was undertaken at Mansoura University Hospital, Egypt, between March 2014 and June 2015. Patients aged 21-48 years laparoscopically diagnosed with endometriosis and those without endometriosis who underwent laparoscopy for tubal ligation were included. Levels of IL-6, ICAM-1, and glycodelin A were measured in samples of serum and peritoneal fluid. Receiver operating characteristic curves were used to evaluate diagnostic accuracy. Forty-eight women with endometriosis and 20 without the disorder were included. IL-6 and glycodelin A levels in serum and peritoneal fluid were higher in the endometriosis group than in the control group (Pperitoneal fluid markers were 85.4% and 89.0%, 60.4% and 50.0%, and 89.6% and 90.0%, respectively. IL-6 and glycodelin A levels in serum and peritoneal fluid increased with disease stage (Pendometriosis and are positively correlated with the disease stage. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

    International Nuclear Information System (INIS)

    Zander, Hilke; Kaifi, Jussuf; Rawnaq, Tamina; Wedemeyer, Max von; Tachezy, Michael; Kunkel, Miriam; Wolters, Gerrit; Bockhorn, Maximilian; Schachner, Melitta; Izbicki, Jakob R

    2011-01-01

    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. 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. Median levels of soluble L1 were significantly higher (p < 0.001; Mann-Whitney U test) in sera of GIST patients compared to healthy individuals. Median soluble L1 levels were particularly elevated in patients with recurrence and relapse (p < 0.05; Mann Whitney U test). 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

  19. 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.

  20. Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

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    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.

  1. Soluble melanoma cell adhesion molecule (sMCAM/sCD146) promotes angiogenic effects on endothelial progenitor cells through angiomotin.

    Science.gov (United States)

    Stalin, Jimmy; Harhouri, Karim; Hubert, Lucas; Subrini, Caroline; Lafitte, Daniel; Lissitzky, Jean-Claude; Elganfoud, Nadia; Robert, Stéphane; Foucault-Bertaud, Alexandrine; Kaspi, Elise; Sabatier, Florence; Aurrand-Lions, Michel; Bardin, Nathalie; Holmgren, Lars; Dignat-George, Françoise; Blot-Chabaud, Marcel

    2013-03-29

    The melanoma cell adhesion molecule (CD146) contains a circulating proteolytic variant (sCD146), which is involved in inflammation and angiogenesis. Its circulating level is modulated in different pathologies, but its intracellular transduction pathways are still largely unknown. Using peptide pulldown and mass spectrometry, we identified angiomotin as a sCD146-associated protein in endothelial progenitor cells (EPC). Interaction between angiomotin and sCD146 was confirmed by enzyme-linked immunosorbent assay (ELISA), homogeneous time-resolved fluorescence, and binding of sCD146 on both immobilized recombinant angiomotin and angiomotin-transfected cells. Silencing angiomotin in EPC inhibited sCD146 angiogenic effects, i.e. EPC migration, proliferation, and capacity to form capillary-like structures in Matrigel. In addition, sCD146 effects were inhibited by the angiomotin inhibitor angiostatin and competition with recombinant angiomotin. Finally, binding of sCD146 on angiomotin triggered the activation of several transduction pathways that were identified by antibody array. These results delineate a novel signaling pathway where sCD146 binds to angiomotin to stimulate a proangiogenic response. This result is important to find novel target cells of sCD146 and for the development of therapeutic strategies based on EPC in the treatment of ischemic diseases.

  2. Soluble Melanoma Cell Adhesion Molecule (sMCAM/sCD146) Promotes Angiogenic Effects on Endothelial Progenitor Cells through Angiomotin*

    Science.gov (United States)

    Stalin, Jimmy; Harhouri, Karim; Hubert, Lucas; Subrini, Caroline; Lafitte, Daniel; Lissitzky, Jean-Claude; Elganfoud, Nadia; Robert, Stéphane; Foucault-Bertaud, Alexandrine; Kaspi, Elise; Sabatier, Florence; Aurrand-Lions, Michel; Bardin, Nathalie; Holmgren, Lars; Dignat-George, Françoise; Blot-Chabaud, Marcel

    2013-01-01

    The melanoma cell adhesion molecule (CD146) contains a circulating proteolytic variant (sCD146), which is involved in inflammation and angiogenesis. Its circulating level is modulated in different pathologies, but its intracellular transduction pathways are still largely unknown. Using peptide pulldown and mass spectrometry, we identified angiomotin as a sCD146-associated protein in endothelial progenitor cells (EPC). Interaction between angiomotin and sCD146 was confirmed by enzyme-linked immunosorbent assay (ELISA), homogeneous time-resolved fluorescence, and binding of sCD146 on both immobilized recombinant angiomotin and angiomotin-transfected cells. Silencing angiomotin in EPC inhibited sCD146 angiogenic effects, i.e. EPC migration, proliferation, and capacity to form capillary-like structures in Matrigel. In addition, sCD146 effects were inhibited by the angiomotin inhibitor angiostatin and competition with recombinant angiomotin. Finally, binding of sCD146 on angiomotin triggered the activation of several transduction pathways that were identified by antibody array. These results delineate a novel signaling pathway where sCD146 binds to angiomotin to stimulate a proangiogenic response. This result is important to find novel target cells of sCD146 and for the development of therapeutic strategies based on EPC in the treatment of ischemic diseases. PMID:23389031

  3. Study of serum soluble vascular cell adhesion molecule-1 levels in type 2 diabetic patients with diabetic retinopathy

    International Nuclear Information System (INIS)

    Li Fangdu; Chu Qiaomei

    2002-01-01

    To study the change and the correlation of serum soluble vascular cell adhesion molecule-1 (sV-CAM-1) levels with diabetic retinopathy in type 2 diabetic patients, serum sVCAM-1 levels were measured in duplicate by ELISA in 85 type 2 diabetic patients; fundus examination was performed by an ophthalmologist using ophthalmoscope or fundus fluorescein angiography, and the findings were graded as: no signs of diabetic retinopathy (NDR), background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). Serum sVCAM-1 levels were significantly higher in the PDR and BDR groups than those in the control and NDR groups respectively (P<0.01). NDR group showed significantly increased serum sVCAM-levels compared with control group (P<0.01). In contrast, serum sVCAM-1 levels were not related to the presence of blood glucose, serum insulin levels or known diabetic duration. Authors' results suggest that serum sVCAM-1 might be implicated in the development of the diabetic retinopathy, and could assess the severity of diabetic retinopathy. The measurement of serum sVCAM-1 levels in 2 type diabetic patients may be clinically useful for early diagnosis or treatment of diabetic retinopathy

  4. Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1 as a Biomarker in the Mouse Model of Experimental Autoimmune Myocarditis (EAM.

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    U Grabmaier

    Full Text Available 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.

  5. Multiple myeloma is affected by multiple and heterogeneous somatic mutations in adhesion- and receptor tyrosine kinase signaling molecules

    International Nuclear Information System (INIS)

    Leich, E; Weißbach, S; Klein, H-U; Grieb, T; Pischimarov, J; Stühmer, T; Chatterjee, M; Steinbrunn, T; Langer, C; Eilers, M; Knop, S; Einsele, H; Bargou, R; Rosenwald, A

    2013-01-01

    Multiple myeloma (MM) is a largely incurable plasma cell malignancy with a poorly understood and heterogeneous clinical course. To identify potential, functionally relevant somatic mutations in MM, we performed whole-exome sequencing of five primary MM, corresponding germline DNA and six MM cell lines, and developed a bioinformatics strategy that also integrated published mutational data of 38 MM patients. Our analysis confirms that identical, recurrent mutations of single genes are infrequent in MM, but highlights that mutations cluster in important cellular pathways. Specifically, we show enrichment of mutations in adhesion molecules of MM cells, emphasizing the important role for the interaction of the MM cells with their microenvironment. We describe an increased rate of mutations in receptor tyrosine kinases (RTKs) and associated signaling effectors, for example, in EGFR, ERBB3, KRAS and MAP2K2, pointing to a role of aberrant RTK signaling in the development or progression of MM. The diversity of mutations affecting different nodes of a particular signaling network appears to be an intrinsic feature of individual MM samples, and the elucidation of intra- as well as interindividual redundancy in mutations that affect survival pathways will help to better tailor targeted therapeutic strategies to the specific needs of the MM patient

  6. 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

  7. Diabetic impairment of C-kit bone marrow stem cells involves the disorders of inflammatory factors, cell adhesion and extracellular matrix molecules.

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    Tao-Sheng Li

    Full Text Available Bone marrow stem cells from diabetes mellitus patients exhibit functional impairment, but the relative molecular mechanisms responsible for this impairment are poorly understood. We investigated the mechanisms responsible for diabetes-related functional impairment of bone marrow stem cells by extensively screening the expression levels of inflammatory factors, cell cycle regulating molecules, extracellular matrix molecules and adhesion molecules. Bone marrow cells were collected from type 2 diabetic (db/db and healthy control (db/m+ mice, and c-kit+ stem cells were purified (purity>85% for experiments. Compared with the healthy control mice, diabetic mice had significantly fewer c-kit+ stem cells, and these cells had a lower potency of endothelial differentiation; however, the production of the angiogenic growth factor VEGF did not differ between groups. A pathway-focused array showed that the c-kit+ stem cells from diabetic mice had up-regulated expression levels of many inflammatory factors, including Tlr4, Cxcl9, Il9, Tgfb1, Il4, and Tnfsf5, but no obvious change in the expression levels of cell cycle molecules. Interestingly, diabetes-related alterations of the extracellular matrix and adhesion molecules were varied; Pecam, Mmp10, Lamc1, Itgb7, Mmp9, and Timp4 were up-regulated, but Col11a1, Fn1, Admts2, and Itgav were down-regulated. Some of these changes were also confirmed at the protein level by flow cytometry analysis. In conclusion, c-kit+ bone marrow stem cells from diabetic mice exhibited an extensive enhancement of inflammatory factors and disorders of the extracellular matrix and adhesion molecules. Further intervention studies are required to determine the precise role of each molecule in the diabetes-related functional impairment of c-kit+ bone marrow stem cells.

  8. Identification of an amino acid sequence motif in the cytoplasmic domain of the NCAM-140 kDa isoform essential for its neuritogenic activity

    DEFF Research Database (Denmark)

    Kolkova, K; Pedersen, N; Berezin, V

    2000-01-01

    encoding cytNCAM-140, cytNCAM-180, the constitutively active form of the mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase kinase (MEK2), and the enhanced variant of the green fluorescent protein (EGFP). EGFP expression was used for identification of transfected cells. We found...... that expression of cytNCAM-180 had no effect on NCAM-stimulated neuritogenesis, whereas expression of cytNCAM-140 strongly inhibited this process. However, if MEK2 was expressed concomitantly with cytNCAM-140, neurite outgrowth was rescued, indicating that cytNCAM-140 is involved in signaling via the Ras...

  9. 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

    with the fibroblast growth factor receptor (FGFR). A 15-amino-acid long peptide, the FG loop (FGL) peptide, that is derived from the second F3 module of NCAM has been found to activate FGFR1. We here report that the FGL peptide, when administered intranasally to newborn rats, accelerated early postnatal development...

  10. 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, Else Kirstine

    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, 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...... 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...

  11. Serum levels of tumor necrosis factor-α and soluble adhesion molecules in relation to magnetic resonance imaging results and clinical activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Millers, A.; Metra, M.; Mastina, M.; Platkajis, A.; Kukaine, R.

    2001-01-01

    One direction of research in pathogenesis of multiple sclerosis (MS) has been to identify immunological markers associated with disease activity that are capable of predicting subsequent course of disease and are sensitive to intervention by immunomodulatory therapies. Adhesion molecules and tumor necrosis factor-α of the cytokine superfamily are associated with inflammation-mediated blood-brain barrier dysfunction and demyelination in the central nervous system (CNS). This study investigates the relationship between the serum level of soluble vascular adhesion molecule-1 (sVCAM), soluble intercellular adhesion molecule-1 (alCAM), tumor necrosis factor-α (TNF-α) and magnetic resonance imaging (MRI) activity in 18 patients with relapsing-remitting (RR) MS with different clinical activity. Patients with active gadolinium (Gd)-enhanced lesions on MRI showed a higher serum level of TNF-α, sVCA-1, slCAM-1 than RR MS patients without Gd-enhanced lesions. Control individuals (n=10) without MRI abnormalities had significantly lower serum levels of the above immunological parameters. These results suggest that serum levels of TNF-α and adhesion molecules slCAM-1 in RR MS patients are correlated with Gd-enhanced MRI and disease clinical activity and that they can be used as biological markers of disease activity. The soluble form of VCAM levels in peripheral blood did not correlate with disease activity and Gd-enhanced lesions of MRI. sVCAM as an early indicator of blood-brain barrier dysfunction may also serve as marker of beneficial activity in the relapsing phase of MS course. (authors)

  12. 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.

  13. The Adhesion Molecule-Characteristic HNK-1 Carbohydrate Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish.

    Science.gov (United States)

    Ma, Liping; Shen, Hui-Fan; Shen, Yan-Qin; Schachner, Melitta

    2017-07-01

    The human natural killer cell antigen-1 (HNK-1) is functionally important in development, synaptic activity, and regeneration after injury in the nervous system of several mammalian species. It contains a sulfated glucuronic acid which is carried by neural adhesion molecules and expressed in nonmammalian species, including zebrafish, which, as opposed to mammals, spontaneously regenerate after injury in the adult. To evaluate HNK-1's role in recovery of function after spinal cord injury (SCI) of adult zebrafish, we assessed the effects of the two HNK-1 synthesizing enzymes, glucuronyl transferase and HNK-1 sulfotransferase. Expression of these two enzymes was increased at the messenger RNA (mRNA) level 11 days after injury in the brainstem nuclei that are capable of regrowth of severed axons, namely, the nucleus of medial longitudinal fascicle and intermediate reticular formation, but not at earlier time points after SCI. mRNA levels of glucuronyl transferase and sulfotransferase were increased in neurons, not only of these nuclei but also in the spinal cord caudal to the injury site at 11 days. Mauthner neurons which are not capable of regeneration did not show increased levels of enzyme mRNAs after injury. Reducing protein levels of the enzymes by application of anti-sense morpholinos resulted in reduction of locomotor recovery for glucuronyl transferase, but not for HNK-1 sulfotransferase. The combined results indicate that HNK-1 is upregulated in expression only in those neurons that are intrinsically capable of regeneration and contributes to regeneration after spinal cord injury in adult zebrafish in the absence of its sulfate moiety.

  14. [Influence of hepatocyte cell adhesion molecule on gene expression profile of human bladder transitional cell carcinoma cell line].

    Science.gov (United States)

    Wang, Qiu-ju; Lv, Chang-kun; Tao, Jia; Du, Hong-fei; Fan, Yan-ru; Song, Xue-dong; Luo, Chun-li

    2013-04-01

    To investigate the changes of gene expression file in transitional cell carcinoma of bladder after hepatocyte cell adhesion molecule(hepaCAM) overexpression. Affymetrix Human Genome U133 Plus 2.0 Array was used to investigate the changes of gene expression profile between adenovirus-green fluorescent protein(GFP) -hepaCAM group and GFP group in transitional cell carcinoma of bladder EJ cells.Significant Analysis of Microarray(SAM) was used to screen the differentially expressed genes, DAVID software was used to conduct gene ontology analysis and wikiPathway analysis based on the differentially expressed genes. Reverse transcription-polymerase chain reaction and Western blot were applied to verify microarray data. Compared with the GFP group, a total of 2469 genes were up-regulated or down-regulated by more than 2 times in the GFP-hepaCAM group. Among these genes, 1602 genes were up-regulated and 867 were down-regulated.Most of the differentially expressed genes were involved in the function of cell proliferation and cell cycle regulation. The mRNA expressions of nibrin, liver kinase B1, and cyclin D1 detected by reverse transcription-polymerase chain reaction in three different bladder cancer cell lines were consistent with the microarray data.The protein expressions of nibrin and liver kinase B1 in these three cell lines measured by Western blot were consistent with the mRNA expression. HepaCAM can alter the gene expression profile of bladder cancer EJ cells. The well-known anti-tumor effect of hepaCAM may be mediated by regulating the gene expression via multiple pathways.

  15. 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.

  16. The neuroplastin adhesion molecules are accessory proteins that chaperone the monocarboxylate transporter MCT2 to the neuronal cell surface.

    Directory of Open Access Journals (Sweden)

    Marieangela C Wilson

    Full Text Available The neuroplastins np65 and np55 are two synapse-enriched immunoglobulin (Ig superfamily adhesion molecules that contain 3 and 2 Ig domains respectively. Np65 is implicated in long term, activity dependent synaptic plasticity, including LTP. Np65 regulates the surface expression of GluR1 receptor subunits and the localisation of GABA(A receptor subtypes in hippocampal neurones. The brain is dependent not only on glucose but on monocarboxylates as sources of energy. The. monocarboxylate transporters (MCTs 1-4 are responsible for the rapid proton-linked translocation of monocarboxylates including pyruvate and lactate across the plasma membrane and require association with either embigin or basigin, proteins closely related to neuroplastin, for plasma membrane expression and activity. MCT2 plays a key role in providing lactate as an energy source to neurons.Here we use co-transfection of neuroplastins and monocarboxylate transporters into COS-7 cells to demonstrate that neuroplastins can act as ancillary proteins for MCT2. We also show that Xenopus laevis oocytes contain endogenous neuroplastin and its knockdown with antisense RNA reduces the surface expression of MCT2 and associated lactate transport. Immunocytochemical studies show that MCT2 and the neuroplastins are co-localised in rat cerebellum. Strikingly neuroplastin and MCT2 are enriched in the same parasagittal zebrin II-negative stripes.These data strongly suggest that neuroplastins act as key ancillary proteins for MCT2 cell surface localisation and activity in some neuronal populations, thus playing an important role in facilitating the uptake of lactate for use as a respiratory fuel.

  17. Immunohistochemical expression of epithelial cell adhesion molecule (EpCAM) in mucoepidermoid carcinoma compared to normal salivary gland tissues.

    Science.gov (United States)

    Kamal, Noura M; Salem, Hend M; Dahmoush, Heba M

    2017-07-01

    Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which displays biological, histological and clinical diversity thus representing a challenge for its diagnosis and management. Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein identified as a tumor specific antigen due to its frequent overexpression in the majority of epithelial carcinomas and its correlation with prognosis. It is considered to be a promising biomarker used as a therapeutic target already in ongoing clinical trials. The purpose of this study was to investigate the pattern, cellular characterization and level of EpCAM expression in MEC and demonstrate its correlation with histologic grading which may benefit future clinical trials using EpCAM targeted therapy. 48 specimens (12 normal salivary gland tissue and 36 MEC) were collected and EpCAM membranous expression was evaluated by immunohistochemistry. Total immunoscore (TIS) was evaluated, the term 'EpCAM overexpression' was given for tissues showing a total immunoscore >4. A highly significant difference was observed between TIS percent values in control and different grades of MEC (p<0.001). High grade MEC (HG-MEC) was the highest EpCAM expressor. In addition, EpCAM expression pattern differed among the different grades. EpCAM expression was detected in MEC, and its overexpression correlated with increasing the histological grade. The diffuse membranous expression in HG-MEC could be of diagnostic value in relation to the patchy expression observed in both low grade and intermediate grade MEC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Adhesion molecule expression and function of primary endothelial cells in benign and malignant tissues correlates with proliferation.

    Directory of Open Access Journals (Sweden)

    Wolfgang Sievert

    Full Text Available BACKGROUND: Comparative analysis of the cellular biology of the microvasculature in different tissues requires the availability of viable primary endothelial cells (ECs. This study describes a novel method to isolate primary ECs from healthy organs, repair blastemas and tumors as examples of non-proliferating and proliferating benign and malignant tissues and their functional characterization. METHODOLOGY/PRINCIPAL FINDINGS: Single cell suspensions from hearts, lungs, repair blastemas and tumors were incubated consecutively with an anti-CD31 antibody and magnetic micro-beads, coupled to a derivative of biotin and streptavidin, respectively. Following magnetic bead separation, CD31-positive ECs were released by biotin-streptavidin competition. In the absence of micro-beads, ECs became adherent to plastic surfaces. ECs from proliferating repair blastemas and tumors were larger and exhibited higher expression densities of CD31, CD105 and CD102 compared to those from non-proliferating normal tissues such as heart and lung. The expression density of CD34 was particularly high in tumor-derived ECs, and that of CD54 and CD144 in ECs of repair blastemas. Functionally, ECs of non-proliferating and proliferating tissues differed in their capacity to form tubes in matrigel and to align under flow conditions. CONCLUSIONS/SIGNIFICANCE: This method provides a powerful tool to generate high yields of viable, primary ECs of different origins. The results suggest that an altered expression of adhesion molecules on ECs in proliferating tissues contribute to loss of EC function that might cause a chaotic tumor vasculature.

  19. Biologic role of activated leukocyte cell adhesion molecule overexpression in breast cancer cell lines and clinical tumor tissue.

    Science.gov (United States)

    Hein, Sibyll; Müller, Volkmar; Köhler, Nadine; Wikman, Harriet; Krenkel, Sylke; Streichert, Thomas; Schweizer, Michaela; Riethdorf, Sabine; Assmann, Volker; Ihnen, Maike; Beck, Katrin; Issa, Rana; Jänicke, Fritz; Pantel, Klaus; Milde-Langosch, Karin

    2011-09-01

    The activated leukocyte cell adhesion molecule (ALCAM) is overexpressed in many mammary tumors, but controversial results about its role and prognostic impact in breast cancer have been reported. Therefore, we evaluated the biologic effects of ALCAM expression in two breast cancer cell lines and a larger cohort of mammary carcinomas. By stable transfections, MCF7 cells with ALCAM overexpression and MDA-MB231 cells with reduced ALCAM levels were generated and analyzed in functional assays and cDNA microarrays. In addition, an immunohistochemical study on 347 patients with breast cancer with long-term follow-up and analysis of disseminated tumor cells (DTCs) was performed. In both cell lines, high ALCAM expression was associated with reduced cell motility. In addition, ALCAM silencing in MDA-MB231 cells resulted in lower invasive potential, whereas high ALCAM expression was associated with increased apoptosis in both cell lines. Among genes which were differentially expressed in clones with altered ALCAM expression, there was an overlap of 15 genes between both cell lines, among them cathepsin D, keratin 7, gelsolin, and ets2 whose deregulation was validated by western blot analysis. In MDA-MB231 cells, we observed a correlation with VEGF expression which was validated by enzyme-linked immuno sorbent assay (ELISA). Our IHC results on primary breast carcinomas showed that ALCAM expression was associated with an estrogen receptor-positive phenotype. In addition, strong ALCAM immunostaining correlated with nodal involvement and the presence of tumor cells in bone marrow. By Kaplan-Meier analysis, strong ALCAM expression in ductal carcinomas correlated with shorter recurrence-free intervals (P=0.048) and overall survival (OAS, P=0.003). Our results indicate that the biologic role of ALCAM in breast cancer is complex, but overexpression might be relevant for outcome in ductal carcinomas.

  20. Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.

    Directory of Open Access Journals (Sweden)

    Diana J M van den Wollenberg

    Full Text Available Mammalian Reovirus is a double-stranded RNA virus with a distinctive preference to replicate in and lyse transformed cells. On that account, Reovirus type 3 Dearing (T3D is clinically evaluated as oncolytic agent. The therapeutic efficacy of this approach depends in part on the accessibility of the reovirus receptor Junction Adhesion Molecule-A (JAM-A on the target cells. Here, we describe the isolation and characterization of reovirus T3D mutants that can infect human tumor cells independent of JAM-A. The JAM-A-independent (jin mutants were isolated on human U118MG glioblastoma cells, which do not express JAM-A. All jin mutants harbour mutations in the S1 segments close to the region that encodes the sialic acid-binding pocket in the shaft of the spike protein. In addition, two of the jin mutants encode spike proteins with a Q336R substitution in their head domain. The jin mutants can productively infect a wide range of cell lines that resist wt reovirus T3D infection, including chicken LMH cells, hamster CHO cells, murine endothelioma cells, human U2OS and STA-ET2.1 cells, but not primary human fibroblasts. The jin-mutants rely on the presence of sialic-acid residues on the cell surface for productive infection, as is evident from wheat germ agglutinin (WGA inhibition experiments, and from the jin-reovirus resistance of CHO-Lec2 cells, which have a deficiency of sialic-acids on their glycoproteins. The jin mutants may be useful as oncolytic agents for use in tumors in which JAM-A is absent or inaccessible.

  1. High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor

    DEFF Research Database (Denmark)

    Lathia, Justin D; Li, Meizhang; Sinyuk, Maksim

    2014-01-01

    Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow...... cytometry screen on patient-derived glioblastoma (GBM) cells and identified junctional adhesion molecule A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function, and JAM-A expression was reduced in normal...... brain versus GBM. Targeting JAM-A compromised the self-renewal of CSCs. JAM-A expression negatively correlated to GBM patient prognosis. Our results demonstrate that GBM-targeting strategies can be identified through screening adhesion receptors and JAM-A represents a mechanism for niche-driven CSC...

  2. Quantitative proteomic profiling identifies DPYSL3 as pancreatic ductal adenocarcinoma-associated molecule that regulates cell adhesion and migration by stabilization of focal adhesion complex.

    Directory of Open Access Journals (Sweden)

    Takeo Kawahara

    Full Text Available Elucidation of how pancreatic cancer cells give rise to distant metastasis is urgently needed in order to provide not only a better understanding of the underlying molecular mechanisms, but also to identify novel targets for greatly improved molecular diagnosis and therapeutic intervention. We employed combined proteomic technologies including mass spectrometry and isobaric tags for relative and absolute quantification peptide tagging to analyze protein profiles of surgically resected human pancreatic ductal adenocarcinoma tissues. We identified a protein, dihydropyrimidinase-like 3, as highly expressed in human pancreatic ductal adenocarcinoma tissues as well as pancreatic cancer cell lines. Characterization of the roles of dihydropyrimidinase-like 3 in relation to cancer cell adhesion and migration in vitro, and metastasis in vivo was performed using a series of functional analyses, including those employing multiple reaction monitoring proteomic analysis. Furthermore, dihydropyrimidinase-like 3 was found to interact with Ezrin, which has important roles in cell adhesion, motility, and invasion, while that interaction promoted stabilization of an adhesion complex consisting of Ezrin, c-Src, focal adhesion kinase, and Talin1. We also found that exogenous expression of dihydropyrimidinase-like 3 induced activating phosphorylation of Ezrin and c-Src, leading to up-regulation of the signaling pathway. Taken together, the present results indicate successful application of combined proteomic approaches to identify a novel key player, dihydropyrimidinase-like 3, in pancreatic ductal adenocarcinoma tumorigenesis, which may serve as an important biomarker and/or drug target to improve therapeutic strategies.

  3. Quantitative proteomic profiling identifies DPYSL3 as pancreatic ductal adenocarcinoma-associated molecule that regulates cell adhesion and migration by stabilization of focal adhesion complex.

    Science.gov (United States)

    Kawahara, Takeo; Hotta, Naoe; Ozawa, Yukiko; Kato, Seiichi; Kano, Keiko; Yokoyama, Yukihiro; Nagino, Masato; Takahashi, Takashi; Yanagisawa, Kiyoshi

    2013-01-01

    Elucidation of how pancreatic cancer cells give rise to distant metastasis is urgently needed in order to provide not only a better understanding of the underlying molecular mechanisms, but also to identify novel targets for greatly improved molecular diagnosis and therapeutic intervention. We employed combined proteomic technologies including mass spectrometry and isobaric tags for relative and absolute quantification peptide tagging to analyze protein profiles of surgically resected human pancreatic ductal adenocarcinoma tissues. We identified a protein, dihydropyrimidinase-like 3, as highly expressed in human pancreatic ductal adenocarcinoma tissues as well as pancreatic cancer cell lines. Characterization of the roles of dihydropyrimidinase-like 3 in relation to cancer cell adhesion and migration in vitro, and metastasis in vivo was performed using a series of functional analyses, including those employing multiple reaction monitoring proteomic analysis. Furthermore, dihydropyrimidinase-like 3 was found to interact with Ezrin, which has important roles in cell adhesion, motility, and invasion, while that interaction promoted stabilization of an adhesion complex consisting of Ezrin, c-Src, focal adhesion kinase, and Talin1. We also found that exogenous expression of dihydropyrimidinase-like 3 induced activating phosphorylation of Ezrin and c-Src, leading to up-regulation of the signaling pathway. Taken together, the present results indicate successful application of combined proteomic approaches to identify a novel key player, dihydropyrimidinase-like 3, in pancreatic ductal adenocarcinoma tumorigenesis, which may serve as an important biomarker and/or drug target to improve therapeutic strategies.

  4. 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.

  5. 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.

    Science.gov (United States)

    Shih, Mei Fen; Cherng, Jong Yuh

    2014-07-18

    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.

  6. 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

  7. MEK inhibitors, novel anti-adhesive molecules, reduce sickle red blood cell adhesion in vitro and in vivo, and vasoocclusion in vivo.

    Science.gov (United States)

    Zennadi, Rahima

    2014-01-01

    In sickle cell disease, sickle erythrocyte (SSRBC) interacts with endothelial cells, leukocytes, and platelets, and activates coagulation and inflammation, promoting vessel obstruction, which leads to serious life-threatening complications, including acute painful crises and irreversible damage to multiple organs. The mitogen-activated protein kinase, ERK1/2, is abnormally activated in SSRBCs. However, the therapeutic potential of SSRBC ERK1/2 inactivation has never been investigated. I tested four different inhibitors of MEK1/2 (MEK), the kinase that activates ERK1/2, in a model of human SSRBC adhesion to TNFα-activated endothelial cells (ECs). SSRBC MEK inhibition abrogated adhesion to non-activated and TNFα-activated ECs to levels below baseline SSRBC adhesion to non-activated ECs in vitro. SSRBC MEK inhibition also prevented SSRBCs from activating naïve neutrophils to adhere to endothelium. To determine the effect of MEK inhibitors on SSRBC adherence in vivo, sham-treated or MEK inhibitor-treated SSRBCs were infused to nude mice previously treated with TNFα. Sham-treated SSRBCs displayed marked adhesion and occlusion of enflamed vessels, both small and large. However, SSRBC treatment with MEK inhibitors ex vivo showed poor SSRBC adhesion to enflamed vessels with no visible vasoocclusion in vivo. In addition, MEK inhibitor treatment of SSRBCs reduced SSRBC organ trapping and increased the number of SSRBCs circulating in bloodstream. Thus, these data suggest that SSRBC ERK1/2 plays potentially a critical role in sickle pathogenesis, and that MEK inhibitors may represent a valuable intervention for acute sickle cell crises.

  8. Borrelia burgdorferi upregulates the adhesion molecules E-selectin, P-selectin, ICAM-1 and VCAM-1 on mouse endothelioma cells in vitro.

    Science.gov (United States)

    Böggemeyer, E; Stehle, T; Schaible, U E; Hahne, M; Vestweber, D; Simon, M M

    1994-06-01

    In order to obtain more information on processes leading to Borrelia burgdorferi-induced inflammation in the host, we have developed an in vitro model to study the upregulation of cell surface expression of adhesion molecules on endothelial cells by spirochetes. A mouse endothelioma cell line, derived from brain capillaries, bEnd3, was used as indicator population. bEnd3 cells were incubated with preparations of viable, inactivated or sonicated spirochetes and the expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 was monitored by immunocytochemistry and quantified by cell surface ELISA. We show that all three spirochetal preparations are able to upregulate cell surface expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 on bEnd 3 cells in a dose-dependent manner. The kinetics of cell surface expression of the individual adhesion molecules in the presence of Borrelia burgdorferi showed maxima at about 50 h of incubation or later; this was distinct from results obtained with sonicated-preparations of Escherichia coli bacteria or with enterobacterial LPS where peak expression was observed between 4 h and 16 h. The fact that Borrelia burgdorferi does not contain conventional LPS suggests that the mode of induction of adhesion molecules on endothelial cells is influenced by the phenotype of bacteria. At the peak of spirochete-induced cell surface expression of adhesion molecules (approximately 50 h), bEnd3 cells were found to bind cells of a VLA-4+ B lymphoma line (L1-2) much more efficiently than untreated control cells. The binding of L1-2 cells to presensitized bEnd3 cells was significantly inhibited (more than 75%) in the presence of monoclonal antibodies to both VLA-4 and its endothelial counterreceptor VCAM-1. These findings demonstrate that Borrelia burgdorferi organisms are able to induce functionally active adhesion molecules on endothelial cells in vitro and suggest that E-selectin, P-selectin, ICAM-1 and VCAM-1 play an important role in the

  9. 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...

  10. Effects of Chinese yellow wine on nitric oxide synthase and intercellular adhesion molecule-1 expressions in rat vascular endothelial cells.

    Science.gov (United States)

    Zhao, Fei; Ji, Zheng; Chi, Jufang; Tang, Weiliang; Zhai, Xiaoya; Meng, Liping; Guo, Hangyuan

    2016-02-01

    The objective of this study was to determine similarities in the effect of yellow wine as compared to statin and the possibility that yellow wine inhibits tumour necrosis factor-α (TNF-α)-induced nitric oxide (NO) synthesis, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) in cultured rat vascular endothelial cells (VECs). We isolated VECs, and cultivated and purified Sprague Dawley (SD) rat thoracic aortas in vitro. We selected the optimal wine concentration using clonogenic and MTT assays to measure cell survival. Next, we divided the cells into 9 groups: (1) control, (2) TNF-α, (3) TNF-α + rosuvastatin (10 μmol/L), (4) TNF-α + ethanol 0.5%, (5) TNF-α + yellow wine 0.5%, (6) TNF-α + ethanol 1.0%, (7) TNF-α + yellow wine 1.0%, (8) TNF-α + ethanol 1.5%, and (9) TNF-α + yellow wine 1.5% and they were given the corresponding treatment for 24 h. We determined NO production with nitrate reductase. We then measured eNOS activity, and detected eNOS, iNOS, and ICAM-1 protein levels by Western blotting. Compared with the TNF-α group, NO production, eNOS activity, and eNOS protein expression in the rosuvastatin, and yellow wine 1.0%, and 1.5% groups were significantly increased. Protein expression of iNOS and ICAM-1 in the rosuvastatin, yellow wine 1.0%, and 1.5% groups were significantly decreased. Compared with the rosuvastatin group, eNOS, iNOS, and ICAM-1 protein expression in the yellow wine (0.5% -1.5%) groups were significantly different. Treatment with yellow wine increased NO production, eNOS activity, and eNOS protein expression, which decreases iNOS and ICAM-1 protein expression. We conclude that yellow wine may have similar beneficial effects as rosuvastatin on the cardiovascular system. These effects may be attributed to their anti-atherosclerotic actions.

  11. 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.

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

    DEFF Research Database (Denmark)

    Kolkova, K; Novitskaya, V; Pedersen, N

    2000-01-01

    transfected with expression plasmids encoding constitutively active forms of Ras, Raf, MAP kinase kinases MEK1 and 2, dominant negative forms of Ras and Raf, and the FAK-related nonkinase. Alternatively, PC12-E2 cells were submitted to treatment with antibodies to the fibroblast growth factor (FGF) receptor......, inhibitors of the nonreceptor tyrosine kinase p59(fyn), PLC, PKC and MEK and an activator of PKC, phorbol-12-myristate-13-acetate (PMA). MEK2 transfection rescued cells treated with all inhibitors. The same was found for PMA treatment, except when cells concomitantly were treated with the MEK inhibitor....... Arachidonic acid rescued cells treated with antibodies to the FGF receptor or the PLC inhibitor, but not cells in which the activity of PKC, p59(fyn), FAK, Ras, or MEK was inhibited. Interaction of NCAM with a synthetic NCAM peptide ligand, known to induce neurite outgrowth, was shown to stimulate...

  13. Effect of irradiation-induced intercellular adhesion molecule-1 expression on natural killer cell-mediated cytotoxicity toward human cancer cells.

    Science.gov (United States)

    Jeong, Jae-Uk; Uong, Tung Nguyen Thanh; Chung, Woong-Ki; Nam, Taek-Keun; Ahn, Sung-Ja; Song, Ju-Young; Kim, Sang-Ki; Shin, Dong-Jun; Cho, Eugene; Kim, Kyoung Won; Cho, Duck; Yoon, Mee Sun

    2018-03-20

    Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity. Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human peripheral blood mononuclear cells was performed by co-culture with irradiated K562 cells. The related adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked immunosorbent assay was used to detect interferon-γ (IFN-γ), and WST-8 assays were performed to check NK cell cytotoxicity. Finally, blocking assays were performed using monoclonal antibodies against ICAM-1 or LFA-1. LFA-1 expression increased on NK cells after expansion (P cytotoxicity increased after irradiation of HL60 (P cytotoxicity against irradiated SKBR-3 (P cytotoxicity against irradiated HL60 (P cytotoxicity. Therefore, irradiation combined with NK cell therapy may improve the antitumor effects of NK cells. Copyright © 2018. Published by Elsevier Inc.

  14. Enoxaparin reduces H2O2-induced activation of human endothelial cells by a mechanism involving cell adhesion molecules and nuclear transcription factors.

    Science.gov (United States)

    Manduteanu, Ileana; Dragomir, Elena; Voinea, Manuela; Capraru, Monica; Simionescu, Maya

    2007-01-01

    There are data that document the anti-inflammatory effect of enoxaparin (EP) and its possible antioxidant potential. This study was designed to search for the antioxidant mechanism(s) of EP directly on endothelial cells exposed to an oxidant stimulus. For this purpose cultured human endothelial cells were exposed to nontoxic concentrations of hydrogen peroxide in the presence or absence of EP, and the adhesion of monocytes, the expression of cell adhesion molecules and transcription factors possibly involved in the process were tested. Adhesion assays, ELISA and Western blot analysis revealed that EP reduced monocyte adhesion, ICAM-1 and P-selectin expression, decreased the nuclear levels of c-Jun and p65 proteins, and diminished the phosphorylation of c-Jun protein, MAPK p38 and JNK. Together, the data demonstrate the antioxidant effect of EP and the involvement of ICAM-1, P-selectin, MAPK p38, JNK and the transcription factors NF-kappaB and AP-1 in the mechanism of action of this drug. (c) 2007 S. Karger AG, Basel.

  15. 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...

  16. Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial.

    Science.gov (United States)

    Chiva-Blanch, Gemma; Urpi-Sarda, Mireia; Llorach, Rafael; Rotches-Ribalta, Maria; Guillén, Marisa; Casas, Rosa; Arranz, Sara; Valderas-Martinez, Palmira; Portoles, Olga; Corella, Dolores; Tinahones, Francisco; Lamuela-Raventos, Rosa M; Andres-Lacueva, Cristina; Estruch, Ramon

    2012-02-01

    Few clinical studies have focused on the alcohol-independent cardiovascular effects of the phenolic compounds of red wine (RW). We aimed to evaluate the effects of ethanol and phenolic compounds of RW on the expression of inflammatory biomarkers related to atherosclerosis in subjects at high risk of cardiovascular disease. Sixty-seven high-risk, male volunteers were included in a randomized, crossover consumption trial. After a washout period, all subjects received RW (30 g alcohol/d), the equivalent amount of dealcoholized red wine (DRW), or gin (30 g alcohol/d) for 4 wk. Before and after each intervention period, 7 cellular and 18 serum inflammatory biomarkers were evaluated. Alcohol increased IL-10 and decreased macrophage-derived chemokine concentrations, whereas the phenolic compounds of RW decreased serum concentrations of intercellular adhesion molecule-1, E-selectin, and IL-6 and inhibited the expression of lymphocyte function-associated antigen 1 in T lymphocytes and macrophage-1 receptor, Sialil-Lewis X, and C-C chemokine receptor type 2 expression in monocytes. Both ethanol and phenolic compounds of RW downregulated serum concentrations of CD40 antigen, CD40 ligand, IL-16, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1. The results suggest that the phenolic content of RW may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of RW may modulate soluble inflammatory mediators in high-risk patients. The trial was registered in the International Standard Randomized Controlled Trial Number Register at http://www.isrctn.org/ as ISRCTN88720134.

  17. 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

    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...... protonated surface. The results demonstrate that the alumina surface at pH 3 has a higher affinity for inorganic cations than for -COO(H) or -C5H5N(H+), in spite of the known positive surface charge of α-alumina {0001} wafers. These results demonstrate that solution salinity plays an important role...

  18. Rhenium-188-labeled anti-neural cell adhesion molecule antibodies with 2-iminothiolane modification for targeting small-cell lung cancer.

    Science.gov (United States)

    Hosono, M N; Hosono, M; Mishra, A K; Faivre-Chauvet, A; Gautherot, E; Barbet, J; Knapp, F F; Chatal, J F

    2000-06-01

    We have evaluated the potential of 188Re-labeled monoclonal antibodies (MAbs) modified with 2-iminothiolane (2IT) for targeting small-cell lung cancer (SCLC). Radiolabeled MAbs NK1NBL1 and C218 recognizing neural cell adhesion molecule were injected i.v. into athymic mice inoculated with human SCLC tumors, and the biodistribution was examined. NK1NBL1 localized in the tumors better than C218. 188Re-labeled MAbs cleared from the blood faster than 125I-labeled counterparts, resulting in higher tumor-to-blood ratios. In conclusion, the 188Re-labeled MAbs are attractive candidates for imaging and therapy of SCLC.

  19. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Directory of Open Access Journals (Sweden)

    Kelsey Roe

    Full Text Available Characterizing the mechanisms by which West Nile virus (WNV causes blood-brain barrier (BBB disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE. Infection with WNV (NY99 strain significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1 did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101 strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  20. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Science.gov (United States)

    Roe, Kelsey; Orillo, Beverly; Verma, Saguna

    2014-01-01

    Characterizing the mechanisms by which West Nile virus (WNV) causes blood-brain barrier (BBB) disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs) in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE). Infection with WNV (NY99 strain) significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1) did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101) strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  1. Synaptic Cell Adhesion

    OpenAIRE

    Missler, Markus; Südhof, Thomas C.; Biederer, Thomas

    2012-01-01

    Chemical synapses are asymmetric intercellular junctions that mediate synaptic transmission. Synaptic junctions are organized by trans-synaptic cell adhesion molecules bridging the synaptic cleft. Synaptic cell adhesion molecules not only connect pre- and postsynaptic compartments, but also mediate trans-synaptic recognition and signaling processes that are essential for the establishment, specification, and plasticity of synapses. A growing number of synaptic cell adhesion molecules that inc...

  2. C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity.

    Science.gov (United States)

    Svajger, Urban; Anderluh, Marko; Jeras, Matjaz; Obermajer, Natasa

    2010-10-01

    The dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II C-type lectin whose expression is restricted to the most potent antigen-presenting cells (APCs), the dendritic cells (DCs). In recent years, DC-SIGN has gained an exponential increase in attention because of its involvement in multiple aspects of immune function. Besides being an adhesion molecule, particularly in binding ICAM-2 and ICAM-3, it is also crucial in recognizing several endogenous and exogenous antigens. Additionally, the intracellular domain of DC-SIGN includes molecular motifs, which enable the activation of signal transduction pathways involving Raf-1 and subsequent modulation of DC-maturation status, through direct modification of nuclear factor Nf-kappaB in DCs. Upon DC-SIGN engagement by mannose- or fucose-containing oligosaccharides, the latter leads to a tailored Toll-like receptor signalling, resulting in an altered DC-cytokine profile and skewing of Th1/Th2 responses. In this article, we will discuss recent advances on a broad perspective concerning DC-SIGN structure, signalling and immune function. Copyright 2010 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Novel association of soluble intercellular adhesion molecule 1 and soluble P-selectin with the ABO blood group in a Chinese population.

    Science.gov (United States)

    Zhang, Wenjing; Xu, Qun; Zhuang, Yunlong; Chen, Yuanfeng

    2016-08-01

    Recent studies have reported that the ABO gene can affect circulating expression levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble P-selectin (sP-selectin) in Caucasians. However, several factors may affect the association, including the distribution and variations of the ABO gene, ethnic diversity and the inflammatory response status. The aim of the present study was to investigate this issue in Asian subjects of various blood groups. A total of 800 blood samples were randomly selected from healthy blood donors. The ABO blood groups were examined using standard serological tests, and ABO genotypes of group A and group AB specimens were analyzed. Plasma concentrations of sICAM-1 and sP-selectin were detected by standard enzyme-linked immunosorbent assays. In healthy Chinese individuals, blood group A was detected to be significantly associated with lower circulating expression levels of sICAM-1 and sP-selectin, compared with group O. Individuals with ≥1 A1 allele had significantly lower expression levels of sICAM-1 and sP-selectin compared with all other ABO groups. The data indicate the significant association of ABO blood group antigens with sICAM-1 and sP-selectin expression levels in a healthy Chinese population, independent of the specific variations and distributions of ABO blood groups among ethnic populations. This result provides evidence for the previously unidentified role of ABO blood group antigens in the regulation of the inflammatory adhesion process. Accordingly, it can be proposed that ABO blood groups may require consideration when soluble adhesion molecules are identified as predictors for cardiovascular disease.

  6. Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

    Directory of Open Access Journals (Sweden)

    Sarah L Appleby

    Full Text Available Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+ population of non-adherent endothelial forming cells (naEFCs which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38 together with mature endothelial cell markers (VEGFR2, CD144 and CD31. These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8 or myeloid markers (CD11b and CD14 which distinguishes them from 'early' endothelial progenitor cells (EPCs. Functional studies demonstrated that these naEFCs (i bound Ulex europaeus lectin, (ii demonstrated acetylated-low density lipoprotein uptake, (iii increased vascular cell adhesion molecule (VCAM-1 surface expression in response to tumor necrosis factor and (iv in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs. Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

  7. Junctional adhesion molecule A: expression in the murine epididymal tract and accessory organs and acquisition by maturing sperm.

    Science.gov (United States)

    Wu, Kathie Z; Li, Kun; Galileo, Deni S; Martin-DeLeon, Patricia A

    2017-02-10

    Is junctional adhesion molecule A (JAM-A), a sperm protein essential for normal motility, expressed in the murine post-testicular pathway and involved in sperm maturation? JAM-A is present in the prostate and seminal vesicles and in all three regions of the epididymis where it is secreted in epididymosomes in the luminal fluid and can be delivered to sperm in vitro. JAM-A shares with the plasma membrane Ca2+ATPase 4 (PMCA4, the major Ca2+ efflux pump in murine sperm) a common interacting partner, CASK (Ca2+/CaM-dependent serine kinase). JAM-A, like PMCA4, plays a role in Ca2+ regulation, since deletion of Jam-A results in significantly elevated intracellular Ca2+ levels and reduced sperm motility. Recently, PMCA4 was reported to be expressed in the epididymis and along with CASK was shown to be in a complex on epididymosomes where it was transferred to sperm. Because of the association of JAM-A with CASK in sperm and because of the presence of PMCA4 and CASK in the epididymis, the present study was performed to determine whether JAM-A is expressed in the epididymis and delivered to sperm during their maturation. The epididymides, prostate and seminal vesicles were collected from sexually mature C57BL/6J and Institute for Cancer Research mice and antibodies specific for JAM-A and Ser285 -phosphorylated JAM-A (pJAM-A) were used for the analysis. Tissues, sperm and epididymal luminal fluid (ELF) were studied. Epididymosomes were also isolated for study. Caput and caudal sperm were co-incubated with ELF individually to determine their abilities to acquire JAM-A in vitro. Sections of all three regions of the epididymis were subjected to indirect immunofluorescence analysis. Epididymal tissues, fluid, sperm, prostate and seminal vesicle tissues were analyzed for JAM-A and/or pJAM-A via western blotting analysis. The relative amounts of JAM-A and pJAM-A among epididymal tissues, ELF and sperm were detected by western blot via quantification of band intensities

  8. Impact of the NCAM derived mimetic peptide plannexin on the acute cellular consequences of a status epilepticus

    DEFF Research Database (Denmark)

    Zellinger, Christina; Hadamitzky, Martin; Bock, Elisabeth

    2011-01-01

    Plannexin represents a NCAM-derived peptide mimicking trans-homophilic NCAM interaction, which proved to exert neuroprotective effects in vitro. The effect of plannexin was evaluated in a rat status epilepticus model. As expected, prolonged seizure activity resulted in a pronounced cell loss in h...

  9. Direct demonstration of NCAM cis-dimerization and inhibitory effect of palmitoylation using the BRET2 technique

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Grunnet, Lars Groth; Lundh, Morten

    2011-01-01

    , cis-dimerization in living cells has not been shown directly and the role of the cytoplasmic part in NCAM dimerization is poorly understood. Here, we used the bioluminescence resonance energy transfer (BRET(2)) technique to directly demonstrate that full-length NCAM cis-homodimerizes in living cells...

  10. Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules.

    Science.gov (United States)

    Costa, Vivian Vasconcelos; Ye, Weijian; Chen, Qingfeng; Teixeira, Mauro Martins; Preiser, Peter; Ooi, Eng Eong; Chen, Jianzhu

    2017-08-01

    Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo , identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control

  11. Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) in scleroderma skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Deleuran, Mette; Heickendorff, Lene

    1998-01-01

    In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin, and to compare their levels to concentrations measured in plasma and clinical parameters, we examined suction blister fluid and plasma...... from 13 patients with systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in both plasma and suction blister fluid from...... systemic sclerosis patients compared with healthy volunteers. ICAM-1 was localized to vessels and perivascular mononuclear infiltrates by immunohistochemical methods. IL-2R was expressed by CD3-positive cells. The elevated levels of sICAM-1 and sIL-2R in suction blister fluid point towards activation...

  12. Rhenium-188-labeled anti-neural cell adhesion molecule antibodies with 2-iminothiolane modification for targeting small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hosono, Masako N. [Osaka City Univ. (Japan); Hosono, Makoto; Mishra, A.K.; Faivre-Chauvet, A.; Gautherot, E.; Barbet, J.; Knapp, F.F.R. Jr; Chatal, J.F.

    2000-06-01

    We have evaluated the potential of {sup 188}Re-labeled monoclonal antibodies (MAbs) modified with 2-iminothiolane (2IT) for targeting small-cell lung cancer (SCLC). Radiolabeled MAbs NK1NBL1 and C218 recognizing neural cell adhesion molecule were injected i.v. into athymic mice inoculated with human SCLC tumors, and the biodistribution was examined. NK1NBL1 localized in the tumors better than C218. {sup 188}Re-labeled MAbs cleared from the blood faster than {sup 125}I-labeled counterparts, resulting in higher tumor-to-blood ratios. In conclusion, the {sup 188}Re-labeled MAbs are attractive candidates for imaging and therapy of SCLC. (author)

  13. A study of macrophages, macrophage-related cells, and endothelial adhesion molecules in recurrent aphthous ulcers in HIV-positive patients.

    Science.gov (United States)

    Regezi, J A; Macphail, L A; Richards, D W; Greenspan, J S

    1993-12-01

    The purpose of this immunohistochemical study was to investigate the presence and distribution of macrophages (CD11c+ and CD68+) and macrophage-related dendritic cells (factor XIIIa+ and CD36+) in early and late aphthous ulcers associated with HIV infection. To substantiate a mechanism by which these cells may move from the vascular compartment to tissue spaces, we also investigated expression of ELAM (endothelial leukocyte adhesion molecule), ICAM-1 (intercellular adhesion molecule), and CD18 (leukocyte function antigen). Numerous CD11c+ and CD68+ macrophages were seen in early lesions, though larger numbers of CD68+ cells were present in older lesions. No significant increases in factor XIIIa+ dendrocytes were seen in either early or late lesions, though dendrocytes appeared enlarged. CD36+ cells and CD18+ leukocytes were more numerous in early than in late aphthous ulcers. ELAM and ICAM expression was most intense on endothelial cells in early aphthous ulcers, with staining intensity fading toward the lesion periphery. Control specimens showed weaker ELAM and ICAM staining than did the ulcer specimens. Keratinocytes did not express ICAM. By virtue of their numbers, macrophages and macrophage subtypes appear to have a significant role in both the early and late stages of this disease. Although factor XIIIa-expressing dendrocytes may not have been more numerous in the ulcers, they appeared to be "activated" because of their prominence in the lesions and their occasional co-expression of CD68 antigen (KP1+). They may have a minor role in antigen processing, phagocytosis, and fibroplasia. ELAM and ICAM expression by endothelial cells provides a mechanism by which macrophages and other leukocytes can be recruited to the site of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. West Nile virus infection modulates human brain microvascular endothelial cells tight junction proteins and cell adhesion molecules: Transmigration across the in vitro blood-brain barrier.

    Science.gov (United States)

    Verma, Saguna; Lo, Yeung; Chapagain, Moti; Lum, Stephanie; Kumar, Mukesh; Gurjav, Ulziijargal; Luo, Haiyan; Nakatsuka, Austin; Nerurkar, Vivek R

    2009-03-15

    Neurological complications such as inflammation, failure of the blood-brain barrier (BBB), and neuronal death contribute to the mortality and morbidity associated with WNV-induced meningitis. Compromised BBB indicates the ability of the virus to gain entry into the CNS via the BBB, however, the underlying mechanisms, and the specific cell types associated with WNV-CNS trafficking are not well understood. Brain microvascular endothelial cells, the main component of the BBB, represent a barrier to virus dissemination into the CNS and could play key role in WNV spread via hematogenous route. To investigate WNV entry into the CNS, we infected primary human brain microvascular endothelial (HBMVE) cells with the neurovirulent strain of WNV (NY99) and examined WNV replication kinetics together with the changes in the expressions of key tight junction proteins (TJP) and cell adhesion molecules (CAM). WNV infection of HBMVE cells was productive as analyzed by plaque assay and qRT-PCR, and did not induce cytopathic effect. Increased mRNA and protein expressions of TJP (claudin-1) and CAM (vascular cell adhesion molecule and E-selectin) were observed at days 2 and 3 after infection, respectively, which coincided with the peak in WNV replication. Further, using an in vitro BBB model comprised of HBMVE cells, we demonstrate that cell-free WNV can cross the BBB, without compromising the BBB integrity. These data suggest that infection of HBMVE cells can facilitate entry of cell-free virus into the CNS without disturbing the BBB, and increased CAM may assist in the trafficking of WNV-infected immune cells into the CNS, via 'Trojan horse' mechanism, thereby contributing to WNV dissemination in the CNS and associated pathology.

  15. All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner.

    Science.gov (United States)

    Kavran, Jennifer M; Ward, Matthew D; Oladosu, Oyindamola O; Mulepati, Sabin; Leahy, Daniel J

    2010-08-06

    Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals. Distribution, movement, and reception of Hh signals are tightly regulated, and abnormal Hh signaling is associated with developmental defects and cancer. In addition to the integral membrane proteins Patched and Smoothened, members of the Drosophila Ihog family of adhesion-like molecules have recently been shown to bind Hh proteins with micromolar affinity and positively regulate Hh signaling. Cell adhesion molecule-related, down-regulated by oncogenes (CDO) and Brother of CDO (BOC) are the closest mammalian relatives of Drosophila Ihog, and CDO binds Sonic Hh with micromolar affinity and positively regulates Hh signaling. Despite these similarities, structural and biochemical studies have shown that Ihog and CDO utilize nonorthologous domains and completely different binding modes to interact with cognate Hh proteins. We report here biochemical and x-ray structural studies of Sonic, Indian, and Desert Hh proteins both alone and complexed with active domains of CDO and BOC. These results show that all mammalian Hh proteins bind CDO and BOC in the same manner. We also show that interactions between Hh proteins and CDO are weakened at low pH. Formation of Hh-mediated Hh oligomers is thought to be an important feature of normal Hh signaling, but no conserved self-interaction between Hh proteins is apparent from inspection of 14 independent Hh-containing crystal lattices.

  16. Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients

    Directory of Open Access Journals (Sweden)

    Karina Karis

    2018-01-01

    Full Text Available Neural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ. IgLON proteins have been shown to be involved in neurite outgrowth, synaptic plasticity and neuronal connectivity, all of which have been shown to be altered in the brains of patients with the diagnosis of schizophrenia. Here we optimized custom 5′-isoform-specific TaqMan gene-expression analysis for the transcripts of human IgLON genes to study the expression of IgLONs in the dorsolateral prefrontal cortex (DLPFC of schizophrenic patients (n = 36 and control subjects (n = 36. Uniform 5′-region and a single promoter was confirmed for the human NEGR1 gene by in silico analysis. IgLON5, a recently described family member, was also included in the study. We detected significantly elevated levels of the NEGR1 transcript (1.33-fold increase and the NTM 1b isoform transcript (1.47-fold increase in the DLPFC of schizophrenia patients compared to healthy controls. Consequent protein analysis performed in male subjects confirmed the increase in NEGR1 protein content both in patients with the paranoid subtype and in patients with other subtypes. In-group analysis of patients revealed that lower expression of certain IgLON transcripts, mostly LSAMP 1a and 1b, could be related with concurrent depressive endophenotype in schizophrenic patients. Additionally, our study cohort provides further evidence that cannabis use may be a relevant risk factor associated with suicidal behaviors in psychotic patients. In conclusion, we provide clinical evidence of increased expression levels of particular IgLON family members in the DLPFC of schizophrenic patients. We propose that alterations in the expression profile of IgLON neural adhesion molecules are associated with brain

  17. Melanophore migration and survival during zebrafish adult pigment stripe development require the immunoglobulin superfamily adhesion molecule Igsf11.

    Directory of Open Access Journals (Sweden)

    Dae Seok Eom

    Full Text Available The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11. We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation.

  18. CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2......) dependent to demonstrate the relative roles of CD54, MHC II, and CD40 signaling in the events leading to the induction of B cell proliferation and responsiveness to IL-2. Paraformaldehyde-fixed activated Th1-induced expression of IL-2R alpha, IL-2R beta, and B7, and upregulated MHC II and CD54 on B cells....... Anti-CD54 and MHC II mAbs as well as a CD8 alpha-CD40 ligand (L) soluble construct inhibited both the T-dependent induction of Ig secretion, and B cell phenotypic changes. We then compared the effects of activated Th1 cells with that of cross-linking these molecules. Cross-linking of CD54 and MHC II...

  19. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Rubina, Kseniya A., E-mail: rkseniya@mail.ru; Surkova, Ekaterina I.; Semina, Ekaterina V.; Sysoeva, Veronika Y.; Kalinina, Natalia I. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation); Poliakov, Alexei A. [Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom); Treshalina, Helena M. [Federal State Budgetary Scietific Institution «N.N. Blokhin Russian Cancer Research Center» (FSBSI “N.N.Blokhin RCRC”), Kashirskoe Shosse 24, Moscow 115478 (Russian Federation); Tkachuk, Vsevolod A. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation)

    2015-07-21

    T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate that T-cadherin overexpression leads to the increase in the expression of anti-angiogenic molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells.

  20. Differentiation of MCF-7 tumor cells from leukocytes and fibroblast cells using epithelial cell adhesion molecule targeted multicore surface-enhanced Raman spectroscopy labels

    Science.gov (United States)

    Freitag, Isabel; Matthäus, Christian; Csaki, Andrea; Clement, Joachim H.; Cialla-May, Dana; Weber, Karina; Krafft, Christoph; Popp, Jürgen

    2015-05-01

    Identification of tumor and normal cells is a promising application of Raman spectroscopy. The throughput of Raman-assisted cell sorting is limited by low sensitivity. Surface-enhanced Raman spectroscopy (SERS) is a well-recognized candidate to increase the intensity of Raman signals of cells. First, different strategies are summarized to detect tumor cells using targeted SERS probes. Then, a protocol is described to prepare multicore-SERS-labels (MSLs) by aggregating gold nanoparticles, coating with a reporter molecule and a thin silver shell to further boost enhancement, encapsulating with a stable silica layer, and functionalizing by epithelial cell adhesion molecule (EpCAM) antibodies. Raman, dark field and fluorescence microscopy proved the specific and nonspecific binding of functionalized and nonfunctionalized MSLs to MCF-7 tumor cells, leukocytes from blood, and nontransformed human foreskin fibroblasts. Raman imaging and dark field microscopy indicated no uptake of MSLs, yet binding to the cellular membrane. Viability tests were performed with living tumor cells to demonstrate the low toxicity of MSL-EpCAM. The SERS signatures were detected from cells with exposure times down to 25 ms at 785-nm laser excitation. The prospects of these MSLs in multiplex assays, for enumeration and sorting of circulating tumor cells in microfluidic chips, are discussed.

  1. Podocalyxin is a novel polysialylated neural adhesion protein with multiple roles in neural development and synapse formation.

    OpenAIRE

    Nathalia Vitureira; Rosa Andrés; Esther Pérez-Martínez; Albert Martínez; Ana Bribián; Juan Blasi; Shierley Chelliah; Guillermo López-Doménech; Fernando De Castro; Ferran Burgaya; Kelly McNagny; Eduardo Soriano

    2010-01-01

    Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that...

  2. Gender and age peculiarities of content changes of protein C, von Willebrand factor, vascular cell adhesion molecules sVCAM-1 in patients with acute left ventricle Q-wave myocardial infarction

    Directory of Open Access Journals (Sweden)

    S. M. Kyselov

    2015-04-01

    Full Text Available Markers of hemostasis have an influence on the state of postinfarction remodeling processes. Aim. In order to study the gender and age peculiarities, to determine the predictive value of the protein C, von Willebrand factor and vascular cell adhesion molecules sVCAM-1 concentration, we examined 76 patients with acute Q-wave myocardial infarction. Methods and results. On the 1st day of the disease, higher concentrations of protein C were detected in young women, vascular cell adhesion molecules sVCAM-1 - in men of any age. On the 10th day of the disease, both in men and women increase in the content of protein C, reducing the concentration of von Willebrand factor and vascular cell adhesion molecules sVCAM-1 were detected. Conclusion. Protein C has the highest prognostic potential in relation to the formation of heart aneurysm after Q-wave myocardial infarction in women of young age, and von Willebrand factor and vascular cell adhesion molecules sVCAM-1 - in older men.

  3. N-methyl-D-aspartate receptor independent changes in expression of polysialic acid-neural cell adhesion molecule despite blockade of homosynaptic long-term potentiation and heterosynaptic long-term depression in the awake freely behaving rat dentate gyrus

    Czech Academy of Sciences Publication Activity Database

    Rodríguez Arellano, Jose Julio; Dallerac, G. M.; Tabuchi, M.; Davies, H.A.; Colyer, F. M.; Stewart, M.G.; Doyere, V.

    2008-01-01

    Roč. 4, 03 (2008), s. 169-178 ISSN 1740-925X Institutional research plan: CEZ:AV0Z50390703 Keywords : Adhesion molecules * hippocampus * synaptic plasticity Subject RIV: FH - Neurology Impact factor: 0.937, year: 2008

  4. Expression of co-stimulatory and adhesion molecules and chemokine or apoptosis receptors on acute myeloid leukaemia : high CD40 and CD11a expression correlates with poor prognosis

    NARCIS (Netherlands)

    Brouwer, RE; Hoefnagel, J; van der Burg, BB; Jedema, [No Value; Zwinderman, KH; Starrenburg, ICW; Kluin-Nelemans, HC; Barge, RMY; Willemze, R; Falkenburg, JHF

    2001-01-01

    The expression of adhesion and co-stimulatory molecules. and chemokine and death receptors such as tumour necrosis factor (TNF) and FAS on acute myeloid leukaemia (AML) may influence the biology of the disease and response to chemotherapy and immunotherapy. In this study, we analysed the expression

  5. Triglyceride-rich lipoprotein modulates endothelial vascular cell adhesion molecule (VCAM-1 expression via differential regulation of endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Ying I Wang

    Full Text Available Circulating triglyceride-rich lipoproteins (TGRL from hypertriglyceridemic subjects exacerbate endothelial inflammation and promote monocyte infiltration into the arterial wall. We have recently reported that TGRL isolated from human blood after a high-fat meal can elicit a pro- or anti-atherogenic state in human aortic endothelial cells (HAEC, defined as up- or down-regulation of VCAM-1 expression in response to tumor necrosis factor alpha (TNFα stimulation, respectively. A direct correlation was found between subjects categorized at higher risk for cardiovascular disease based upon serum triglycerides and postprandial production of TGRL particles that increased VCAM-1-dependent monocyte adhesion to inflamed endothelium. To establish how TGRL metabolism is linked to VCAM-1 regulation, we examined endoplasmic reticulum (ER stress and the unfolded protein response (UPR pathways. Regardless of its atherogenicity, the rate and extent of TGRL internalization and lipid droplet formation by HAEC were uniform. However, pro-atherogenic TGRL exacerbated ER membrane expansion and stress following TNFα stimulation, whereas anti-atherogenic TGRL ameliorated such effects. Inhibition of ER stress with a chemical chaperone 4-phenylbutyric acid decreased TNFα-induced VCAM-1 expression and abrogated TGRL's atherogenic effect. Activation of ER stress sensors PKR-like ER-regulated kinase (PERK and inositol requiring protein 1α (IRE1α, and downstream effectors including eukaryotic initiation factor-2α (eIF2α, spliced X-box-binding protein 1 (sXBP1 and C/EBP homologous protein (CHOP, directly correlated with the atherogenic activity of an individual's TGRL. Modulation of ER stress sensors also correlated with changes in expression of interferon regulatory factor 1 (IRF-1, a transcription factor of Vcam-1 responsible for regulation of its expression. Moreover, knockdown studies using siRNA defined a causal relationship between the PERK/eIF2α/CHOP pathway and

  6. Negative Expression of Melanoma Cell Adhesion Molecule (MCAM Correlated with Axillary Lymph Node Metastasis in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sartika Nurwenda

    2016-09-01

    Full Text Available Triple negative breast cancer (TNBC is breast cancer that demonstrate the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. TNBC has an aggressive behaviour, high frequency of metastasis to the axillary lymph nodes and recurrence, and poor prognosis. Metastasis to the axillary lymph nodes will affect the rate of survival and recurrence in TNBC. Melanoma cell adhession molecule (MCAM is a membrane glycoprotein of the immunoglobulin superfamily, which is involved in the cells binding, which later became known as the marker for the progression and metastasis of melanoma and carcinoma of the prostate. However, MCAM role in mammary carcinoma still controversial. The aim of this study was to assess correlation between MCAM expression with incidence of metastatic to axillary lymph nodes in TNBC. This research was conducted during January 1st 2010–April 31st 2015 at Pathology Anatomy, Faculty of Medicine, Universitas Padjadjaran. This study used a cross-sectional design, using lambda correlation test. MCAM immunohistochemical staining performed on 56 samples of paraffin blocks of TNBC group that did not metastasized and has metastasized to the axillary lymph nodes. A total of 22 of 28 (78.6% of TNBC metastatic to axillary lymph nodes have histoskor MCAM value <4 (negative, whereas 16 of 28 (57.1% of TNBC non-metastatic have histoskor value ≥ 4 (positive. Negative expression of MCAM correlated with TNBC that had metastasized to axillary lymph nodes, although not the only factor that influenced them.

  7. Relative role of upstream regulators of Akt, ERK and CREB in NCAM- and FGF2-mediated signalling

    DEFF Research Database (Denmark)

    Ditlevsen, D.K.; Owczarek, S.; Berezin, V.

    2008-01-01

    with an NCAM ligand, the C3d peptide. NCAM-mediated ERK phosphorylation depended on activation of the fibroblast growth factor receptor (FGFR), Src-family kinases, MEK (MAP and ERK kinase) and G(0)/G(i)-proteins, whereas NCAM-mediated CREB phosphorylation depended on the activity of Src-family kinases and MEK...... for phosphorylation of ERK, Akt, and CREB. MEK was required for phosphorylation of ERK and CREB, but not Akt, whereas G(0)/G(i)-proteins were necessary for phosphorylation of Akt and CREB, and cGMP was necessary for Akt phosphorylation. We thus demonstrate that even though NCAM and FGF2 have many signalling features...

  8. Lutein modulates transcription dysregulation of adhesion molecules and spermatogenesis transcription factors induced by testicular ischemia reperfusion injury: it could be SAFE.

    Science.gov (United States)

    Al-Maghrebi, May; Renno, Waleed M; Al-Somali, Hoda F; Botras, Marina S; Qadhi, Iman N

    2016-05-01

    Testicular ischemia reperfusion injury (tIRI) is considered as the underlying mechanism of testicular torsion, which can cause male infertility. tIRI-induced damage was investigated by assessing the gene expression of spermatogenesis master transcription factors (TFs) and that of major adhesion molecules of the blood-testis barrier. The effect of lutein, a hydroxyl carotenoid, in alleviating tIRI-induced damage was also studied. Male Sprague-Dawley rats were divided into three groups: sham, unilateral tIRI, and tIRI + lutein (0.2 mg/kg). tIRI was induced by occlusion of the testicular artery for 1 h, followed by 4 h of reperfusion. Lutein was injected 15 min after the start of ischemia. Histological analysis and real-time polymerase chain reaction revealed significant decreases in tissue biopsy scores, reduced seminiferous tubule diameters, and downregulated the mRNA expression of the TFs cAMP-responsive element modulator (CREM), TATA box-binding protein-related factor 2 (TRF2), and regulatory factor X 2 (RFX2) compared with the sham group. Lutein treatment reversed these effects. The mRNA expression of the adhesion molecules N-cadherin, nectin-2, claudin-11, occludin, and connexin-43 was significantly downregulated during tIRI, but this change was prevented by lutein treatment. In addition, lutein normalized the tIRI-induced increase in total antioxidant capacity, increased malondialdehyde (MDA) levels, augmented number of TdT-mediated dUTP-X nick-end labeling (TUNEL)-positive nuclei, and activated caspase-8 pathway. The components of survivor activating factor enhancement (SAFE) were also activated during tIRI. Increased tissue expression of TNF-α and its receptor, TNFR1, was accompanied by increased phosphorylation of Janus kinase (JAK) and STAT3, which was prevented by lutein treatment. Our findings suggested that tIRI-induced spermatogenic damage may involve modulation of the SAFE pathway and could benefit from lutein treatment.

  9. Common Phenolic Metabolites of Flavonoids, but Not Their Unmetabolized Precursors, Reduce the Secretion of Vascular Cellular Adhesion Molecules by Human Endothelial Cells.

    Science.gov (United States)

    Warner, Emily F; Zhang, Qingzhi; Raheem, K Saki; O'Hagan, David; O'Connell, Maria A; Kay, Colin D

    2016-03-01

    Flavonoids have been implicated in the prevention of cardiovascular disease; however, their mechanisms of action have yet to be elucidated, possibly because most previous in vitro studies have used supraphysiological concentrations of unmetabolized flavonoids, overlooking their more bioavailable phenolic metabolites. We aimed to explore the effects of phenolic metabolites and their precursor flavonoids at physiologically achievable concentrations, in isolation and combination, on soluble vascular cellular adhesion molecule-1 (sVCAM-1). Fourteen phenolic acid metabolites and 6 flavonoids were screened at 1 μM for their relative effects on sVCAM-1 secretion by human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha (TNF-α). The active metabolites were further studied for their response at different concentrations (0.01 μM-100 μM), structure-activity relationships, and effect on vascular cellular adhesion molecule (VCAM)-1 mRNA expression. In addition, the additive activity of the metabolites and flavonoids was investigated by screening 25 unique mixtures at cumulative equimolar concentrations of 1 μM. Of the 20 compounds screened at 1 μM, inhibition of sVCAM-1 secretion was elicited by 4 phenolic metabolites, of which protocatechuic acid (PCA) was the most active (-17.2%, P = 0.05). Investigations into their responses at different concentrations showed that PCA significantly reduced sVCAM-1 15.2-36.5% between 1 and 100 μM, protocatechuic acid-3-sulfate and isovanillic acid reduced sVCAM-1 levels 12.2-54.7% between 10 and 100 μM, and protocatechuic acid-4-sulfate and isovanillic acid-3-glucuronide reduced sVCAM-1 secretion 27.6% and 42.8%, respectively, only at 100 μM. PCA demonstrated the strongest protein response and was therefore explored for its effect on VCAM-1 mRNA, where 78.4% inhibition was observed only after treatment with 100 μM PCA. Mixtures of the metabolites showed no activity toward sVCAM-1, suggesting no additive

  10. Combined treatment with amlodipine and atorvastatin calcium reduces circulating levels of intercellular adhesion molecule-1 and tumor necrosis factor-α in hypertensive patients with prediabetes

    Directory of Open Access Journals (Sweden)

    Zhouqing Huang

    2016-08-01

    Full Text Available Amlodipine and atorvastatin combination reduces levels of ICAM-1 and TNF-α in hypertensive prediabetesAbstractObjective: To assess the effect of amlodipine and atorvastatin on intercellular adhesion molecule (ICAM-1 and tumor necrosis factor (TNF-α expression, as endothelial function and inflammation indicators, respectively, in hypertensive patients with and without prediabetes.Methods: Forty-five consecutive patients with hypertension, diagnosed according to JNC7, were divided into two groups based on the presence (HD group, n=23 or absence (H group, n=22 of prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose tolerance and fasting glucose. All patients simultaneously underwent 12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium combination (5/10mg; Hisun-Pfizer Pharmaceuticals Co. Ltd. Serum isolated before and after treatment from overnight fasting blood samples was analyzed by ELISA.Results: In the HD and H groups after vs. before 12-week amlodipine/atorvastatin treatment, there were significantly (all P <.01 lower levels of ICAM-1 (3.06 ± 0.34 vs. 4.07 ± 0.70 pg/ml; 3.26 ± 0.32 vs. 3.81 ± 0.60 pg/ml, respectively and TNF-α (78.71 ± 9.19 vs. 110.94 ± 10.71 pg/ml; 80.95 ± 9.33 vs. 101.79 ±11.72 pg/ml, respectively, with more pronounced reductions in HD vs. H group (ICAM-1Δ: 1.01 ± 0.80 vs. 0.55 ± 0.64 pg/ml, respectively, P = 0.037; TNF-αΔ: 32.23 ± 14.33 vs. 20.84 ± 14.89 pg/ml, respectively, P= 0.011, independently from blood pressure and cholesterol level reduction.Conclusions: Amlodipine/atorvastatin improved endothelial function and inflammation, as reflected by lower circulating levels of ICAM-1 and TNF-α, more prominently in hypertensives with than without prediabetes. Starting statin treatment before overt diabetes in hypertensives thus might improve cardiovascular outcomes.Keywords: Amlodipine and atorvastatin calcium; prediabetes; hypertension

  11. Clinical and experimental studies regarding the expression and diagnostic value of carcinoembryonic antigen-related cell adhesion molecule 1 in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Zhou, Mu-qing; Du, Yan; Liu, Yi-wen; Wang, Ying-zhi; He, Yi-qing; Yang, Cui-xia; Wang, Wen-juan; Gao, Feng

    2013-01-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in non-small-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC. The expression of the serum CEACAM1 was determined by enzyme-linked immunosorbent assay. The protein expression and the location of CEACAM1 in tumours were observed by immunohistochemical staining. The CEACAM1 mRNA levels in tumour and normal adjacent tissues were measured using quantitative real-time PCR, and the expression patterns and the rate of CEACAM1-S and CEACAM1-L were analysed by reverse transcription-PCR. Serum CEACAM1 levels were significantly higher in NSCLC patients compared with that from normal healthy controls (P <0.0001). 17 patients (81%) among 21 showed high expression of CEACAM1 by immunohistochemical staining. Although no significant differences were found between tumour and normal tissues on mRNA expression levels of CEACAM1 (P >0.05), the CEACAM1-S and the CEACAM1-S/L (S: L) ratios were significantly higher in tumour than normal tissues (P <0.05). Our data indicated that the serum levels of CEACAM1 could discriminate lung cancer patients from health donors and that CEACAM1 might be a useful marker in early diagnosis of NSCLC. Moreover, our results showed that the expression patterns of CEACAM1 isoforms could be changed during oncogenesis, even when total CEACAM1 in tumour tissues did not show significant changes. Our study suggested that the expression ratios of CEACAM1-S/CEACAM1-L might be a better diagnostic indicator in NSCLC than the quantitative

  12. Moléculas de adhesión: su papel en la fisiopatologIa cardiovascular Adhesion molecules: Their role in cardiovascular physiopathology

    Directory of Open Access Journals (Sweden)

    Ariel Jaitovich

    2004-10-01

    Full Text Available Las moléculas de adhesión son receptores de membrana que participan en diversas funciones vinculadas al tráfico celular, a las interacciones célula-célula y célula-matriz extracelular. Tres grupos de estas moléculas, conocidas como"adhesinas", están relacionados con la enfermedad cardiovascular: integrinas, selectinas y superfamilia de inmunoglobulinas. Intervienen en los fenómenos de activación y disfunción endotelial y se vinculan a la patogenia de la enfermedad coronaria, la injuria por reperfusión, el rechazo del corazón transplantado, la miocarditis, la miocardiopatía hipertrófica, etc. Se asocian también con el mecanismo de acción de las estatinas. El dosaje de los niveles séricos de las moléculas de adhesión tiene valor diagnóstico y predictivo de diversas enfermedades cardiovasculares. Esta revisión enfoca las variadas funciones de las adhesinas y se orienta sobre diversas posibilidades terapéuticas derivadas de su conocimiento.Adhesion molecules are membrane receptors that mediate several functions related to cell traffic, cell-cell interactions, and cell-matrix contact. There are three important groups associated to cardiovascular disease: integrins, selectins, and the immunoglobulin superfamily. They are involved in the endothelial disfunction and activation processes, and are related to the pathogenesis of coronary artery disease, reperfusion injury, allograft vasculopathy, myocarditis, hypertrophic myocardiopathy, etc. Also, they are related to the mechanism of action of statins. Serologic titer of these molecules has diagnostic and predictive value on diverse cardiovascular diseases. This review focuses on the functions of adhesins and discusses various therapeutic possibilities based on their recognition.

  13. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2011-05-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  14. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2012-02-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  15. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Hao Hong

    Full Text Available New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM were then genetically modified to express an anti-L1-CAM CAR (CE7R, which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p. administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

  16. Epithelial cell adhesion molecule is expressed in a subset of sarcomas and correlates to the degree of cytological atypia in leiomyosarcomas

    Science.gov (United States)

    WARD, KRISTI; AMAYA, CLARISSA; VERMA, KUNDAN; TRAN, DAT; DIAZ, DOLORES; TORABI, ALIREZA; BRYAN, BRAD A.

    2015-01-01

    Epithelial cell adhesion molecule (EpCAM) is a protein involved in cell-to-cell attachment and is considered to be strictly expressed in epithelial tissues and epithelial-derived tumors. Furthermore, EpCAM has been shown to be a negative prognostic marker for several carcinomas. In this study, we performed a genomic meta-analysis of gene expression profiles housed in the Cancer Cell Line Encyclopedia to demonstrate that EpCAM mRNA is expressed at low to moderate levels in certain sarcoma cell lines. We utilized immunohistochemical staining to confirm that the EpCAM protein is expressed in a subset of angiosarcomas and leiomyosarcomas and in all the investigated osteosarcomas. Finally, we conducted a statistical analysis of clinical data to demonstrate that EpCAM protein expression is significantly and directly correlated with the degree of cytological atypia in leiomyosarcomas. In conclusion, this data suggests that, contrary to conventional beliefs, EpCAM is expressed in a subset of sarcomas and is a negative prognostic marker for leiomyosarcomas. PMID:25469266

  17. [Human soluble dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin inhibits phagocytosis of Staphylococcus aureus by immature dendritic cells].

    Science.gov (United States)

    Li, Hui-Jie; Xu, Tian-Yu; Zhou, Jia; Zhu, Ling-Yan; Zhang, Li-Yun; Lu, Xiao; Chen, Zheng-Liang

    2015-04-01

    To study the effect and mechanism of soluble dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (sDC-SIGN) on the phagocytosis of Staphylococcus aureus (S. aureus) by immature dendritic cells (imDCs). Flow cytometry was employed to examine the effect of sDC-SIGN on the phagocytosis of S. aureus by imDCs. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the binging of sDC-SIGN to S. aureus, lipoteichoic acid (LTA) and lipopolysaccharides (LPS) and investigate the effect of the ligands mannan and LTA and anti-DC-SIGN antibodies 1C6 and 4H3 on the binging of sDC-SIGN to S. aureus. sDC-SIGN inhibited the phagocytosis of S. aureus by imDCs. sDC-SIGN bound to S. aureus in a Ca(2+)-dependent manner. sDC-SIGN concentration-dependently bound to LTA, but not to LTA, and the binging of sDC-SIGN to S. aureus was blocked by mannan, LTA, 1C6 and 4H3. sDC-SIGN preferentially binds to the carbohydrate constituents on S. aureus to affect the binding between membrane-bound DC-SIGN and S. aureus, thus suppressing the phagocytosis of S. aureus by imDCs.

  18. Epigenetic Silencing of a Proapoptotic Cell Adhesion Molecule, the Immunoglobulin Superfamily Member IGSF4, by Promoter CpG Methylation Protects Hodgkin Lymphoma Cells from Apoptosis

    Science.gov (United States)

    Murray, Paul G.; Fan, Yichao; Davies, Gillian; Ying, Jianming; Geng, Hua; Ng, Ka Man; Li, Hongyu; Gao, Zifen; Wei, Wenbin; Bose, Shikha; Anderton, Jennifer; Kapatai, Georgia; Reynolds, Gary; Ito, Akihiko; Marafioti, Teresa; Woodman, Ciaran BJ; Ambinder, Richard; Tao, Qian

    2010-01-01

    The malignant Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) are believed to derive from germinal center (GC) B cells, but lack expression of a functional B cell receptor. As apoptosis is the normal fate of B-cell receptor–negative GC B cells, mechanisms that abrogate apoptosis are thus critical in HL development, such as epigenetic disruption of certain pro-apoptotic cancer genes including tumor suppressor genes. Identifying methylated genes elucidates oncogenic mechanisms and provides valuable biomarkers; therefore, we performed a chemical epigenetic screening for methylated genes in HL through pharmacological demethylation and expression profiling. IGSF4/CADM1/TSLC1, a pro-apoptotic cell adhesion molecule of the immunoglobulin superfamily, was identified together with other methylated targets. In contrast to its expression in normal GC B cells, IGSF4 was down-regulated and methylated in HL cell lines, most primary HL, and microdissected HRS cells of 3/5 cases, but not in normal peripheral blood mononuclear cells and seldom in normal lymph nodes. We also detected IGSF4 methylation in sera of 14/18 (78%) HL patients but seldom in normal sera. Ectopic IGSF4 expression decreased HL cells survival and increased their sensitivity to apoptosis. IGSF4 induction that normally follows heat shock stress treatment was also abrogated in methylated lymphoma cells. Thus, our data demonstrate that IGSF4 silencing by CpG methylation provides an anti-apoptotic signal to HRS cells important in HL pathogenesis. PMID:20709797

  19. Prognostic Significance of Activated Leukocyte Cell Adhesion Molecule (ALCAM in Association with Promoter Methylation of the ALCAM Gene in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Young Ju Jeong

    2018-01-01

    Full Text Available Activated leukocyte cell adhesion molecule (ALCAM has been implicated in tumorigenesis. In this study, we studied DNA methylation status of the ALCAM gene using pyrosequencing in breast cancer tissues. We analyzed the association between the methylation status of the ALCAM gene and its expression. Also, the effects of inflammation on the ALCAM gene methylation and its expression were investigated. The ALCAM gene methylation was associated with the ALCAM transcripts in tumor tissues. The methylation status of the ALCAM gene was not significantly different between tumor and normal tissues. The level of ALCAM transcripts was associated with the expression of TNFα, NF-κB p50, IL-4, and intratumoral inflammation. The IHC expression of ALCAM was associated with histologic grade, HER2 overexpression and molecular subtype. The expression of TNFα, NF-κB p50, and IL-4 showed significant association with the clinicopathologic characteristics. In conclusion, the ALCAM gene methylation was related to the level of ALCAM transcripts. Also, the level of ALCAM transcripts was associated with the inflammatory markers in breast cancer. Our results suggest that the methylation of the ALCAM gene contributes to the decreased expression of ALCAM. Also, ALCAM is linked to the inflammatory response in breast cancer.

  20. Cocaine-associated retiform purpura: a C5b-9-mediated microangiopathy syndrome associated with enhanced apoptosis and high levels of intercellular adhesion molecule-1 expression.

    Science.gov (United States)

    Magro, Cynthia M; Wang, Xuan

    2013-10-01

    Cocaine-associated retiform purpura is a recently described entity characterized by striking hemorrhagic necrosis involving areas of skin associated with administration of cocaine. Levamisole, an adulterant in cocaine, has been suggested as the main culprit pathogenetically. Four cases of cocaine-associated retiform purpura were encountered in the dermatopathology practice of C. M. Magro. The light microscopic findings were correlated with immunohistochemical and immunofluorescence studies. All 4 cases showed a very striking thrombotic diathesis associated with intravascular macrophage accumulation. Necrotizing vasculitis was noted in 1 case. Striking intercellular adhesion molecule-1 (ICAM-1)/CD54 expression in vessel wall along with endothelial expression of caspase 3 and extensive vascular C5b-9 deposition was observed in all biopsies examined. Cocaine-induced retiform purpura is a C5b-9-mediated microvascular injury associated with enhanced apoptosis and prominent vascular expression of ICAM-1, all of which have been shown in prior in vitro and in vivo murine models to be a direct effect of cocaine metabolic products. Antineutrophilic cytoplasmic antibody and antiphospholipid antibodies are likely the direct sequelae of the proapoptotic microenvironment. The inflammatory vasculitic lesion could reflect the downstream end point reflective of enhanced ICAM-1 expression and the development of antineutrophilic cytoplasmic antibody. Levamisole likely works synergistically with cocaine in the propagation of this syndromic complex.

  1. Extracellular matrix proteins and carcinoembryonic antigen-related cell adhesion molecules characterize pancreatic duct fluid exosomes in patients with pancreatic cancer.

    Science.gov (United States)

    Zheng, Jian; Hernandez, Jonathan M; Doussot, Alexandre; Bojmar, Linda; Zambirinis, Constantinos P; Costa-Silva, Bruno; van Beek, Elke J A H; Mark, Milica T; Molina, Henrik; Askan, Gokce; Basturk, Olca; Gonen, Mithat; Kingham, T Peter; Allen, Peter J; D'Angelica, Michael I; DeMatteo, Ronald P; Lyden, David; Jarnagin, William R

    2018-01-12

    Exosomes are nanovesicles that have been shown to mediate carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Given the direct communication of pancreatic duct fluid with the tumor and its relative accessibility, we aimed to determine the feasibility of isolating and characterizing exosomes from pancreatic duct fluid. Pancreatic duct fluid was collected from 26 patients with PDAC (n = 13), intraductal papillary mucinous neoplasm (IPMN) (n = 8) and other benign pancreatic diseases (n = 5) at resection. Exosomes were isolated by serial ultracentrifugation, proteins were identified by mass spectrometry, and their expression was evaluated by immunohistochemistry. Exosomes were isolated from all specimens with a mean concentration of 5.9 ± 1 × 10 8  particles/mL and most frequent size of 138 ± 9 nm. Among the top 35 proteins that were significantly associated with PDAC, multiple carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and extracellular matrix (ECM) proteins were identified. Interestingly, CEACAM 1/5 expression by immunohistochemistry was seen only on tumor epithelia whereas tenascin C positivity was restricted to stroma, suggesting that both tumor and stromal cells contributed to exosomes. This is the first study showing that exosome isolation is feasible from pancreatic duct fluid, and that exosomal proteins may be utilized to diagnose patients with PDAC. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  2. Activation of transcription factor AP-2 mediates UVA radiation- and singlet oxygen-induced expression of the human intercellular adhesion molecule 1 gene

    International Nuclear Information System (INIS)

    Grether-Beck, S.; Olaizola-Horn, S.; Schmitt, H.; Grewe, M.

    1996-01-01

    UVA radiation is the major component of the UV solar spectrum that reaches the earth, and the therapeutic application of UVA radiation is increasing in medicine. Analysis of the cellular effects of UVA radiation has revealed that exposure of human cells to UVA radiation at physiological doses leads to increased gene expression and that this UVA response is primarily mediated through the generation of singlet oxygen. In this study, the mechanisms by which UVA radiation induces transcriptional activation of the human intercellular adhesion molecule 1 (ICAM-1) were examined. UVA radiation was capable of inducing activation of the human ICAM-1 promoter and increasing OCAM-1 mRNA and protein expression. These UVA radiation effects were inhibited by singlet oxygen quenchers, augmented by enhancement of singlet oxygen life-time, and mimicked in unirradiated cells by a singlet oxygen-generating system. UVA radiation as well as singlet oxygen-induced ICAM-1 promoter activation required activation of the transcription factor AP-2. Accordingly, both stimuli activated AP-2, and deletion of the putative AP-2-binding site abrogated ICAM-1 promoter activation in this system. This study identified the AP-2 site as the UVA radiation- and singlet oxygen-responsive element of the human ICAM-1 gene. The capacity of UVA radiation and/or singlet oxygen to induce human gene expression through activation of AP-2 indicates a previously unrecognized role of this transcription factor in the mammalian stress response. 38 refs., 3 figs., 3 tabs

  3. Leukocytes-depleting filters preferentially remove activated leukocytes and reduce the expression of surface adhesion molecules during the simulated extracorporeal circulation of human blood.

    Science.gov (United States)

    Alexiou, Christos; Sheppard, Stuart; Tang, Augustine; Rengarajan, Arvind; Smith, David; Haw, Marcus; Gibbs, Roz

    2006-01-01

    The effect of leukocyte-depleting filters on the total and activated leukocyte counts and the expression of surface adhesion molecules CD11b, CD18, and CD62L during the in vitro extracorporeal circulation of human blood was studied. A 200 ml blood sample was taken from 10 patients undergoing CABG surgery. The blood was circulated for 60 minutes within an experimental extracorporeal circuit. A leukocyte-depleting filter was attached in five circuits (filtered group). In five other circuits, no filter was used (controls). Total leukocyte counts were determined manually. Activated leukocytes were identified using nitroblue tetrazolium staining. The expression of CD11b, CD18, and CD62L was measured with flow cytometry. At 60 minutes, total leukocyte counts were reduced by 49% from the baseline values in the filtered group and 10% in the control group (p filtered group and increased by 116% in the control group (p filtered group, the expression of CD11b, CD18, and CD612L decreased by 60%, 21%, and 79%, respectively, and in the control group it increased by 24%, 6%, and 28% (p filters preferentially remove activated leukocytes and reduce the expression of CD11b, CD18, and CD62L during the in vitro extracorporeal circulation of human blood.

  4. Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

    Science.gov (United States)

    Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J H; Newman, Debra K; Newman, Peter J; Santoso, Sentot

    2010-04-01

    The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner.

  5. Sphingosine 1-Phosphate Induces Platelet/Endothelial Cell Adhesion Molecule-1 Tyrosine Phosphorylation in Bovine Aortic Endothelial Cells through a PP2-Inhibitable Mechanism

    Directory of Open Access Journals (Sweden)

    Yu-Ting Huang

    2007-12-01

    Full Text Available Sphingosine-1-phosphate (S1P is a low-molecular-weight phospholipid derivative released by activated platelets. S1P transduces signals through a family of G protein-coupled receptors to modulate various physiological behaviors of endothelial cells. Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31 is a 130-kDa protein expressed on the surfaces of leukocytes, platelets, and endothelial cells. Upon PECAM-1 activation, its cytoplasmic tyrosine residues become phosphorylated and bind with SH2 domain-containing proteins, thus leading to the downstream functions mediated by PECAM-1. In the present study, we found that S1P induced PECAM-1 tyrosine phosphorylation and SHP-2 association in bovine aortic endothelial cells (BAECs by immunoprecipitation and western blotting. The pretreatment of BAECs with a series of chemical inhibitors to determine the signaling pathway showed that the PECAM-1 phosphorylation was inhibited by PP2, indicating the participation of Src family kinases. These results demonstrated that S1P induced PECAM-1 tyrosine phosphorylation in BAECs through mediation of Src family kinases, and this may regulate the physiological behaviors of endothelial cells.

  6. Contrasting effects of an ultraviolet B and an ultraviolet A tanning lamp on interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1 expression.

    Science.gov (United States)

    Clingen, P H; Berneburg, M; Petit-Frère, C; Woollons, A; Lowe, J E; Arlett, C F; Green, M H

    2001-07-01

    Recent studies have demonstrated that a tanning lamp emitting predominantly ultraviolet (UV) A induces significant yields of the type of potentially mutagenic DNA damage that are associated with the onset of skin cancer (i.e. cyclobutane pyrimidine dimers). UV-induced immunosuppression is also an important event leading to skin cancer. To the modulation of key immunological molecules following exposure to a broad-spectrum UVB lamp and a predominantly UVA-emitting tanning lamp using model in vitro systems. We compared secretion and mRNA expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in normal human epidermal keratinocytes, and interferon (IFN)-gamma-induced intracellular adhesion molecule (ICAM)-1 in normal human fibroblasts irradiated in vitro with a broad-spectrum UVB lamp or with a Philips 'Performance' tanning lamp. With broad-spectrum UVB irradiation, upregulation of IL-6 and TNF-alpha mRNA was detected 6 h after irradiation, and a dose-dependent increase of cytokines in the supernatants of irradiated cells was found 24 h after irradiation. In contrast, there was no cytokine secretion and little evidence for mRNA upregulation following exposure to a tanning lamp. When cells were exposed first to broad-spectrum UVB, then the tanning lamp, UVB-induced cytokine secretion was inhibited, although mRNA levels were upregulated to a level close to that observed with UVB alone. By using a Schott WG 320 nm filter to attenuate the level of UVB relative to UVA emitted by the tanning lamp, the inhibition of cytokine secretion was shown to be associated with UVA exposure. Both UV sources inhibited IFN-gamma-induced ICAM-1 mRNA expression in a dose-dependent fashion. By using a Schott WG 335 nm filter, inhibition of ICAM-1 mRNA expression by the tanning lamp was shown to be associated with UVB exposure. These results suggest that UV sources emitting different levels of UVA and UVB have differential effects on the modulation of different

  7. [Changes in the serum concentrations of adhesion molecules and vascular endothelial growth factor in active ankylosing spondylitis patients taking amtolmetin guacil: Results of a 56-week prospective ореn-label controlled observational study].

    Science.gov (United States)

    Gaydukova, I Z; Khondkaryan, E V; Aparkina, A V; Rebrov, A P

    To estimate changes in the concentrations of adhesion molecules and vascular endothelial growth factor A after 30-day additional use of amtolmetin guacil (AMG) in patients with active ankylosing spondylitis (AS) who were unresponsive to previous one-year treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). 20 patients with active AS who had not reached a BASDAI score molecules (sICAM-1 and sVCAM-1) and VEGF-A were measured. BASDAI and ASDAS scores and C-reactive protein (CRP) levels were determined in AS patients. The concentrations of adhesion molecules and VEGF-A were investigated in patients with AS at baseline, at 52 weeks after NSAID treatment start, and at 30 days following AMH initiation (at week 56) and in healthy individuals at baseline and at 30 days. The concentration of sICAM-1 in patients with AS was 987.0±217.39, 938.98±293.31, and 364.25±363.3 ng/ml at weeks 0, 52, and 56, respectively; that in healthy individuals was 769.25±189.32 and 740.05±225.76 ng/ml at baseline and at 30 days, respectively. The differences from the baseline concentration were significant in patients with AS (pmolecules and the level of CRP (pmolecules have been found in AS patients compared with healthy individuals. The study has demonstrated that AMG treatment is efficient in treating patients with AS. NSAID/AMG treatment is associated with lower concentrations of adhesion molecules. Decreased CRP levels serve as predictors for reduced concentration of adhesion molecules. The level of VEGF-A at baseline did not differ from that in healthy subjects, but was decreased during treatment with NSAIDs.

  8. Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA.

    Science.gov (United States)

    Lee, Ji-Won; Chen, Hui; Pullikotil, Philomena; Quon, Michael J

    2011-02-25

    FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). Therefore, we hypothesized that FoxO1 is a novel direct substrate for PKA-α. Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). Phosphorylation of wild-type FoxO1 (but not FoxO1-AAA) was detectable using phospho-specific antibodies. Similar results were obtained using purified GST-FoxO1 protein as the substrate. Thus, FoxO1 is a direct substrate for PKA-α in vitro. In bovine aortic endothelial cells, interaction between endogenous PKA-α and endogenous FoxO1 was detected by co-immunoprecipitation. In human aortic endothelial cells (HAEC), pretreatment with H89 (PKA inhibitor) or siRNA knockdown of PKA-α decreased forskolin- or prostaglandin E(2)-stimulated phosphorylation of FoxO1. In HAEC transfected with a FoxO-promoter luciferase reporter, co-expression of the catalytic domain of PKA-α, catalytically inactive mutant PKA-α, or siRNA against PKA-α caused corresponding increases or decreases in transactivation of the FoxO promoter. Expression of vascular cellular adhesion molecule-1 mRNA, up-regulated by FoxO1 in endothelial cells, was enhanced by siRNA knockdown of PKA-α or treatment of HAEC with the PKA inhibitor H89. Adhesion of monocytes to endothelial cells was enhanced by H89 treatment or overexpression of FoxO1-AAA, similar to effects of TNF-α treatment. We conclude that FoxO1 is a novel physiological substrate for PKA-α in vascular endothelial cells.

  9. Interleukin-6 trans-signaling increases the expression of carcinoembryonic antigen-related cell adhesion molecules 5 and 6 in colorectal cancer cells.

    Science.gov (United States)

    Holmer, Reinhild; Wätzig, Georg H; Tiwari, Sanjay; Rose-John, Stefan; Kalthoff, Holger

    2015-12-16

    Colorectal cancer (CRC) is among the five most frequent causes for cancer-related deaths in Europe. One of the most important tumor-associated antigens for CRC is carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), which is involved in cell adhesion, migration, anoikis, tumor invasion and metastasis. Its family member CEACAM6 is also upregulated in adenomas and carcinomas of the colon and an independent predictor of poor survival. Previous studies have reported a link between upregulation of CEACAM5 and interleukin-6 (IL-6). IL-6 plays an important role in CRC progression, and signaling is mediated via two pathways (classic and trans-signaling). However, this link could not be confirmed by other studies, and the role of IL-6 trans-signaling in the CEACAM5 upregulation has not been elucidated. Moreover, the impact of IL-6 on the expression of CEACAM6 has not yet been examined. The expression of IL-6, IL-6 receptor (IL-6R), glycoprotein (gp) 130, CEACAM5 and CEACAM6 was analyzed by RT-PCR, Western blot, flow cytometry or qPCR. Colon cell lines were incubated with IL-6 or Hyper-IL-6 (mediating IL-6 trans-signaling), and subsequently, the expression of CEACAMs was determined by qPCR or Western blot. FLLL31, an inhibitor of the phosphorylation of signal transducer and activator of transcription-3 (STAT3), was used to determine the role of STAT3 phosphorylation. We confirmed that colon carcinoma cell lines express IL-6 and IL-6R. We observed only a weak upregulation of CEACAM5 and CEACAM6 by classic IL-6 signaling, but a strong increase by IL-6 trans-signaling. This upregulation depended on the phosphorylation of STAT3. Our data show the upregulation of the tumor-associated antigens CEACAM5/6 by trans-signaling of the pro-inflammatory cytokine IL-6. This mechanism may contribute to the tumor-promoting role of IL-6 and could therefore be a target for therapeutic intervention in particular by specific inhibitors such as sgp130Fc.

  10. Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate.

    Science.gov (United States)

    Prasad, Ananda S; Beck, Frances W J; Bao, Bin; Snell, Diane; Fitzgerald, James T

    2008-03-15

    Zinc lozenges have been used for treatment of the common cold; however, the results remain controversial. Fifty ambulatory volunteers were recruited within 24 h of developing symptoms of the common cold for a randomized, double-blind, placebo-controlled trial of zinc. Participants took 1 lozenge containing 13.3 mg of zinc (as zinc acetate) or placebo every 2-3 h while awake. The subjective scores for common cold symptoms were recorded daily. Plasma zinc, soluble interleukin (IL)-1 receptor antagonist (sIL-1ra), soluble tumor necrosis factor receptor 1, soluble vascular endothelial cell adhesion molecule, and soluble intercellular adhesion molecule (sICAM)-1 were assayed on days 1 and 5. Compared with the placebo group, the zinc group had a shorter mean overall duration of cold (4.0 vs. 7.1 days; P cold symptoms. We related the improvement in cold symptoms to the antioxidant and anti-inflammatory properties of zinc.

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

    DEFF Research Database (Denmark)

    Hübschmann, Martin; Skladchikova, Galina

    2008-01-01

    Extracellular ATP is an abundant signaling molecule that has a number of functions in the nervous system. It is released by both neurons and glial cells, activates purinergic receptors and acts as a trophic factor as well as a neurotransmitter. In this review, we summarize the evidence for a dire...

  12. Alteration of the cell adhesion molecule L1 expression in a specific subset of primary afferent neurons contributes to neuropathic pain.

    Science.gov (United States)

    Yamanaka, Hiroki; Obata, Koichi; Kobayashi, Kimiko; Dai, Yi; Fukuoka, Tetsuo; Noguchi, Koichi

    2007-02-01

    The cell adhesion molecule L1 (L1-CAM) plays important functional roles in the developing and adult nervous systems. Here we show that peripheral nerve injury induced dynamic post-transcriptional alteration of L1-CAM in the rat dorsal root ganglia (DRGs) and spinal cord. Sciatic nerve transection (SCNT) changed the expression of L1-CAM protein but not L1-CAM mRNA. In DRGs, SCNT induced accumulation of the L1-CAM into the surface of somata, which resulted in the formation of immunoreactive ring structures in a number of unmyelinated C-fiber neurons. These neurons with L1-CAM-immunoreactive ring structures were heavily colocalized with phosphorylated p38 MAPK. Western blot analysis revealed the increase of full-length L1-CAM and decrease of fragments of L1-CAM after SCNT in DRGs. Following SCNT, L1-CAM-immunoreactive profiles in the dorsal horn showed an increase mainly in pre-synaptic areas of laminae I-II with a delayed onset and colocalized with growth-associated protein 43. In contrast to DRGs, SCNT increased the proteolytic 80-kDa fragment of L1-CAM and decreased full-length L1-CAM in the spinal cord. The intrathecal injection of L1-CAM antibody for the extracellular domain of L1-CAM inhibited activation of p38 MAPK and emergence of ring structures of L1-CAM immunoreactivity in injured DRG neurons. Moreover, inhibition of extracellular L1-CAM binding by intrathecal administration of antibody suppressed the mechanical allodynia and thermal hyperalgesia induced by partial SCNT. Collectively, these data suggest that the modification of L1-CAM in nociceptive pathways might be an important pathomechanism of neuropathic pain.

  13. Trypanosoma cruzi infection: a continuous invader-host cell cross talk with participation of extracellular matrix and adhesion and chemoattractant molecules

    Directory of Open Access Journals (Sweden)

    Marino A.P.M.P.

    2003-01-01

    Full Text Available Several lines of evidence have shown that Trypanosoma cruzi interacts with host extracellular matrix (ECM components producing breakdown products that play an important role in parasite mobilization and infectivity. Parasite-released antigens also modulate ECM expression that could participate in cell-cell and/or cell-parasite interactions. Increased expression of ECM components has been described in the cardiac tissue of chronic chagasic patients and diverse target tissues including heart, thymus, central nervous system and skeletal muscle of experimentally T. cruzi-infected mice. ECM components may adsorb parasite antigens and cytokines that could contribute to the establishment and perpetuation of inflammation. Furthermore, T. cruzi-infected mammalian cells produce cytokines and chemokines that not only participate in the control of parasitism but also contribute to the establishment of chronic inflammatory lesions in several target tissues and most frequently lead to severe myocarditis. T. cruzi-driven cytokines and chemokines may also modulate VCAM-1 and ICAM-1 adhesion molecules on endothelial cells of target tissues and play a key role in cell recruitment, especially of activated VLA-4+LFA-1+CD8+ T lymphocytes, resulting in a predominance of this cell population in the inflamed heart, central nervous system and skeletal muscle. The VLA-4+-invading cells are surrounded by a fine network of fibronectin that could contribute to cell anchorage, activation and effector functions. Since persistent "danger signals" triggered by the parasite and its antigens are required for the establishment of inflammation and ECM alterations, therapeutic interventions that control parasitism and selectively modulate cell migration improve ECM abnormalities, paving the way for the development of new therapeutic strategies improving the prognosis of T. cruzi-infected individuals.

  14. Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

    Science.gov (United States)

    Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

    2008-07-01

    Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia. 2008 Wiley-Liss, Inc.

  15. [Detection and clinical value of epithelial cellular adhesion molecule (EpCAM) mRNA positive circulating tumor cells in metastatic breast cancer].

    Science.gov (United States)

    Yan, Ying; Cheng, Jian-ping; Di, Li-jun; Song, Guo-hong; Ren, Jun

    2012-04-18

    To test for circulating tumor cells (CTCs) relying on epithelial cellular adhesion molecule (EpCAM) expression in metastatic breast cancer by quantitative real-time reverse transcription-PCR. In the study,47 metastatic breast cancer patients were evaluated by quantitative real-time PCR for detecting EpCAM mRNA. In addition, analyses were carried out for their correlation with patients' clinicopathologic features, response, and the time to progression (TTP). The sensitivity of EpCAM mRNA in the metastatic breast cancer patients was about 40%. However, the specificity of EpCAM mRNA for 20 healthy controls was 100%. TTP was calculated, and compared with that between EpCAM mRNA-positive and EpCAM mRNA-negative groups. For the retrospective study, the median TTP was 7.1 months and 11.1 months (P=0.013) for patients with EpCAM mRNA-positive and EpCAM mRNA-negative, respectively, after the first cycle chemotherapy. Moreover, a statistically significant correlation was demonstrated between EpCAM mRNA and TTP in patients who underwent the first or the second-line chemotherapy (P=0.018), but there was no significance in the patients pretreated with two or more previous chemotherapy lines (P=0.471). This study provides evidence of the presence of EpCAM mRNA in approximately 40% of patients with metastatic breast cancer. There is a strong correlation between EpCAM mRNA results after the first cycle therapy and TTP in metastatic breast cancer patients, and EpCAM mRNA positive after chemotherapy may predict shorter TTP.

  16. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

    LENUS (Irish Health Repository)

    Harmon, D

    2012-02-03

    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol\\/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg\\/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

  17. Effects of aqueous extracts of Taraxacum Officinale on expression of tumor necrosis factor-alpha and intracellular adhesion molecule 1 in LPS-stimulated RMMVECs.

    Science.gov (United States)

    Hu, Ge; Wang, Junjie; Hong, Dong; Zhang, Tao; Duan, Huiqin; Mu, Xiang; Yang, Zuojun

    2017-01-11

    Mastitis gives rise to big financial burden to farm industry (mainly dairy production) and public health. Its incidence is currently high and therefore, highly effective treatments for therapy, especially with natural products are required. Taraxacum officinale has been reported to use for anti-inflammation. However, its effect on endothelium during mastitis has not been reported. We firstly established inflammation experimental model of rat mammary microvascular endothelial cells (RMMVECs). We evaluated the effects of dandelion leaf aqueous extracts (DAE) on LPS-induced production of inflammatory mediators in RMMVECs by enzyme-linked immunosorbent assay and Western blot. We treated RMMVECs with 1 μg/ml LPS for 4 h and then incubated with 10, 100 and 200 μg/mL DAE for 4, 8, 12 and 24 h. The expression (mRNA and protein level) of targets (tumor necrosis factor-alpha (TNF- α) and Intracellular Adhesion Molecule 1 (ICAM1) was analyzed by employing real-time PCR and Western blots. The in vivo anti-inflammatory effect of DAE on mastitis within an Staphylococcus aureus-induced mouse model was also determined. The obtained results showed that dandelion extracts at the concentration of 100 and 200 μg/mL could significantly inhibit both TNF-α and ICAM-1 expression in all time points checked while 10 μg/mL of dandelion only suppress both expression at 8 and 12 h post-treatment. The in vivo tests showed that the DAE inhibited the expression of TNF-α and ICAM-1 in a time-dependent manner. All results suggest that the endothelium may use as as a possible target of dandelion for anti-inflammation.

  18. Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia

    International Nuclear Information System (INIS)

    Frechou, M.; Beray-Berthat, V.; Plotkine, M.; Marchand-Leroux, C.; Margaill, I.; Raynaud, J.S.; Gombert, F.; Lancelot, E.; Ballet, S.; Robert, P.; Louin, G.; Meriaux, S.

    2013-01-01

    Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nano-particular contrast agent P03011, an USPIO (ultra-small superparamagnetic iron oxide) conjugated to a peptide that targets VCAM-1 (vascular cell adhesion molecule-1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM-1 with MRI after cerebral ischemia in mouse. The time course of VCAM-1 expression was first examined by immunohistochemistry in our model of cerebral ischemia-reperfusion. Secondly, P03011 or non-targeted USPIO P03007 were injected 5 h after ischemia (100 mmol iron kg -1 ; i.v.) and in vivo and ex vivo MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM-1. VCAM-1 expression was significantly up-regulated 24 h after ischemia in our model. In animals receiving P03011, both in vivo and ex vivo MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co-localization of the targeted USPIO and VCAM-1. This study demonstrates that VCAM-1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage. (authors)

  19. Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

    Science.gov (United States)

    Jansson, Keith H; Castillo, Deborah G; Morris, Joseph W; Boggs, Mary E; Czymmek, Kirk J; Adams, Elizabeth L; Schramm, Lawrence P; Sikes, Robert A

    2014-01-01

    Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two auxiliary beta (β) subunits with inherent cell adhesion molecule (CAM) functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs, while interacting putatively with other prominent neural CAMs. Furthermore, beta-2 exhibits elevated mRNA and protein levels in highly metastatic and castrate-resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta-2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI and subsequent PCa metastasis. The objective of this study was to determine the effect of beta-2 expression on PCa cell neurotropic metastasis associated behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed neurotropic effects utilizing our novel ex vivo organotypic spinal cord co-culture model, and performed functional assays with neural matrices and atomic force microscopy. With increased beta-2 expression, PCa cells display a trend of enhanced association with nerve axons. On laminin, a neural CAM, overexpression of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit marked binding affinity to laminin relative to LNECFP controls, and recombinant beta-2 ectodomain elicits more binding events to laminin than BSA control. Functional overexpression of VSSC

  20. Serum carcinoembryonic antigen-related cell adhesion molecule 1 level in postmenopausal women: correlation with β-catenin and bone mineral density.

    Science.gov (United States)

    Ma, C; Shuai, B; Shen, L; Yang, Y P; Xu, X J; Li, C G

    2016-04-01

    Many epidemiological studies have shown that in some tumors carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and β-catenin appear to be related. However, it remains to be established whether CEACAM1 is related to β-catenin in osteoporosis. Here, we reveal that CEACAM1 might influence the canonical Wnt/β-catenin pathway to modulate bone metabolism in postmenopausal osteoporosis. The aim of this study is to assess the serum level of CEACAM1 in postmenopausal women and its correlation with β-catenin and bone mineral density (BMD). The BMD was measured at the lumbar spine (L1-L4) or the femoral neck using dual-energy X-ray absorptiometry (DXA). Serum CEACAM1, β-catenin, receptor activator of nuclear factor kappa-B (RANKL), osteoprotegerin (OPG), β-isomerized C-terminal crosslinking of type I collagen (β-CTX), intact N-terminal propeptide of type I collagen (PINP), estradiol, and insulin were measured in 350 postmenopausal women. Patients were divided according to lumbar spine or femur neck T-scores into osteoporosis (group I), osteopenia (group II), and normal bone mineral density, the latter serving as control. Serum CEACAM1 levels were significantly lower in group I and II compared to those in control subjects (P < 0.001). Serum CEACAM1 levels correlated positively with β-catenin and BMD, but correlated negatively to the ratio between RANKL and OPG. This study provides evidence that decreased serum CEACAM1 levels are related to low BMD in postmenopausal women, and that serum CEACAM1 levels correlated positively to β-catenin. It suggests that CEACAM1 might influence the canonical Wnt/β-catenin pathway to modulate bone metabolism.

  1. EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

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    Chih-Yeu Fang

    2015-01-01

    Full Text Available (−-Epigallocatechin-3-gallate (EGCG, a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC, yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

  2. miR156a Mimic Represses the Epithelial-Mesenchymal Transition of Human Nasopharyngeal Cancer Cells by Targeting Junctional Adhesion Molecule A.

    Directory of Open Access Journals (Sweden)

    Yunhong Tian

    Full Text Available MicroRNAs (miRNAs have been documented as having an important role in the development of cancer. Broccoli is very popular in large groups of the population and has anticancer properties. Junctional adhesion molecule A (JAMA is preferentially concentrated at tight junctions and influences cell morphology and migration. Epithelial-mesenchymal transition (EMT is a developmental program associated with cancer progression and metastasis. In this study we aimed to investigate the role of miRNAs from broccoli in human nasopharyngeal cancer (NPC. We demonstrated that a total of 84 conserved miRNAs and 184 putative novel miRNAs were found in broccoli by sequencing technology. Among these, miR156a was expressed the most. In addition, synthetic miR156a mimic inhibited the EMT of NPC cells in vitro. Furthermore, it was confirmed that JAMA was the target of miR156a mimic as validated by 3' UTR luciferase reporter assays and western blotting. Knockdown of JAMA was consistent with the effects of miR156a mimic on the EMT of NPC, and the up-regulation of JAMA could partially restore EMT repressed by miR156a mimic. In conclusion, these results indicate that the miR156a mimic inhibits the EMT of NPC cells by targeting the 3' UTR of JAMA. These miRNA profiles of broccoli provide a fundamental basis for further research. Moreover, the discovery of miR156a may have clinical implications for the treatment of patients with NPC.

  3. Reduction of intercellular adhesion molecule 1 may play a role in anti-inflammatory effect of hyaluronic acid in a rat model of severe non-bacterial cystitis.

    Science.gov (United States)

    Shao, Yuan; Lu, Guo-liang; Shen, Zhou-Jun; He, Hong-chao

    2013-06-01

    To evaluate the impact of intercellular adhesion molecule 1 (ICAM-1) in hyaluronic acid (HA) therapy in rats model of severe non-bacterial cystitis. Cystitis models in Sprague-Dawley female rats were produced by combination of intraperitoneal cyclophosphamide (CYP) with intravesical protamine/lipopolysaccharide (PS/LPS). HA or heparin (0.5 ml) was introduced intravesically to rats' bladders followed PS/LPS. Bladder tissue was prepared for histology including mast cell presence and measurement of ICAM-1, tumor necrosis factor (TNF)-α, and interleukin 6 (IL-6). Cystitis model using intraperitoneal CYP and intravesical SP/LPS showed serious inflammation, higher mast cell count with elevated ICAM-1, TNF-α, and IL-6 levels. After intravesical heparin or HA treatment, incidence of grades 3-4 bladder inflammation and tissue ICAM-1 level were only significantly lower in HA group (P = 0.017, P = 0.021, respectively), but not in heparin group (P = 0.12, P = 0.798, respectively). Remarkably lower level of TNF-α (P = 0.003) and ICAM-1 (P = 0.006) was detected in HA-treated rats compared with heparin-treated rats. Inflammation grade and ICAM-1 level had strong correlation (P < 0.001). IL-6 level after HA or heparin instillation had no difference. Intravesical administration of HA decreased the severity of bladder inflammation, mast cell presence, and levels of ICAM-1 and TNF-α in a rat model of severe non-bacterial cystitis; its effect was more obvious than that of heparin. Reduction of ICAM-1 may play a role in the anti-inflammatory effect of HA.

  4. Long-term impact of radiation on plasma concentrations of cytokines (IL-1 and IL-6) and adhesion molecules (ICAM-1 and P-selectin) in Chernobyl clean-up workers from Latvia

    International Nuclear Information System (INIS)

    Kurjane, N.; Kirsfinks, M.; Hagina, E.; Socnevs, A.

    2001-01-01

    Study was undertaken to evaluate plasma concentrations of interleukin-1beta (IL-1), interleukin-6 (IL-6), and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and P-selectin in persons who participated in the clean-up work of the Chernobyl NPP explosion aftereffects. 40 Chernobyl clean-up workers suffering from most common neurological diseases - polyneuropathy and encephalopathy, and 40 healthy blood donors were analyzed for plasma levels of IL-6, IL1-β, sICAM-1 and sP-selectin 13 years after the accident. The documented external radiation dosage to the investigated Chernobyl clean-up workers was exposed from 0,009 to 0,28 Gy. Significantly elevated plasma concentrations of IL-6 and P-selectin but not of IL-1β were found in Chernobyl clean-up labourers as compared to those in healthy blood donors. (p<0.01). There was no obvious association of cytokine and adhesion molecule levels with radiation doses, as individuals working in the Chernobyl area in 1986 at a time when the external radiation exposure was higher revealed similar plasma concentrations if compared to those of a later period of time (1987-1990). (authors)

  5. NCAM-associated polysialic acid on ciliary ganglion neurons is regulated by polysialytransferase levels and interaction with muscle.

    Science.gov (United States)

    Brusés, J L; Oka, S; Rutishauser, U

    1995-12-01

    NCAM in its high polysialic acid (PSA) form is expressed on chick hindlimb motoneurons during their growth, and then decreases at about the time that synaptogenesis is completed. In order to characterize this regulation at the cell and molecular level, the present studies use the chick ciliary ganglion (CG) system, which constitutes a homogeneous and developmentally synchronized population of motoneurons that can be used for in vitro studies. Levels of PSA in the CG were evaluated both by SDS-PAGE immunoblot analysis of total NCAM and by pulse radiolabeling of newly synthesized NCAM. Up- and downregulation of PSA expression on newly synthesized NCAM in the CG was found to be closely correlated with in vivo innervation and synaptogenesis, respectively. Moreover, the downregulation observed at synaptogenesis was prevented by in vivo blockade of neuromuscular activity with alpha-bungarotoxin. The developmental regulation of PSA expression was found to coincide precisely with an increase and decrease in levels of specific polysialyltransferase activity. By contrast, the expression of the VASE exon in NCAM, which in CNS is temporally correlated with PSA downregulation, was not expressed in the CG. Cocultures of CG neurons with myotubes were used to provide direct evidence that neuron-muscle interaction can cause a specific downregulation of both neuronal PSA and polysialyltransferase activity.

  6. Downregulation of Melanoma Cell Adhesion Molecule (MCAM/CD146) Accelerates Cellular Senescence in Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Jin, Hye Jin; Kwon, Ji Hye; Kim, Miyeon; Bae, Yun Kyung; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Jeon, Hong Bae

    2016-04-01

    Therapeutic applications of mesenchymal stem cells (MSCs) for treating various diseases have increased in recent years. To ensure that treatment is effective, an adequate MSC dosage should be determined before these cells are used for therapeutic purposes. To obtain a sufficient number of cells for therapeutic applications, MSCs must be expanded in long-term cell culture, which inevitably triggers cellular senescence. In this study, we investigated the surface markers of human umbilical cord blood-derived MSCs (hUCB-MSCs) associated with cellular senescence using fluorescence-activated cell sorting analysis and 242 cell surface-marker antibodies. Among these surface proteins, we selected the melanoma cell adhesion molecule (MCAM/CD146) for further study with the aim of validating observed expression differences and investigating the associated implications in hUCB-MSCs during cellular senescence. We observed that CD146 expression markedly decreased in hUCB-MSCs following prolonged in vitro expansion. Using preparative sorting, we found that hUCB-MSCs with high CD146 expression displayed high growth rates, multilineage differentiation, expression of stemness markers, and telomerase activity, as well as significantly lower expression of the senescence markers p16, p21, p53, and senescence-associated β-galactosidase, compared with that observed in hUCB-MSCs with low-level CD146 expression. In contrast, CD146 downregulation with small interfering RNAs enhanced the senescence phenotype. In addition, CD146 suppression in hUCB-MSCs caused downregulation of other cellular senescence regulators, including Bmi-1, Id1, and Twist1. Collectively, our results suggest that CD146 regulates cellular senescence; thus, it could be used as a therapeutic marker to identify senescent hUCB-MSCs. One of the fundamental requirements for mesenchymal stem cell (MSC)-based therapies is the expansion of MSCs during long-term culture because a sufficient number of functional cells is required

  7. Endothelial Cell-Selective Adhesion Molecule Expression in Hematopoietic Stem/Progenitor Cells Is Essential for Erythropoiesis Recovery after Bone Marrow Injury.

    Science.gov (United States)

    Sudo, Takao; Yokota, Takafumi; Okuzaki, Daisuke; Ueda, Tomoaki; Ichii, Michiko; Ishibashi, Tomohiko; Isono, Tomomi; Habuchi, Yoko; Oritani, Kenji; Kanakura, Yuzuru

    2016-01-01

    Numerous red blood cells are generated every second from proliferative progenitor cells under a homeostatic state. Increased erythropoietic activity is required after myelo-suppression as a result of chemo-radio therapies. Our previous study revealed that the endothelial cell-selective adhesion molecule (ESAM), an authentic hematopoietic stem cell marker, plays essential roles in stress-induced hematopoiesis. To determine the physiological importance of ESAM in erythroid recovery, ESAM-knockout (KO) mice were treated with the anti-cancer drug, 5-fluorouracil (5-FU). ESAM-KO mice experienced severe and prolonged anemia after 5-FU treatment compared to wild-type (WT) mice. Eight days after the 5-FU injection, compared to WT mice, ESAM-KO mice showed reduced numbers of erythroid progenitors in bone marrow (BM) and spleen, and reticulocytes in peripheral blood. Megakaryocyte-erythrocyte progenitors (MEPs) from the BM of 5-FU-treated ESAM-KO mice showed reduced burst forming unit-erythrocyte (BFU-E) capacities than those from WT mice. BM transplantation revealed that hematopoietic stem/progenitor cells from ESAM-KO donors were more sensitive to 5-FU treatment than that from WT donors in the WT host mice. However, hematopoietic cells from WT donors transplanted into ESAM-KO host mice could normally reconstitute the erythroid lineage after a BM injury. These results suggested that ESAM expression in hematopoietic cells, but not environmental cells, is critical for hematopoietic recovery. We also found that 5-FU treatment induces the up-regulation of ESAM in primitive erythroid progenitors and macrophages that do not express ESAM under homeostatic conditions. The phenotypic change seen in macrophages might be functionally involved in the interaction between erythroid progenitors and their niche components during stress-induced acute erythropoiesis. Microarray analyses of primitive erythroid progenitors from 5-FU-treated WT and ESAM-KO mice revealed that various signaling

  8. Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) Is Elevated in Bronchoalveolar Lavage Fluid of Patients with Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Attia, Engi F; Jolley, Sarah E; Crothers, Kristina; Schnapp, Lynn M; Liles, W Conrad

    2016-01-01

    Pulmonary vascular endothelial activation has been implicated in acute respiratory distress syndrome (ARDS), yet little is known about the presence and role of endothelial activation markers in the alveolar space in ARDS. We hypothesized that endothelial activation biomarkers would be differentially expressed in bronchoalveolar lavage fluid from patients with ARDS compared with healthy volunteers, and that biomarker concentrations would be associated with ARDS severity. We performed a cross-sectional analysis of data from 26 intubated patients with ARDS undergoing evaluation for clinically suspected ventilator-associated pneumonia and five healthy volunteers. Patients underwent bronchoalveolar lavage a median of five days after intubation. Healthy volunteers also underwent bronchoalveolar lavage. Endothelial activation biomarkers (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble endothelial selectin [sESEL], angiopoietin-1 [Ang-1] and angiopoietin-2 [Ang-2]) were measured in bronchoalveolar lavage fluid. Clinically suspected ventilator-associated pneumonia was confirmed with microbiologic culture data. Patients with ARDS had significantly higher median sVCAM-1 concentrations in the bronchoalveolar lavage fluid compared with healthy volunteers (985 vs 119 pg/mL, p = 0.03). Additionally, there was a trend toward greater bronchoalveolar lavage fluid sVCAM-1 concentrations among patients with moderate/severe compared to mild ARDS (1395 vs 209 pg/mL, p = 0.06). We did not detect significant differences in bronchoalveolar lavage fluid levels of sESEL, Ang-1 or Ang-2 between patients with ARDS and healthy volunteers. Median bronchoalveolar lavage fluid biomarker levels did not differ between patients with and without microbiologically-confirmed ventilator-associated pneumonia. sVCAM-1 concentrations were significantly higher in the bronchoalveolar lavage fluid of patients with ARDS compared to healthy controls, and tended to be higher in moderate/severe ARDS

  9. Extracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) and correlations with clinical staging in euthymic bipolar disorder.

    Science.gov (United States)

    Reininghaus, Eva Z; Lackner, Nina; Birner, Armin; Bengesser, Susanne; Fellendorf, Frederike T; Platzer, Martina; Rieger, Alexandra; Queissner, Robert; Kainzbauer, Nora; Reininghaus, Bernd; McIntyre, Roger S; Mangge, Harald; Zelzer, Sieglinde; Fuchs, Dietmar; Dejonge, Silvia; Müller, Norbert

    2016-03-01

    Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported. The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters. MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2)  = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2)  = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2)  = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms. A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the

  10. Conserved surface residues on the feline calicivirus (FCV) capsid are essential for interaction with its receptor feline junctional adhesion molecule A (fJAM-A).

    Science.gov (United States)

    Lu, Zhengchun; Ledgerwood, Emily D; Hinchman, Meleana M; Dick, Robert; Parker, John S L

    2018-01-31

    Host cell surface receptors are required for attachment, binding, entry and infection by nonenveloped viruses. Receptor binding can induce conformational changes in the viral capsid and/or the receptor that couple binding with downstream events in the viral life cycle (intracellular signaling, endocytosis and trafficking, and membrane penetration). Virus-receptor interactions also influence viral spread and pathogenicity. The interaction between feline calicivirus (FCV) and its receptor feline Junctional Adhesion Molecule A (fJAM-A) on host cells is required for infection and induces irreversible, inactivating conformational changes in the capsid of some viral strains. Cryo-EM structures of FCV bound to fJAM-A showed several possible virus-receptor interactions. However, the specific residues on the viral capsid required for binding are not known. Capsid residues that may be involved in post-binding events have been implicated by isolation of soluble receptor-resistant (srr) mutants in which changes in the capsid protein sequence change the capacity of such srr mutants to be inactivated upon incubation with soluble fJAM-A. To clarify which residues on the surface of FCV are required for its interaction with fJAM-A, and to potentially identify residues required for post-receptor binding events, we used the existing atomic resolution structures of FCV and the FCV-fJAM-A cryo-EM structures to select 14 capsid residues for mutation and preparation of recombinant viral capsids. Using this approach, we identified residues on the FCV capsid that are required for fJAM-A binding and other residues not required for binding, but required for infection that are likely important for subsequent post-binding events. IMPORTANCE Feline calicivirus (FCV) is a common cause of mild upper respiratory disease in cats. Some FCV isolates can cause virulent systemic disease. The genetic determinants of virulence for FCV are unknown. We previously found that virulent FCV isolates have

  11. Combined Treatment with Amlodipine and Atorvastatin Calcium Reduces Circulating Levels of Intercellular Adhesion Molecule-1 and Tumor Necrosis Factor-α in Hypertensive Patients with Prediabetes.

    Science.gov (United States)

    Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

    2016-01-01

    To assess the effect of amlodipine and atorvastatin on intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α expression, as endothelial function and inflammation indicators, respectively, in hypertensive patients with and without prediabetes. Forty-five consecutive patients with hypertension, diagnosed according to JNC7, were divided into two groups based on the presence (HD group, n = 23) or absence (H group, n = 22) of prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose tolerance (IGT) and fasting glucose tests. All patients simultaneously underwent 12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium combination (5/10 mg; Hisun-Pfizer Pharmaceuticals Co. Ltd). Serum isolated before and after treatment from overnight fasting blood samples was analyzed by ELISA. In the HD and H groups after vs. before 12-week amlodipine/atorvastatin treatment, there were significantly (all P < 0.01) lower levels of ICAM-1 (3.06 ± 0.34 vs. 4.07 ± 0.70 pg/ml; 3.26 ± 0.32 vs. 3.81 ± 0.60 pg/ml, respectively) and TNF-α (78.71 ± 9.19 vs. 110.94 ± 10.71 pg/ml; 80.95 ± 9.33 vs. 101.79 ± 11.72 pg/ml, respectively), with more pronounced reductions in HD vs. H group (ICAM-1Δ: 1.01 ± 0.80 vs. 0.55 ± 0.64 pg/ml, respectively, P = 0.037; TNF-αΔ: 32.23 ± 14.33 vs. 20.84 ± 14.89 pg/ml, respectively, P = 0.011), independent of the blood pressure (BP) and cholesterol level reduction. Amlodipine/atorvastatin improved endothelial function and inflammation, as reflected by lower circulating levels of ICAM-1 and TNF-α, more prominently in hypertensives with than without prediabetes. Starting statin treatment before overt diabetes in hypertensives might thus improve cardiovascular outcomes.

  12. 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

  13. Exploring Functional β-Cell Heterogeneity In Vivo Using PSA-NCAM as a Specific Marker

    Science.gov (United States)

    Karaca, Melis; Castel, Julien; Tourrel-Cuzin, Cécile; Brun, Manuel; Géant, Anne; Dubois, Mathilde; Catesson, Sandra; Rodriguez, Marianne; Luquet, Serge; Cattan, Pierre; Lockhart, Brian; Lang, Jochen; Ktorza, Alain

    2009-01-01

    Background The mass of pancreatic β-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous β-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of β-cells and investigated their physiological relevance in increased insulin demand conditions in rats. Methods Two rat β-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. βhigh and βlow-cells. Insulin release, Ca2+ movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, βhigh and βlow-cell distribution and functionality were investigated in animal models with decreased or increased β-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. Results We show that β-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike βlow-cells, βhigh-cells express functional β-cell markers and are highly responsive to various insulin secretagogues. Whereas βlow-cells represent the main population in diabetic pancreas, an increase in βhigh-cells is associated with gain of function that follows sustained glucose overload. Conclusion Our data show that a functional heterogeneity of β-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in β-cell defects in type 2 diabetes. PMID:19440374

  14. Exploring functional beta-cell heterogeneity in vivo using PSA-NCAM as a specific marker.

    Directory of Open Access Journals (Sweden)

    Melis Karaca

    Full Text Available BACKGROUND: The mass of pancreatic beta-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous beta-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of beta-cells and investigated their physiological relevance in increased insulin demand conditions in rats. METHODS: Two rat beta-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. beta(high and beta(low-cells. Insulin release, Ca(2+ movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, beta(high and beta(low-cell distribution and functionality were investigated in animal models with decreased or increased beta-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. RESULTS: We show that beta-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike beta(low-cells, beta(high-cells express functional beta-cell markers and are highly responsive to various insulin secretagogues. Whereas beta(low-cells represent the main population in diabetic pancreas, an increase in beta(high-cells is associated with gain of function that follows sustained glucose overload. CONCLUSION: Our data show that a functional heterogeneity of beta-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in beta-cell defects in type 2 diabetes.

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

    DEFF Research Database (Denmark)

    Kraev, Igor; Henneberger, Christian; Rossetti, Clara

    2011-01-01

    a homophilic trans-binding site in Ig2 and binds to Ig3--was developed as a tool for studying NCAM's trans-interactions. In this study, we investigated plannexin's ability to affect neural plasticity and memory formation. We found that plannexin facilitates neurite outgrowth in primary hippocampal neuronal...... cultures and improves spatial learning in rats, both under basal conditions and under conditions involving a deficit in a key plasticity-promoting posttranslational modification of NCAM, its polysialylation. We also found that plannexin enhances excitatory synaptic transmission in hippocampal area CA1...

  16. Differential effects of fenofibrate versus atorvastatin on the concentrations of E-selectin and vascular cellular adhesion molecule-1 in patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia: a randomized cross-over trial

    Directory of Open Access Journals (Sweden)

    Otto Carsten

    2003-12-01

    Full Text Available Abstract Background Diabetic dyslipoproteinemia is characterized by hypertriglyceridemia, low HDL-cholesterol and often elevated LDL-cholesterol and is a strong risk factor for atherosclerosis. Adhesion molecule levels are elevated both in hyperlipoproteinemia and diabetes mellitus. It is unclear whether fibrate or statin therapy has more beneficial effects on adhesion molecule concentrations. Methods Atorvastatin (10 mg/d was compared to fenofibrate (200 mg/d each for 6 weeks separated by a 6 week washout period in 11 patients (6 male, 5 female; 61.8 ± 8.2 years; body mass index 29.8 ± 3.1 kg/m2 with type 2 diabetes mellitus (HbA1c 7.3 ± 1.1 % and mixed hyperlipoproteinemia using a randomized, cross-over design. Fasting blood glucose, HbA1c, lipid parameters, E-selectin, ICAM-1, VCAM-1, and fibrinogen concentrations were determined before and after each drug. Results Glucose and HbA1c concentrations remained unchanged during the whole study period. LDL cholesterol was reduced during atorvastatin therapy, triglycerides were lowered more effectively with fenofibrate. Comparison of pre- and postreatment concentrations of E-selectin showed a reduction during atorvastatin (-7 %, p = 0.11 and fenofibrate (-10 %, p Conclusions In addition to the different beneficial effects on lipid metabolism, both drugs appear to lower adhesion molecule plasma concentrations in a different manner in patients with type 2 diabetes and mixed hyperlipoproteinemia. Our observations should be confirmed in a larger cohort of such patients.

  17. Polysialylation of NCAM correlates with onset and termination of seasonal spermatogenesis in roe deer.

    Science.gov (United States)

    Hänsch, Manka; Simon, Peter; Schön, Jennifer; Kaese, Miriam; Braun, Beate C; Jewgenow, Katarina; Göritz, Franz; Küpper, Julia; Ahmadvand, Negah; Geyer, Rudolf; Middendorff, Ralf; Müller, Karin; Galuska, Sebastian P

    2014-06-01

    Roe deer (Capreolus capreolus) are seasonal breeders and cyclic structural changes of roe bucks' testis come along with a totally arrested (winter) and a highly activated spermatogenesis (summer). For this reason, roe buck represents an interesting model to study general mechanisms of initiation and termination of spermatogenesis. We investigated if polysialic acid (polySia)-a linear homopolymer of α2,8-linked sialic acids, which could act as a negative regulator of cell-cell adhesion-might be involved in the activation and/or inactivation of spermatogenesis. To address this point, testis samples of adult male roe deer were collected at different time point of the year. Intriguingly, we observed that polySia attached to the neural cell adhesion molecule was enhanced during the onset of spermatogenesis in April. In addition, polySia was highly expressed in December. Predominantly, polySia was detectable between Sertoli cells and spermatogonia in the basal regions of testicular tubules and in the adluminal part of Sertoli cells. Interestingly, similar polySia distributions were observed during early testis development of other mammalians when gonocytes (p