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Sample records for adhesion molecule-1 pecam-1

  1. Vascular endothelial platelet endothelial cell adhesion molecule 1 (PECAM-1) regulates advanced metastatic progression

    PubMed Central

    DeLisser, Horace; Liu, Yong; Desprez, Pierre-Yves; Thor, Ann; Briasouli, Paraskevei; Handumrongkul, Chakrapong; Wilfong, Jonathon; Yount, Garret; Nosrati, Mehdi; Fong, Sylvia; Shtivelman, Emma; Fehrenbach, Melane; Cao, Gaoyuan; Moore, Dan H.; Nayak, Shruti; Liggitt, Denny; Kashani-Sabet, Mohammed; Debs, Robert

    2010-01-01

    Most patients who die from cancer succumb to treatment-refractory advanced metastatic progression. Although the early stages of tumor metastasis result in the formation of clinically silent micrometastatic foci, its later stages primarily reflect the progressive, organ-destructive growth of already advanced metastases. Early-stage metastasis is regulated by multiple factors within tumor cells as well as by the tumor microenvironment (TME). In contrast, the molecular determinants that control advanced metastatic progression remain essentially uncharacterized, precluding the development of therapies targeted against it. Here we show that the TME, functioning in part through platelet endothelial cell adhesion molecule 1 (PECAM-1), drives advanced metastatic progression and is essential for progression through its preterminal end stage. PECAM-1–KO and chimeric mice revealed that its metastasis-promoting effects are mediated specifically through vascular endothelial cell (VEC) PECAM-1. Anti–PECAM-1 mAb therapy suppresses both end-stage metastatic progression and tumor-induced cachexia in tumor-bearing mice. It reduces proliferation, but not angiogenesis or apoptosis, within advanced tumor metastases. Because its antimetastatic effects are mediated by binding to VEC rather than to tumor cells, anti–PECAM-1 mAb appears to act independently of tumor type. A modified 3D coculture assay showed that anti–PECAM-1 mAb inhibits the proliferation of PECAM-1–negative tumor cells by altering the concentrations of secreted factors. Our studies indicate that a complex interplay between elements of the TME and advanced tumor metastases directs end-stage metastatic progression. They also suggest that some therapeutic interventions may target late-stage metastases specifically. mAb-based targeting of PECAM-1 represents a TME-targeted therapeutic approach that suppresses the end stages of metastatic progression, until now a refractory clinical entity. PMID:20926749

  2. Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits low density lipoprotein-induced signaling in platelets.

    PubMed

    Relou, Ingrid A M; Gorter, Gertie; Ferreira, Irlando Andrade; van Rijn, Herman J M; Akkerman, Jan-Willem N

    2003-08-29

    At physiological concentrations, low density lipoprotein (LDL) increases the sensitivity of platelets to aggregation- and secretion-inducing agents without acting as an independent activator of platelet functions. LDL sensitizes platelets by inducing a transient activation of p38MAPK, a Ser/Thr kinase that is activated by the simultaneous phosphorylation of Thr180 and Tyr182 and is an upstream regulator of cytosolic phospholipase A2 (cPLA2). A similar transient phosphorylation of p38MAPK is induced by a peptide mimicking amino acids 3359-3369 in apoB100 called the B-site. Here we report that the transient nature of p38MAPK activation is caused by platelet endothelial cell adhesion molecule 1 (PECAM-1), a receptor with an immunoreceptor tyrosine-based inhibitory motif. PECAM-1 activation by cross-linking induces tyrosine phosphorylation of PECAM-1 and a fall in phosphorylated p38MAPK and cPLA2. Interestingly, LDL and the B-site peptide also induce tyrosine phosphorylation of PECAM-1, and studies with immunoprecipitates indicate the involvement of c-Src. Inhibition of the Ser/Thr phosphatases PP1/PP2A (okadaic acid) makes the transient p38MAPK activation by LDL and the B-site peptide persistent. Inhibition of Tyr-phosphatases (vanadate) increases Tyr-phosphorylated PECAM-1 and blocks the activation of p38MAPK. Together, these findings suggest that, following a first phase in which LDL, through its B-site, phosphorylates and thereby activates p38MAPK, a second phase is initiated in which LDL activates PECAM-1 and induces dephosphorylation of p38MAPK via activation of the Ser/Thr phosphatases PP1/PP2A. PMID:12775720

  3. Association of susceptibility to septic shock with platelet endothelial cell adhesion molecule-1 gene Leu125Val polymorphism and serum sPECAM-1 levels in sepsis patients.

    PubMed

    Sun, Wei; Li, Fang-Shun; Zhang, Yuan-Huai; Wang, Xiao-Ping; Wang, Chao-Rong

    2015-01-01

    Sepsis is a systemic inflammatory response to infection and includes severe sepsis, septic shock and death. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is one cell adhesion molecule expressed on platelets and leukocytes. It regulates platelet activation and mediates transendothelial migration of leukocytes, thus maintaining the integrity of the vasculature. There are some animal experiments associated with the protective role of PECAM-1 against septic shock. However few host genetic risk factors have been identified for sepsis severity and susceptibility to septic shock. A case-control study was conducted, which included 217 patients with sepsis and 90 control subjects recruited from our hospital. One single nucleotide polymorphisms (SNP) of PECAM-1 gene Leu125Val (C373G) was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum soluble PECAM-1 (sPECAM-1) levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the CG and GG genotypes of SNP in Leu125Val of PECAM-1 (rs668: C>G) was significantly associated with increased susceptibility to septic shock compared with CC genotype in sepsis patients (CG genotype, OR: 2.493, 95% CI: 1.175~5.287, P = 0.016; GG genotype: OR: 3.328, 95% CI: 1.445~7.666, P = 0.004). The serum levels of sPECAM-1 in the sepsis patients (47.1 ± 17.5 ng/ml) were significantly higher than those in the healthy controls (61.3 ± 20.9 ng/ml, P<0.01). Among sepsis patients, the serum levels of sPECAM-1 were significantly higher in CG and GG genotype than in CC genotype. In septic shock patients, nonsurvivors (83.7 ± 12.6 ng/ml, n = 69) had a significantly higher serum sPECAM-1 level than the survivors (76.9 ± 12.7 ng/ml, n = 53) (P<0.01). In conclusion, PECAM-1 Leu125Val polymorphism and its sPECAM-1 levels are associated with sepsis severity and susceptibility to septic shock. PMID:26884965

  4. Association of susceptibility to septic shock with platelet endothelial cell adhesion molecule-1 gene Leu125Val polymorphism and serum sPECAM-1 levels in sepsis patients

    PubMed Central

    Sun, Wei; Li, Fang-Shun; Zhang, Yuan-Huai; Wang, Xiao-Ping; Wang, Chao-Rong

    2015-01-01

    Sepsis is a systemic inflammatory response to infection and includes severe sepsis, septic shock and death. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is one cell adhesion molecule expressed on platelets and leukocytes. It regulates platelet activation and mediates transendothelial migration of leukocytes, thus maintaining the integrity of the vasculature. There are some animal experiments associated with the protective role of PECAM-1 against septic shock. However few host genetic risk factors have been identified for sepsis severity and susceptibility to septic shock. A case-control study was conducted, which included 217 patients with sepsis and 90 control subjects recruited from our hospital. One single nucleotide polymorphisms (SNP) of PECAM-1 gene Leu125Val (C373G) was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum soluble PECAM-1 (sPECAM-1) levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the CG and GG genotypes of SNP in Leu125Val of PECAM-1 (rs668: C>G) was significantly associated with increased susceptibility to septic shock compared with CC genotype in sepsis patients (CG genotype, OR: 2.493, 95% CI: 1.175~5.287, P = 0.016; GG genotype: OR: 3.328, 95% CI: 1.445~7.666, P = 0.004). The serum levels of sPECAM-1 in the sepsis patients (47.1 ± 17.5 ng/ml) were significantly higher than those in the healthy controls (61.3 ± 20.9 ng/ml, P<0.01). Among sepsis patients, the serum levels of sPECAM-1 were significantly higher in CG and GG genotype than in CC genotype. In septic shock patients, nonsurvivors (83.7 ± 12.6 ng/ml, n = 69) had a significantly higher serum sPECAM-1 level than the survivors (76.9 ± 12.7 ng/ml, n = 53) (P<0.01). In conclusion, PECAM-1 Leu125Val polymorphism and its sPECAM-1 levels are associated with sepsis severity and susceptibility to septic shock. PMID:26884965

  5. Fluorescence in situ hybridization mapping of the mouse platelet endothelial cell adhesion molecule-1 (PECAM1) to mouse chromosome 6, region F3-G1

    SciTech Connect

    Xie, Yong; Muller, W.A.

    1996-10-15

    Human platelet/endothelial cell adhesion molecule-1 (PECAM1), an important member of the immunoglobulin gene superfamily, is widely distributed on cells of the vascular system and mediates cellular interactions through both homophilic and heterophilic adhesive mechanisms. The function of PECAM1 in vitro has begun to be understood, but its function in vivo is yet to be established. To study the function of PECAM1 in vivo, its mouse counterpart was identified and its cDNA gene isolated and characterized. In this study, the mouse chromosomal localization was determined for the mouse gene encoding Pecam. Fluorescence in situ hybridization was used to map the Pecam gene on mouse chromosome 6, region F3-G1. 12 refs., 2 figs.

  6. Platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) tyrosine phosphorylation state changes during vasculogenesis in the murine conceptus.

    PubMed Central

    Pinter, E.; Barreuther, M.; Lu, T.; Imhof, B. A.; Madri, J. A.

    1997-01-01

    Vasculogenesis, the differentiation of mesodermal cells to angioblasts and the subsequent formation of blood islands and blood vessels by angioblasts in the conceptus, is a dynamic process modulated, in part, by cell-extracellular matrix and cell-cell interactions in the presence of a variety of growth factors and morphogens. In this report we demonstrate differential tyrosine phosphorylation of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during the formation of blood islands and vessels from clusters of extraembryonic and embryonic angioblasts in the murine conceptus. In addition, we identify the phosphorylation of a particular tyrosine residue in the PECAM-1 cytoplasmic domain, Tyr686, which has the potential of mediating binding to Src homology 2 domain-containing proteins, affecting PECAM-1 cellular localization and endothelial cell migration. Images Figure 1 Figure 2 Figure 3 PMID:9137078

  7. Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) in mechanically stimulated vascular endothelial cells.

    PubMed

    Osawa, M; Masuda, M; Harada, N; Lopes, R B; Fujiwara, K

    1997-03-01

    Fluid flow triggers signal transducing events, modulates gene expression, and remodels cytoskeletal structures in vascular endothelial cells (ECs). However, the primary steps of mechanoreception are still unknown. We have recently reported that a glycoprotein is rapidly tyrosine-phosphorylated in bovine ECs exposed to fluid flow or osmotic shock. Here were cloned a 3.4 kb cDNA encoding this protein and found that this was bovine PECAM-1. The tyrosine-phosphorylation level of PECAM-1 immunoprecipitated from mechanically stimulated bovine or human ECs increased. The PECAM-1 phosphorylation was not induced by reagents that triggered Ca2+ mobilization in ECs. An autophosphorylatable band comigrating with c-Src was co-immunoprecipitated with anti-PECAM-1, and c-Src phosphorylated and bound to a GST fusion protein containing the PECAM-1 cytoplasmic domain. A spliced mRNA form lacking amino acid residues 703-721 in the cytoplasmic domain was also expressed in bovine ECs, c-Src neither phosphorylated nor bound to the fusion protein containing the spliced PECAM-1 cytoplasmic domain which lacked one (Tyr 713) of the six tyrosine residues in the PECAM-1 cytoplasmic domain. These results suggest that the YSEI motif containing Tyr 713 is the Src phosphorylation/binding site. Our study is the first demonstration of inducible tyrosine phosphorylation of PECAM-1 and suggests involvement of PECAM-1 and Src family kinases in the sensing/signal transduction of mechanical stimuli in ECs. PMID:9084985

  8. Absence of Platelet Endothelial Cell Adhesion Molecule 1, PECAM-1/CD31, In Vivo Increases Resistance to Salmonella enterica Serovar Typhimurium in Mice

    PubMed Central

    Lovelace, Michael D.; Yap, May Lin; Yip, Jana; Muller, William; Wijburg, Odilia

    2013-01-01

    PECAM-1/CD31 is known to regulate inflammatory responses and exhibit pro- and anti-inflammatory functions. This study was designed to determine the functional role of PECAM-1 in susceptibility to murine primary in vivo infection with Salmonella enterica serovar Typhimurium and in in vitro inflammatory responses of peritoneal macrophages. Lectin profiling showed that cellular PECAM-1 and recombinant human PECAM-1-Ig chimera contain high levels of mannose sugars and N-acetylglucosamine. Consistent with this carbohydrate pattern, both recombinant human and murine PECAM-1-Ig chimeras were shown to bind S. Typhimurium in a dose-dependent manner in vitro. Using oral and fecal-oral transmission models of S. Typhimurium SL1344 infection, PECAM-1−/− mice were found to be more resistant to S. Typhimurium infection than wild-type (WT) C57BL/6 mice. While fecal shedding of S. Typhimurium was comparable in wild-type and PECAM-1−/− mice, the PECAM-1-deficient mice had lower bacterial loads in systemic organs such as liver, spleen, and mesenteric lymph nodes than WT mice, suggesting that extraintestinal dissemination was reduced in the absence of PECAM-1. This reduced bacterial load correlated with reduced tumor necrosis factor (TNF), interleukin-6 (IL-6), and monocyte chemoattractant protein (MCP) levels in sera of PECAM-1−/− mice. Following in vitro stimulation of macrophages with either whole S. Typhimurium, lipopolysaccharide (LPS) (Toll-like receptor 4 [TLR4] ligand), or poly(I·C) (TLR3 ligand), production of TNF and IL-6 by PECAM-1−/− macrophages was reduced. Together, these results suggest that PECAM-1 may have multiple functions in resistance to infection with S. Typhimurium, including binding to host cells, extraintestinal spread to deeper tissues, and regulation of inflammatory cytokine production by infected macrophages. PMID:23509149

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

    PubMed Central

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

    2016-01-01

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

  10. The adhesion molecule PECAM-1 enhances the TGF-β-mediated inhibition of T cell function.

    PubMed

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

    2016-03-01

    Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that inhibits the proinflammatory functions of T cells, and it is a major factor in abrogating T cell activity against tumors. Canonical TGF-β signaling results in the activation of Smad proteins, which are transcription factors that regulate target gene expression. We found that the cell surface molecule platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitated noncanonical (Smad-independent) TGF-β signaling in T cells. Subcutaneously injected tumor cells that are dependent on TGF-β-mediated suppression of immunity for growth grew more slowly in PECAM-1(-/-) mice than in their wild-type counterparts. T cells isolated from PECAM-1(-/-) mice demonstrated relative insensitivity to the TGF-β-dependent inhibition of interferon-γ (IFN-γ) production, granzyme B synthesis, and cellular proliferation. Similarly, human T cells lacking PECAM-1 demonstrated decreased sensitivity to TGF-β in a manner that was partially restored by reexpression of PECAM-1. Co-incubation of T cells with TGF-β and a T cell-activating antibody resulted in PECAM-1 phosphorylation on an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the recruitment of the inhibitory Src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP-2). Such conditions also induced the colocalization of PECAM-1 with the TGF-β receptor complex as identified by coimmunoprecipitation, confocal microscopy, and proximity ligation assays. These studies indicate a role for PECAM-1 in enhancing the inhibitory functions of TGF-β in T cells and suggest that therapeutic targeting of the PECAM-1-TGF-β inhibitory axis represents a means to overcome TGF-β-dependent immunosuppression within the tumor microenvironment. PMID:26956486

  11. PECAM-1 isoform-specific functions in PECAM-1-deficient brain microvascular endothelial cells.

    PubMed

    DiMaio, Terri A; Sheibani, Nader

    2008-03-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1) is alternatively spliced generating eight isoforms that only differ in the length of their cytoplasmic domain. Multiple isoforms of PECAM-1 are present in the endothelium and their expression levels are regulated during vascular development and angiogenesis. However, the functional significance of PECAM-1 isoforms during these processes remains largely unknown. We recently showed that mouse brain endothelial (bEND) cells prepared from PECAM-1-deficient (PECAM-1-/-) mice differ in their cell adhesive and migratory properties compared to PECAM-1+/+ bEND cells. Here we demonstrate that the restoration of PECAM-1 expression in these cells affects their adhesive and migratory properties in an isoform-specific manner. Expression of Delta14&15 PECAM-1, the predominant isoform present in the mouse endothelium, in PECAM-1-/- bEND cells activated MAPK/ERKs, disrupted adherens junctions, and enhanced cell migration and capillary morphogenesis in Matrigel. In contrast, expression of Delta15 PECAM-1 in PECAM-1-/- bEND cells had minimal effects on their activation of MAPK/ERKs, migration, and capillary morphogenesis. The effects of PECAM-1 on cell adhesive and migratory properties were mediated in an isoform-specific manner, at least in part, through its interactions with intracellular signaling proteins, including SHP-2 and Src. These results suggest that the impact of PECAM-1 on EC adhesion, migration, and capillary morphogenesis is modulated by alternative splicing of its cytoplasmic domain. PMID:18029285

  12. The adaptor protein SAP directly associates with PECAM-1 and regulates PECAM-1-mediated-cell adhesion in T-like cell lines.

    PubMed

    Proust, Richard; Crouin, Catherine; Gandji, Leslie Yewakon; Bertoglio, Jacques; Gesbert, Franck

    2014-04-01

    SAP is a small cytosolic adaptor protein expressed in hematopoietic lineages whose main function is to regulate intracellular signaling pathways induced by the triggering of members of the SLAM receptor family. In this paper, we have identified the adhesion molecule PECAM-1 as a new partner for SAP in a conditional yeast two-hybrid screen. PECAM-1 is an immunoglobulin-like molecule expressed by endothelial cells and leukocytes, which possesses both pro- and anti-inflammatory properties. However, little is known about PECAM-1 functions in T cells. We show that SAP directly and specifically interacts with the cytosolic tyrosine 686 of PECAM-1. We generated different T-like cell lines in which SAP or PECAM-1 are expressed or down modulated and we demonstrate that a diminished SAP expression correlates with a diminished PECAM-1-mediated adhesion. Although SAP has mainly been shown to associate with SLAM receptors, we evidence here that SAP is a new actor downstream of PECAM-1.

  13. The adaptor protein SAP directly associates with PECAM-1 and regulates PECAM-1-mediated-cell adhesion in T-like cell lines.

    PubMed

    Proust, Richard; Crouin, Catherine; Gandji, Leslie Yewakon; Bertoglio, Jacques; Gesbert, Franck

    2014-04-01

    SAP is a small cytosolic adaptor protein expressed in hematopoietic lineages whose main function is to regulate intracellular signaling pathways induced by the triggering of members of the SLAM receptor family. In this paper, we have identified the adhesion molecule PECAM-1 as a new partner for SAP in a conditional yeast two-hybrid screen. PECAM-1 is an immunoglobulin-like molecule expressed by endothelial cells and leukocytes, which possesses both pro- and anti-inflammatory properties. However, little is known about PECAM-1 functions in T cells. We show that SAP directly and specifically interacts with the cytosolic tyrosine 686 of PECAM-1. We generated different T-like cell lines in which SAP or PECAM-1 are expressed or down modulated and we demonstrate that a diminished SAP expression correlates with a diminished PECAM-1-mediated adhesion. Although SAP has mainly been shown to associate with SLAM receptors, we evidence here that SAP is a new actor downstream of PECAM-1. PMID:24388971

  14. The cell-adhesion and signaling molecule PECAM-1 is a molecular mediator of resistance to genotoxic chemotherapy.

    PubMed

    Bergom, Carmen; Goel, Reema; Paddock, Cathy; Gao, Cunji; Newman, Debra K; Matsuyama, Shigemi; Newman, Peter J

    2006-12-01

    Defects in the regulation of apoptotic pathways have been implicated in the emergence of cancers resistant to chemotherapy-induced cell death. Identification of novel signaling molecules that influence cell survival has the potential to facilitate the development of new cancer therapies. The cell adhesion and signaling molecule, PECAM-1, is expressed in many hematopoietic and endothelial cell malignancies, and has previously been shown to suppress mitochondrial-dependent, Bax-mediated apoptosis. The ability of PECAM-1 to influence tumor cell survival following exposure to chemotherapeutic agents, however, is not known. Here we show that, when overexpressed in HEK293 and REN mesothelioma cells, PECAM-1 confers resistance to apoptosis induced by the DNA-damaging chemotherapeutic agent, etoposide. Surprisingly, PECAM-1-mediated cytoprotection was found to be largely independent of its ability to form a signaling complex with the protein-tyrosine phosphatase SHP-2, as virtually no tyrosine phosphorylation of, or SHP-2 association with, PECAM-1 could be detected after etoposide treatment. Furthermore, PECAM-1 retained its ability to protect against chemotherapy-induced apoptosis in cells with SHP-2 levels significantly reduced using SHP-2-specific siRNA, and in cells in which Erk1/2--a downstream effector of SHP-2--had been inhibited. Finally, to determine whether endogenous PECAM-1 confers resistance to chemotherapy-induced apoptosis in lymphoid malignancies and endothelial cells, we used a lentiviral vector to stably express PECAM-1-specific siRNA in the Jurkat leukemia cell line and human umbilical vein endothelial cells (HUVECs). siRNA-expressing Jurkat cells with a 70% reduction of PECAM-1 expression were significantly more sensitive to chemotherapy-induced apoptosis. HUVECs with PECAM-1 expression reduced 75% were also markedly more sensitive to chemotherapy-induced cell death. Taken together, these data demonstrate that endogenous PECAM-1 expression on lymphoid

  15. Platelet endothelial cell adhesion molecule-1 and mechanotransduction in vascular endothelial cells.

    PubMed

    Fujiwara, K

    2006-04-01

    Endothelial cells are known to respond to mechanical forces such as fluid shear stress and cyclic stretch, but elucidating the mechanism for mechanosensing has been difficult. Experimental data indicate that there are probably several sensing mechanisms. We have recently proposed a novel mechanoresponse mechanism that involves platelet endothelial cell adhesion molecule-1 (PECAM-1). When endothelial cells are stimulated by fluid shear stress, PECAM-1 is tyrosine phosphorylated and activates the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling cascade. The same signalling events occurred when we applied pulling force directly on PECAM-1 on the endothelial cell surface using magnetic beads coated with antibodies against the external domain of PECAM-1. These results appear to indicate that PECAM-1 is a mechanotransduction molecule. To our knowledge, this is the first mammalian molecule that is shown to respond to mechanical force directly exerted to it. PMID:16594905

  16. Structural basis for PECAM-1 homophilic binding.

    PubMed

    Paddock, Cathy; Zhou, Dongwen; Lertkiatmongkol, Panida; Newman, Peter J; Zhu, Jieqing

    2016-02-25

    Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa member of the immunoglobulin gene superfamily (IgSF) that is present on the surface of circulating platelets and leukocytes, and highly expressed at the junctions of confluent endothelial cell monolayers. PECAM-1-mediated homophilic interactions, known to be mediated by its 2 amino-terminal immunoglobulin homology domains, are essential for concentrating PECAM-1 at endothelial cell intercellular junctions, where it functions to facilitate diapedesis, maintain vascular integrity, and transmit survival signals into the cell. Given the importance of PECAM-1-mediated homophilic interactions in mediating each of these cell physiological events, and to reveal the nature and orientation of the PECAM-1-PECAM-1 homophilic-binding interface, we undertook studies aimed at determining the crystal structure of the PECAM-1 homophilic-binding domain, which is composed of amino-terminal immunoglobulin homology domains 1 and 2 (IgD1 and IgD2). The crystal structure revealed that both IgD1 and IgD2 exhibit a classical IgSF fold, having a β-sandwich topology formed by 2 sheets of antiparallel β strands stabilized by the hallmark disulfide bond between the B and F strands. Interestingly, despite previous assignment to the C2 class of immunoglobulin-like domains, the structure of IgD1 reveals that it actually belongs to the I2 set of IgSF folds. Both IgD1 and IgD2 participate importantly in the formation of the trans homophilic-binding interface, with a total buried interface area of >2300 Å(2). These and other unique structural features of PECAM-1 allow for the development of an atomic-level model of the interactions that PECAM-1 forms during assembly of endothelial cell intercellular junctions. PMID:26702061

  17. Regulation of platelet biology by platelet endothelial cell adhesion molecule-1.

    PubMed

    Jones, Chris I; Moraes, Leonardo A; Gibbins, Jonathan M

    2012-01-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1), an immunoreceptor tyrosine-based inhibitory motif containing receptor, plays diverse and apparently contradictory roles in regulating the response of platelets to stimuli; inhibiting platelet response to immunoreceptor tyrosine-based activation motif and G protein-coupled receptor signalling following stimulation with collagen, adenosine diphosphate, and thrombin, as well as enhancing integrin outside-in signalling. These dual, and opposing, roles suggest an important and complex role for PECAM-1 in orchestrating platelet response to vascular damage. Indeed, during thrombus formation, the influence of PECAM-1 on the multiple signalling pathways combines leading to a relatively large inhibitory effect on thrombus formation. PMID:22035359

  18. Dimer conformation of soluble PECAM-1, an endothelial marker.

    PubMed

    Jiang, Longguang; Lin, Lin; Li, Rui; Yuan, Cai; Xu, Mingming; Huang, Joy H; Huang, Mingdong

    2016-08-01

    Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a cell surface receptor widely distributed on endothelium and hematopoietic-derived cells, and maintain the integrity of the blood vessels. PECAM-1 is widely recognized as an endothelial cell marker. The homophilic interaction through its extracellular domain of PECAM-1 (soluble PECAM-1, or sPECAM-1) is important to its functions. However, structural details for such dimerization are not fully understood. Here we report the production of recombinant sPECAM-1 in large quantity by Drosophila expression system and the small-angle X-ray diffraction (SAXS) study. The recombinant sPECAM-1 was found to form one population of dimer, but not oligomer, and was able to bind to heparin immobilized on a chip in surface plasmon resonance imaging (SPRi) binding experiments. The results of SAXS demonstrated that sPECAM-1 formed a symmetric homodimer of Ω-shape in solution, and each protomer adopted an extended conformation. The dimer is mediated through the intermolecular interactions through the first N-terminal domain (D1) of sPECAM-1. This model provides new structural information for its homophilic interaction mechanism. PMID:27270333

  19. Platelet PECAM-1 inhibits thrombus formation in vivo.

    PubMed

    Falati, Shahrokh; Patil, Sonali; Gross, Peter L; Stapleton, Michelle; Merrill-Skoloff, Glenn; Barrett, Natasha E; Pixton, Katherine L; Weiler, Harmut; Cooley, Brian; Newman, Debra K; Newman, Peter J; Furie, Barbara C; Furie, Bruce; Gibbins, Jonathan M

    2006-01-15

    Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell surface glycoprotein receptor expressed on a range of blood cells, including platelets, and on vascular endothelial cells. PECAM-1 possesses adhesive and signaling properties, the latter being mediated by immunoreceptor tyrosine-based inhibitory motifs present on the cytoplasmic tail of the protein. Recent studies in vitro have demonstrated that PECAM-1 signaling inhibits the aggregation of platelets. In the present study we have used PECAM-1-deficient mice and radiation chimeras to investigate the function of this receptor in the regulation of thrombus formation. Using intravital microscopy and laser-induced injury to cremaster muscle arterioles, we show that thrombi formed in PECAM-1-deficient mice were larger, formed more rapidly than in control mice, and were more stable. Larger thrombi were also formed in control mice that received transplants of PECAM-1-deficient bone marrow, in comparison to mice that received control transplants. A ferric chloride model of thrombosis was used to investigate thrombus formation in carotid arteries. In PECAM-1-deficient mice the time to 75% vessel occlusion was significantly shorter than in control mice. These data provide evidence for the involvement of platelet PECAM-1 in the negative regulation of thrombus formation. PMID:16166583

  20. Platelet endothelial cell adhesion molecule-1 modulates endothelial cell motility through the small G-protein Rho.

    PubMed

    Gratzinger, Dita; Canosa, Sandra; Engelhardt, Britta; Madri, Joseph A

    2003-08-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1), an immunoglobulin family vascular adhesion molecule, is involved in endothelial cell migration and angiogenesis (1, 2). We found that endothelial cells lacking PECAM-1 exhibit increased single cell motility and extension formation but poor wound healing migration, reminiscent of cells in which Rho activity has been suppressed by overexpressing a GTPase-activating protein (3). The ability of PECAM-1 to restore wound healing migration to PECAM-1-deficient cells was independent of its extracellular domain or signaling via its immunoreceptor tyrosine-based inhibitory motif. PECAM-1-deficient endothelial cells had a selective defect in RhoGTP loading, and inhibition of Rho activity mimicked the PECAM-1-deficient phenotype of increased chemokinetic single cell motility at the expense of coordinated wound healing migration. The wound healing advantage of PECAM-1-positive endothelial cells was not only Rho mediated but pertussis toxin inhibitable, characteristic of migration mediated by heterotrimeric G-protein-linked seven-transmembrane receptor signaling such as signaling in response to the serum sphingolipid sphingosine-1-phosphate (S1P) (4, 5). Indeed, we found that the wound healing defect of PECAM-1 null endothelial cells is minimized in sphingolipid-depleted media; moreover, PECAM-1 null endothelial cells fail to increase their migration in response to S1P. We have also found that PECAM-1 localizes to rafts and that in its absence heterotrimeric G-protein components are differentially recruited to rafts, providing a potential mechanism for PECAM-1-mediated coordination of S1P signaling. PECAM-1 may thus support the effective S1P/RhoGTP signaling required for wound healing endothelial migration by allowing for the spatially directed, coordinated activation of Galpha signaling pathways. PMID:12890700

  1. Lyn and PECAM-1 function as interdependent inhibitors of platelet aggregation.

    PubMed

    Ming, Zhangyin; Hu, Yu; Xiang, Jizhou; Polewski, Peter; Newman, Peter J; Newman, Debra K

    2011-04-01

    Inhibition of platelet responsiveness is important to control pathologic thrombus formation. Platelet-endothelial cell adhesion molecule-1 (PECAM-1) and the Src family kinase Lyn inhibit platelet activation by the glycoprotein VI (GPVI) collagen receptor; however, it is not known whether PECAM-1 and Lyn function in the same or different inhibitory pathways. In these studies, we found that, relative to wild-type platelets, platelets derived from PECAM-1-deficient, Lyn-deficient, or PECAM-1/Lyn double-deficient mice were equally hyperresponsive to stimulation with a GPVI-specific agonist, indicating that PECAM-1 and Lyn participate in the same inhibitory pathway. Lyn was required for PECAM-1 tyrosine phosphorylation and subsequent binding of the Src homology 2 domain-containing phosphatase-2, SHP-2. These results support a model in which PECAM-1/SHP-2 complexes, formed in a Lyn-dependent manner, suppress GPVI signaling. PMID:21297004

  2. Sphingosine 1-phosphate induces platelet/endothelial cell adhesion molecule-1 phosphorylation in human endothelial cells through cSrc and Fyn.

    PubMed

    Huang, Yu-Ting; Chen, Shee-Uan; Chou, Chia-Hong; Lee, Hsinyu

    2008-08-01

    Sphingosine 1-phosphate (S1P) is a multifunctional phospholipid which acts through a specific family of G protein-coupled receptors. Platelet/endothelial cell adhesion molecule-1 (PECAM-1) form trans-homophilic binding at lateral cell border. Upon stimulation, its cytoplasmic tyrosine residues could be phosphorylated and interact with various downstream signaling molecules. In this study, we demonstrated that S1P induced PECAM-1 tyrosine phosphorylation in human umbilical cord vein cells (HUVECs). By pharmacological inhibitors, it was suggested that G(i) and Src family kinases were involved in PECAM-1 phosphorylation. Moreover, cSrc and Fyn siRNA significantly suppressed S1P-induced PECAM-1 phosphorylation. These results suggested that S1P-induced PECAM-1 phosphorylation through G(i) and subsequent cSrc and Fyn. Our findings provide further understanding of S1P and PECAM-1 signaling as well as their functions in endothelial cells. PMID:18502612

  3. SHP-2 phosphatase activity is required for PECAM-1-dependent cell motility.

    PubMed

    Zhu, Jing-Xu; Cao, Gaoyuan; Williams, James T; Delisser, Horace M

    2010-10-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1) has been implicated in endothelial cell motility during angiogenesis. Although there is evidence that SHP-2 plays a role in PECAM-1-dependent cell motility, the molecular basis of the activity of SHP-2 in this process has not been defined. To investigate the requirement of SHP-2 in PECAM-1-dependent cell motility, studies were done in which various constructs of SHP-2 were expressed in cell transfectants expressing PECAM-1. We observed that the levels of PECAM-1 tyrosine phosphorylation and SHP-2 association with PECAM-1 were significantly increased in cells expressing a phosphatase-inactive SHP-2 mutant, suggesting that the level of PECAM-1 tyrosine phosphorylation, and thus SHP-2 binding are regulated in part by bound, catalytically active SHP-2. We subsequently found that expression of PECAM-1 stimulated wound-induced migration and the formation of filopodia (a morphological feature of motile cells). These activities were associated with increased mitogen-activated protein kinase (MAPK) activation and the dephosphorylation of paxillin (an event implicated in the activation of MAPK). The phosphatase-inactive SHP-2 mutant, however, suppressed these PECAM-1-dependent phenomena, whereas the activity of PECAM-1 expressing cells was not altered by expression of wild-type SHP-2 or SHP-2 in which the scaffold/adaptor function had been disabled. Pharmacological inhibition of SHP-2 phosphatase activity also suppressed PECAM-1-dependent motility. Furthermore, PECAM-1 expression also stimulates tube formation, but none of the SHP-2 constructs affected this process. These findings therefore suggest a model for the involvement of SHP-2 in PECAM-1-dependent motility in which SHP-2, recruited by its interaction with PECAM-1, targets paxillin to ultimately activate the MAPK pathway and downstream events required for cell motility. PMID:20631249

  4. Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells.

    PubMed

    Kogata, Naoko; Masuda, Michitaka; Kamioka, Yuji; Yamagishi, Akiko; Endo, Akira; Okada, Masato; Mochizuki, Naoki

    2003-09-01

    Platelet endothelial adhesion molecule-1 (PECAM-1) is a part of intercellular junctions and triggers intracellular signaling cascades upon homophilic binding. The intracellular domain of PECAM-1 is tyrosine phosphorylated upon homophilic engagement. However, it remains unclear which tyrosine kinase phosphorylates PECAM-1. We sought to isolate tyrosine kinases responsible for PECAM-1 phosphorylation and identified Fer as a candidate, based on expression cloning. Fer kinase specifically phosphorylated PECAM-1 at the immunoreceptor tyrosine-based inhibitory motif. Notably, Fer induced tyrosine phosphorylation of SHP-2, which is known to bind to the immunoreceptor tyrosine-based inhibitory motif of PECAM-1, and Fer also induced tyrosine phosphorylation of Gab1 (Grb2-associated binder-1). Engagement-dependent PECAM-1 phosphorylation was inhibited by the overexpression of a kinase-inactive mutant of Fer, suggesting that Fer is responsible for the tyrosine phosphorylation upon PECAM-1 engagement. Furthermore, by using green fluorescent protein-tagged Fer and a time-lapse fluorescent microscope, we found that Fer localized at microtubules in polarized and motile vascular endothelial cells. Fer was dynamically associated with growing microtubules in the direction of cell-cell contacts, where p120catenin, which is known to associate with Fer, colocalized with PECAM-1. These results suggest that Fer localized on microtubules may play an important role in phosphorylation of PECAM-1, possibly through its association with p120catenin at nascent cell-cell contacts. PMID:12972546

  5. Neutrophils lacking platelet-endothelial cell adhesion molecule-1 exhibit loss of directionality and motility in CXCR2-mediated chemotaxis.

    PubMed

    Wu, Yue; Stabach, Paul; Michaud, Michael; Madri, Joseph A

    2005-09-15

    Time-lapsed videomicroscopy was used to study the migration of platelet-endothelial cell adhesion molecule-1-deficient (PECAM-1(-/-)) murine neutrophils undergoing chemotaxis in Zigmond chambers containing IL-8, KC, or fMLP gradients. PECAM-1(-/-) neutrophils failed to translocate up the IL-8, KC, and fMLP gradients. Significant reductions in cell motility and cell spreading were also observed in IL-8 or KC gradients. In wild-type neutrophils, PECAM-1 and F-actin were colocalized at the leading fronts of polarized cells toward the gradient. In contrast, in PECAM-1(-/-) neutrophils, although F-actin also localized to the leading front of migrating cells, F-actin polymerization was unstable, and cycling was remarkably increased compared with that of wild-type neutrophils. This may be due to the decreased cytokine-induced mobilization of the actin-binding protein, moesin, into the cytoskeleton of PECAM-1(-/-) neutrophils. PECAM-1(-/-) neutrophils also exhibited intracellularly dislocalized Src homology 2 domain containing phosphatase 1 (SHP-1) and had less IL-8-induced SHP-1 phosphatase activity. These results suggest that PECAM-1 regulates neutrophil chemotaxis by modulating cell motility and directionality, in part through its effects on SHP-1 localization and activation. PMID:16148090

  6. Platelet endothelial cell adhesion molecule-1 gene 125C/G polymorphism is associated with deep vein thrombosis.

    PubMed

    Li, Gang; Han, Zong-Lin; Dong, He-Gui; Zhang, Xia; Kong, Xiang-Qian; Jin, Xing

    2015-08-01

    Deep vein thrombosis (DVT) is a common disorder that is associated with high morbidity and mortality. Genetic factors have been suggested to influence the predisposition towards thrombosis and the incidence of DVT. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a key adhesion molecule that is involved in platelet function and maintenance of endothelial cell junctions. To date, no studies have examined the association between polymorphisms in PECAM-1 and DVT. The present study analyzed the single nucleotide polymorphisms (SNPs) of PECAM-1, namely Leu125Val (C373G), Asn563Ser (T1688C) and Gly670Arg (C2008T), in Chinese patients with DVT and age-and gender-matched controls, using polymerase chain reaction-restriction fragment length polymorphism analysis. Furthermore, plasma soluble PECAM-1 (sPECAM-1) levels were quantified by ELISA. The results of the present study demonstrated significantly higher genotype and allele frequencies of the Leu125Val polymorphism in PECAM-1 in the DVT group as compared with those in the control group (P<0.05). The plasma levels of sPECAM-1 in the DVT group (83.4 ± 23.5 ng/ml) were also significantly higher as compared with those in the control group (60.4 ± 19.4 ng/ml, P<0.01). In the patients with DVT, plasma levels of sPECAM-1 were significantly higher in those with the Leu/Val and Val/Val genotypes as compared with those possessing the Leu/Leu genotype (P<0.05). The PECAM-1 Leu125Val polymorphism was shown to be associated with an increased risk of DVT and PECAM-1 protein expression levels in venous vessels. In patients with DVT, the PECAM-1 Leu/Val and Val/Val genotypes were associated with delayed thrombus resolution, as determined by thrombus scoring, as compared with that in patients possessing the Leu/Val genotype. In conclusion, the present study indicated that PECAM-1 Leu125Val polymorphism and sPECAM-1 levels may be associated with DVT.

  7. Role of PECAM-1 in radiation-induced liver inflammation.

    PubMed

    Malik, Ihtzaz Ahmed; Stange, Ina; Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens Friedrich; Ellenrieder, Volker; Wolff, Hendrik Andreas

    2015-10-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-dependent decrease in hepatic PECAM-1, corresponding to an increase in intercellular cell adhesion molecule-1 (ICAM-1) (6 hrs) was detected in WT-mice after irradiation. Immunohistologically, an increased number of neutrophil granulocytes (NG) (but not of mononuclear phagocytes) was observed in the liver of WT and PECAM-1-KO mice at 6 hrs after irradiation. The number of recruited NG was higher and prolonged until 24 hrs in KO compared to WT-mice. Correspondingly, a significant induction of hepatic tumour necrosis factor (TNF)-α and CXC-chemokines (KC/CXCL1 interleukin-8/CXCL8) was detected together with an elevation of serum liver transaminases (6-24 hrs) in WT and KO-mice. Likewise, phosphorylation of signal transducer and activator of transcription-3 (STAT-3) was observed in both animal groups after irradiation. The level of all investigated proteins as well as of the liver transaminases was significantly higher in KO than WT-mice. In the cell-line U937, irradiation led to a reduction in PECAM-1 in parallel to an increased ICAM-1 expression. TNF-α-blockage by anti-TNF-α prevented this change in both proteins in cell culture. Radiation-induced stress conditions induce a transient accumulation of granulocytes within the liver by down-regulation/absence of PECAM-1. It suggests that reduction/lack in PECAM-1 may lead to greater and prolonged inflammation which can be prevented by anti-TNFα. PMID:26177067

  8. Identification of the regions of PECAM-1 involved in beta- and gamma-catenin associations.

    PubMed

    Biswas, Purba; Zhang, Jin; Schoenfeld, Jonathan D; Schoenfeld, David; Gratzinger, Dita; Canosa, Sandra; Madri, Joseph A

    2005-04-22

    Platelet endothelial cell adhesion molecule-1 (PECAM-1) binds tyrosine-phosphorylated beta-catenin and modulates beta-catenin localization and sequestration. The biological significance of this interaction, while still unclear, it has been postulated to be involved in modulating adherens junction dynamics in response to perturbants [J. Clin. Invest. 109 (2002) 383]. Here we demonstrate that tyrosine-phosphorylated beta-catenin, and to a lesser extent unphosphorylated beta-catenin, interact with a portion of the cytoplasmic domain of PECAM-1 encoded by exon 15. Using RT-PCR, we obtained products representing alternatively spliced PECAM-1 isoforms from mouse kidney total mRNA and generated PECAM-1-GST constructs expressing full length and naturally occurring alternatively spliced PECAM-1 variants. Co-precipitation assays revealed that the protein sequence encoded by exon 15 is necessary for beta-catenin binding. Transfections using deletion mutants confirmed the importance of the exon 15 sequence in this interaction. In contrast, gamma-catenin-PECAM-1 interactions are thought to be modulated by an as yet undefined PECAM-1 serine phosphorylation and appear to mediate dynamic PECAM-1 intermediate filament cytoskeletal interactions [J. Biol. Chem. 275 (2000) 21435]. Here we demonstrate that the PECAM-1-gamma-catenin interaction occurs via an exon 13-mediated process. GST-pull-down assays illustrated the importance of the exon 13 sequence in this interaction. Further, using site-directed mutagenesis of S(673) to C and D and S(669 and 670) to C, we confirmed the importance of S(673) and its phosphorylation state as a mediator of gamma-catenin-PECAM-1 binding. Our studies define the exons of the PECAM-1 cytoplasmic domain that is involved in mediating these PECAM-1-catenin family member interactions and will allow investigators to better define the biological functions resulting from these interactions. PMID:15766557

  9. Antithrombotic actions of statins involve PECAM-1 signaling.

    PubMed

    Moraes, Leonardo A; Vaiyapuri, Sakthivel; Sasikumar, Parvathy; Ali, Marfoua S; Kriek, Neline; Sage, Tanya; Gibbins, Jonathan M

    2013-10-31

    Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment of coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Because several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1 (platelet endothelial cell adhesion molecule-1), we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signaling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1(-/-) platelets. Activation of PECAM-1 signaling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3K), and diminished PI3K signaling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provide evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs. PMID:24030383

  10. Association of PECAM1/CD31 polymorphisms with cerebral malaria

    PubMed Central

    Ohashi, Jun; Naka, Izumi; Hananantachai, Hathairad; Patarapotikul, Jintana

    2016-01-01

    Platelet/endothelial cell adhesion molecule-1 (PECAM1/CD31), a receptor recognized by P. falciparum-infected red blood cells (iRBCs), on the vascular endothelium has been implicated in mediating cytoadherence in patients with P. falciparum malaria. To examine associations of PECAM1 polymorphisms with cerebral malaria, 11 tag single nucleotide polymorphisms (SNPs) of PECAM1 were analysed for 312 Thai patients with P. falciparum malaria (109 with cerebral malaria and 203 with mild malaria). The rs1122800-C allele was significantly associated with protection from cerebral malaria (P = 0.017), and the rs9912957-A significantly increased the risk for cerebral malaria (P = 0.0065) in malaria patients. Fine-scale mapping using genotyped and imputed SNPs and linkage disequilibrium (LD) analysis revealed that rs1122800 and rs9912957 were located in two distinct LD blocks and were independently associated with cerebral malaria. The rs1122800-C allele was significantly associated with lower expression level of PECAM1 in EBV-transformed lymphoblastoid cell lines (P = 0.045). The present results suggest that PECAM1-mediated cytoadherence of iRBCs to brain endothelium plays a crucial role in the pathogenesis of cerebral malaria. PMID:27335627

  11. Change in platelet endothelial cell adhesion molecule-1 immunoreactivity in the dentate gyrus in gerbils fed a folate-deficient diet.

    PubMed

    Yoo, Ki-Yeon; Hwang, In Koo; Kim, Young Sup; Kwon, Dae Young; Won, Moo Ho

    2008-02-01

    Folate deficiency increases stroke risk. We examined whether folate deficiency affects platelet endothelial cell adhesion molecule-1 (PECAM-1), which is an immunoglobulin-associated cell adhesion molecule and mediates the final common pathway of neutrophil transendothelial migration, in blood vessels in the gerbil dentate gyrus after transient forebrain ischemia. Gerbils were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to common carotid artery occlusion for 5 min. In the control diet (CD)- and FAD-treated sham-operated groups, weak PECAM-1 immunoreactivity was detected in the blood vessels located in the dentate gyrus. PECAM-1 immunoreactivity in both groups was increased by 4 days after ischemic insult. PECAM-1 immunoreactivity in the FAD-treated group was twice as high that in the CD-treated-sham-operated group 4 days after ischemic insult. Western blot analyses showed that the change patterns in PECAM-1 protein levels in the dentate gyrus in both groups after ischemic insult were similar to changes in PECAM-1 immunohistochemistry in the ischemic dentate gyrus. Our results suggest that folate deficiency enhances PECAM-1 in the dentate gyrus induced by transient ischemia.

  12. PECAM-1 Isoforms, eNOS, and Endoglin Axis in Regulation of Angiogenesis

    PubMed Central

    Park, SunYoung; Sorenson, Christine M.; Sheibani, Nader

    2016-01-01

    Vascular development and maintenance of proper vascular function through various regulatory mechanisms are critical to our wellbeing. Delineating the regulatory processes involved in development of vascular system and function is one of the most important topics in human physiology and pathophysiology. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a cell adhesion molecule with proangiogenic and proinflammatory activity, has been subject of numerous studies. Here we will review the important roles PECAM-1 and its isoforms play during angiogenesis, and its molecular mechanisms of action in the endothelium. In the endothelium, PECAM-1 not only plays a role as an adhesion molecule but also participates in intracellular signaling pathways which impact various cell adhesive mechanisms and endothelial nitric oxide (eNOS) expression and activity. In addition, recent studies from our laboratory have revealed an important relationship between PECAM-1 and endoglin expression. Endoglin is an essential molecule during angiogenesis, vascular development and integrity whose expression and activity are compromised in the absence of PECAM-1. Here we will discuss the roles PECAM-1 isoforms may play in modulation of endothelial cell adhesive mechanisms, eNOS and endoglin expression and activity, and angiogenesis. PMID:25976664

  13. PECAM-1 affects GSK-3beta-mediated beta-catenin phosphorylation and degradation.

    PubMed

    Biswas, Purba; Canosa, Sandra; Schoenfeld, David; Schoenfeld, Jonathan; Li, Puyau; Cheas, Lydia C; Zhang, Jin; Cordova, Alfredo; Sumpio, Bauer; Madri, Joseph A

    2006-07-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) regulates a variety of endothelial and immune cell biological responses. PECAM-1-null mice exhibit prolonged and increased permeability after inflammatory insults. We observed that in PECAM-1-null endothelial cells (ECs), beta-catenin remained tyrosine phosphorylated, coinciding with a sustained increase in permeability. Src homology 2 domain containing phosphatase 2 (SHP-2) association with beta-catenin was diminished in PECAM-1-null ECs, suggesting that lack of PECAM-1 inhibits the ability of this adherens junction component to become dephosphorylated, promoting a sustained increase in permeability. beta-Catenin/Glycogen synthase kinase 3 (GSK-3beta) association and beta-catenin serine phosphorylation levels were increased and beta-catenin expression levels were reduced in PECAM-1-null ECs. Glycogen synthase kinase 3 (GSK-3beta) serine phosphorylation (inactivation) was blunted in PECAM-1-null ECs after histamine treatment or shear stress. Our data suggest that PECAM-1 serves as a critical dynamic regulator of endothelial barrier permeability. On stimulation by a vasoactive substance or shear stress, PECAM-1 became tyrosine phosphorylated, enabling recruitment of SHP-2 and tyrosine-phosphorylated beta-catenin to its cytoplasmic domain, facilitating dephosphorylation of beta-catenin, and allowing reconstitution of adherens junctions. In addition, PECAM-1 modulated the levels of beta-catenin by regulating the activity of GSK-3beta, which in turn affected the serine phosphorylation of beta-catenin and its proteosomal degradation, affecting the ability of the cell to reform adherens junctions in a timely fashion. PMID:16816383

  14. PECAM-1 Affects GSK-3β-Mediated β-Catenin Phosphorylation and Degradation

    PubMed Central

    Biswas, Purba; Canosa, Sandra; Schoenfeld, David; Schoenfeld, Jonathan; Li, Puyau; Cheas, Lydia C.; Zhang, Jin; Cordova, Alfredo; Sumpio, Bauer; Madri, Joseph A.

    2006-01-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) regulates a variety of endothelial and immune cell biological responses. PECAM-1-null mice exhibit prolonged and increased permeability after inflammatory insults. We observed that in PECAM-1-null endothelial cells (ECs), β-catenin remained tyrosine phosphorylated, coinciding with a sustained increase in permeability. Src homology 2 domain containing phosphatase 2 (SHP-2) association with β-catenin was diminished in PECAM-1-null ECs, suggesting that lack of PECAM-1 inhibits the ability of this adherens junction component to become dephosphorylated, promoting a sustained increase in permeability. β-Catenin/Glycogen synthase kinase 3 (GSK-3β) association and β-catenin serine phosphorylation levels were increased and β-catenin expression levels were reduced in PECAM-1-null ECs. Glycogen synthase kinase 3 (GSK-3β) serine phosphorylation (inactivation) was blunted in PECAM-1-null ECs after histamine treatment or shear stress. Our data suggest that PECAM-1 serves as a critical dynamic regulator of endothelial barrier permeability. On stimulation by a vasoactive substance or shear stress, PECAM-1 became tyrosine phosphorylated, enabling recruitment of SHP-2 and tyrosine-phosphorylated β-catenin to its cytoplasmic domain, facilitating dephosphorylation of β-catenin, and allowing reconstitution of adherens junctions. In addition, PECAM-1 modulated the levels of β-catenin by regulating the activity of GSK-3β, which in turn affected the serine phosphorylation of β-catenin and its proteosomal degradation, affecting the ability of the cell to reform adherens junctions in a timely fashion. PMID:16816383

  15. Coupling factor 6 downregulates platelet endothelial cell adhesion molecule-1 via c-Src activation and acts as a proatherogenic molecule.

    PubMed

    Kumagai, Akiko; Osanai, Tomohiro; Katoh, Chisato; Tanaka, Makoto; Tomita, Hirofumi; Morimoto, Takeshi; Murakami, Reiichi; Magota, Koji; Okumura, Ken

    2008-09-01

    Coupling factor 6 (CF6), a component of ATP synthase, suppresses the generation of prostacyclin and nitric oxide (NO). Platelet endothelial cell adhesion molecule-1 (PECAM-1) is involved in shear-induced NO production. To investigate the linkage between the actions of CF6 and PECAM-1, we examined the effects of CF6 on PECAM-1 expression and shear-mediated NO release, comparatively with those of angiotensin II (AngII). Treatment of human umbilical vein endothelial cells (HUVEC) and aortic endothelial cells (HAEC) with CF6 at 10(-7)M or AngII at 10(-7)M for 24h suppressed PECAM-1 gene and protein expression. CF6 or AngII activated c-Src at 15 min in HUVEC, and blockade of c-Src with PP1, its specific inhibitor, restored them. Efrapeptin, an inhibitor of ATPase, attenuated CF6-induced suppression of PECAM-1 gene expression by blockade of acidification, whereas superoxide dismutase or apocinin, an inhibitor of NADPH oxidase, blocked AngII-induced suppression of PECAM-1. Exposure of the cells to shear stress at 25 dynes/cm(2) for 30 min enhanced phosphorylation of eNOS at Ser(1177) and NO release. Pretreatment with CF6 or AngII for 24h attenuated them in HUVEC and HAEC. These suggest that CF6 downregulates PECAM-1 expression via c-Src activation and attenuates shear-induced NO release presumably by suppressing eNOS phosphorylation. PMID:18243211

  16. Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology.

    PubMed

    Newman, Peter J; Newman, Debra K

    2003-06-01

    Recent studies of platelet endothelial cell adhesion molecule-1 (PECAM-1 [CD31])-deficient mice have revealed that this molecule plays an important role in controlling the activation and survival of cells on which it is expressed. In this review, we focus on the complex cytoplasmic domain of PECAM-1 and describe what is presently known about its structure, posttranslational modifications, and binding partners. In addition, we summarize findings that implicate PECAM-1 as an inhibitor of cellular activation via protein tyrosine kinase-dependent signaling pathways, an activator of integrins, and a suppressor of cell death via pathways that depend on damage to the mitochondria. The challenge of future research will be to bridge our understanding of the functional and biochemical properties of PECAM-1 by establishing mechanistic links between signals transduced by the PECAM-1 cytoplasmic domain and discrete cellular responses. PMID:12689916

  17. PECAM-1, apoptosis and CD34+ precursors.

    PubMed

    Zocchi, Maria R; Poggi, A

    2004-11-01

    Apoptosis is a physiological process that controls tissue homeostasis, in combination with survival signals delivered by distinct receptors that bind hormones, growth factors or extracellular matrix components. The extrinsic pathway of apoptosis is due to the triggering of death receptors and the activation of the caspase cascade; the intrinsic pathway is due to withdrawal of growth factors and mainly related to mitochondrial metabolism. The choice between survival or apoptosis, which is the result of such different integrated environmental signals, is crucial for the maintainance of bone marrow reservoir of hematopoietic precursors (HPC). CD34+ HPC can receive multiple survival signals during homing and maturation, due to different interactions with adhesion molecules expressed on endothelial and bone marrow stromal cells, proteins of the extracellular matrix and chemokines or growth factors. Among them, the signal delivered via platelet endothelial cell adhesion molecule-1 (PECAM-1) seems to contribute to the resistance of this cell population to starvation, and it is related to the maintainance of mitochondrial metabolism. Indeed, this molecule, originally described as an adhesion receptor belonging to the immunoglobulin superfamily, capable of homophilic and heterophilic interactions, turned out to be a signalling molecule, containing an immunoreceptor tyrosine-based inhibitory motifs (ITIM) within its cytoplasmic domain. In particular, it has been shown that PECAM-1 binds to different kinases and phosphatases, including the phosphatidylinositide-3-kinase that phosphorylates Akt, which, in turn can upregulate transcription and function of antiapoptotic proteins, such as Bcl-2 and Bcl-x or A1, responsible for the rescue from mitochondrial apoptosis. The possible role of PECAM-1 engagement in the prevention of starvation-induced apoptosis of HPC precursors and in the maintainance of their survival is discussed. PMID:15512808

  18. Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation.

    PubMed

    Chiu, Yi-Jen; McBeath, Elena; Fujiwara, Keigi

    2008-08-25

    Mechanosensing followed by mechanoresponses by cells is well established, but the mechanisms by which mechanical force is converted into biochemical events are poorly understood. Vascular endothelial cells (ECs) exhibit flow- and stretch-dependent responses and are widely used as a model for studying mechanotransduction in mammalian cells. Platelet EC adhesion molecule 1 (PECAM-1) is tyrosine phosphorylated when ECs are exposed to flow or when PECAM-1 is directly pulled, suggesting that it is a mechanochemical converter. We show that PECAM-1 phosphorylation occurs when detergent-extracted EC monolayers are stretched, indicating that this phosphorylation is mechanically triggered and does not require the intact plasma membrane and soluble cytoplasmic components. Using kinase inhibitors and small interfering RNAs, we identify Fyn as the PECAM-1 kinase associated with the model. We further show that stretch- and flow-induced PECAM-1 phosphorylation in intact ECs is abolished when Fyn expression is down-regulated. We suggest that PECAM-1 and Fyn are essential components of a PECAM-1-based mechanosensory complex in ECs. PMID:18710921

  19. PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets.

    PubMed

    Rathore, Vipul; Stapleton, Michelle A; Hillery, Cheryl A; Montgomery, Robert R; Nichols, Timothy C; Merricks, Elizabeth P; Newman, Debra K; Newman, Peter J

    2003-11-15

    Platelet adhesion at sites of vascular injury is mediated, in part, by interaction of the platelet plasma membrane glycoprotein (GP) Ib/V/IX complex with von Willebrand Factor (VWF) presented on collagen-exposed surfaces. Recent studies indicate that GPIb/V/IX may be functionally coupled with the Fc receptor gamma (FcR gamma)-chain, which, by virtue of its cytoplasmic immunoreceptor tyrosine-based activation motif, sends activation signals into the cell. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an inhibitory receptor that has previously been shown to negatively regulate platelet responses to collagen, which transduces activation signals via the GPVI/FcR gamma-chain complex. To determine whether PECAM-1 might similarly regulate signals emanating from GPIb/FcR gamma, we compared activation and aggregation responses to VWF of PECAM-1-positive and PECAM-1-deficient murine platelets. PECAM-1 and the FcR gamma-chain became rapidly tyrosine phosphorylated in platelets following botrocetin-induced VWF binding, but FcR gamma-chain tyrosine phosphorylation was delayed in PECAM-1-positive, versus PECAM-1-deficient, platelets. PECAM-1-deficient platelets were hyperaggregable to VWF, exhibited enhanced spreading and, under conditions of arterial flow, formed markedly larger thrombi on immobilized VWF than did wild-type platelets. Taken together, these data support the notion that engagement of the GPIb complex, in addition to sending activation signals, also initiates a negative feedback loop involving PECAM-1 that controls the rate and extent of platelet activation. PMID:12893757

  20. PECAM-1: regulator of endothelial junctional integrity.

    PubMed

    Privratsky, Jamie R; Newman, Peter J

    2014-03-01

    PECAM-1 (also known as CD31) is a cellular adhesion and signaling receptor comprising six extracellular immunoglobulin (Ig)-like homology domains, a short transmembrane domain and a 118 amino acid cytoplasmic domain that becomes serine and tyrosine phosphorylated upon cellular activation. PECAM-1 expression is restricted to blood and vascular cells. In circulating platelets and leukocytes, PECAM-1 functions largely as an inhibitory receptor that, via regulated sequential phosphorylation of its cytoplasmic domain, limits cellular activation responses. PECAM-1 is also highly expressed at endothelial cell intercellular junctions, where it functions as a mechanosensor, as a regulator of leukocyte trafficking and in the maintenance of endothelial cell junctional integrity. In this review, we will describe (1) the functional domains of PECAM-1 and how they contribute to its barrier-enhancing properties, (2) how the physical properties of PECAM-1 influence its subcellular localization and its ability to influence endothelial cell barrier function, (3) various stimuli that initiate PECAM-1 signaling and/or function at the endothelial junction and (4) cross-talk of PECAM-1 with other junctional molecules, which can influence endothelial cell function. PMID:24435645

  1. Reactive oxygen species induce reversible PECAM-1 tyrosine phosphorylation and SHP-2 binding.

    PubMed

    Maas, Matthias; Wang, Ronggang; Paddock, Cathy; Kotamraju, Srigiridhar; Kalyanaraman, Balaraman; Newman, Peter J; Newman, Debra K

    2003-12-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) functions to control the activation and survival of the cells on which it is expressed. Many of the regulatory functions of PECAM-1 are dependent on its tyrosine phosphorylation and subsequent recruitment of the Src homology (SH2) domain containing protein tyrosine phosphatase SHP-2. The recent demonstration that PECAM-1 tyrosine phosphorylation occurs in cells exposed to the reactive oxygen species hydrogen peroxide (H2O2) suggested that this form of oxidative stress may also support PECAM-1/SHP-2 complex formation. In the present study, we show that PECAM-1 tyrosine phosphorylation in response to exposure of cells to H2O2 is reversible, involves a shift in the balance between kinase and phosphatase activities, and supports binding of SHP-2 and recruitment of this phosphatase to cell-cell borders. We speculate, however, that the unique ability of H2O2 to reversibly oxidize the reactive site cysteine residues of protein tyrosine phosphatases may result in transient inactivation of the SHP-2 that is bound to PECAM-1 under these conditions. Finally, we provide evidence that PECAM-1 tyrosine phosphorylation and SHP-2 binding in endothelial cells requires exposure to an "oxidative burst" of H2O2, but that exposure of these cells to sufficiently high concentrations of H2O2 for a sufficiently long period of time abrogates binding of SHP-2 to tyrosine-phosphorylated PECAM-1. These findings support a role for PECAM-1 as a sensor of oxidative stress, perhaps most importantly during the process of inflammation. PMID:12893640

  2. PECAM-1-regulated signalling thresholds control tolerance in anergic transgenic B-cells.

    PubMed

    Wong, Mae-Xhum; Hayball, John D; Jackson, Denise E

    2008-03-01

    Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) is an immunoglobulin (Ig)-immunoreceptor tyrosine based inhibitory motif (Ig-ITIM) superfamily member that recruits and activates protein-tyrosine phosphatases, predominantly SHP-2 and to a lesser extent, SHP-1. Previously, we have shown that deletion of PECAM-1 results in a hyper-proliferative B-cell phenotype. We wanted to test whether the Ig-ITIM superfamily member, PECAM-1 maintains peripheral tolerance by regulating signalling thresholds of B-cells that control autoantibody production or relaxed negative selection of autoreactive B-cells in bone marrow. In order to address this issue, we utilised the classical model of lysozyme/immunoglobulin transgenic mouse model that defines thresholds for eliminating or inactivating self-reactive B-cells. In this study, we show that breeding of double transgenes: soluble hen egg lysozyme (HEL) and its corresponding high-affinity receptor (HEL-Ig) onto PECAM-1 null background resulted in a spontaneous loss of B-cell tolerance in vivo. The resultant PECAM-1(-/-) Dbl Tg mice displayed elevated levels of anti-HEL immunoglobulin M (IgM) antibodies in the serum compared to PECAM-1+/+ anergic counterparts. Dbl Tg B-cells lacking PECAM-1 showed enhanced B-cell proliferation and calcium flux responses to LPS, IL-4 alone, IgM cross-linking and IL-4 indicating augmentation of antigen-receptor signalling. Thus, PECAM-1 is important in maintaining peripheral tolerance in Dbl Tg B-cells. PMID:17977600

  3. Intercellular adhesion molecule-1 in the heart.

    PubMed

    Niessen, Hans W M; Krijnen, Paul A J; Visser, Cees A; Meijer, Chris J L M; Hack, C Erik

    2002-11-01

    Intercellular adhesion molecule-1 (ICAM-1) belongs to the superfamily of immunoglobulin-like adhesion molecules. Up-regulation of ICAM-1 occurs in many different pathophysiological processes. Also, cardiomyocytes can express ICAM-1-for example, in acute myocardial infarction. Moreover, inhibition of ICAM-1 expression in the heart dramatically reduces infarct size. Hence, inhibitors of ICAM-1 may provide a novel therapeutic option for acute myocardial infarction.

  4. Role of immunoreceptor tyrosine-based inhibitory motifs of PECAM-1 in PECAM-1-dependent cell migration.

    PubMed

    O'Brien, Christopher D; Cao, Gaoyuan; Makrigiannakis, Antonis; DeLisser, Horace M

    2004-10-01

    Platelet endothelial cell adhesion molecule (PECAM-1), a transmembrane glycoprotein, has been implicated in angiogenesis, with recent evidence indicating the involvement of PECAM-1 in endothelial cell motility. The cytoplasmic domain of PECAM-1 contains two tyrosine residues, Y663 and Y686, that each fall within an immunoreceptor tyrosine-based inhibitory motif (ITIM). When phosphorylated, these residues together mediate the binding of the protein tyrosine phosphatase SHP-2. Because SHP-2 has been shown to be involved in the turnover of focal adhesions, a phenomenon required for efficient cell motility, the association of this phosphatase with PECAM-1 via its ITIMs may represent a mechanism by which PECAM-1 might facilitate cell migration. Studies were therefore done with cell transfectants expressing wild-type PECAM or mutant PECAM-1 in which residues Y663 and Y686 were mutated. These mutations eliminated PECAM-1 tyrosine phosphorylation and the association of PECAM-1 with SHP-2 but did not impair the ability of the molecule to localize at intercellular junctions or to bind homophilically. However, in vitro cell motility and tube formation stimulated by the expression of wild-type PECAM-1 were abrogated by the mutation of these tyrosine residues. Importantly, during wound-induced migration, the number of focal adhesions as well as the level of tyrosine phosphorylated paxillin detected in cells expressing wild-type PECAM-1 were markedly reduced compared with control cells or transfectants with mutant PECAM-1. These data suggest that, in vivo, the binding of SHP-2 to PECAM-1, via PECAM-1's ITIM domains, promotes the turnover of focal adhesions and, hence, endothelial cell motility. PMID:15201144

  5. PECAM-1 (CD31) Expression Modulates Bleeding Time in Vivo

    PubMed Central

    Mahooti, Sepi; Graesser, Donnasue; Patil, Sonali; Newman, Peter; Duncan, Gordon; Mak, Tak; Madri, Joseph A.

    2000-01-01

    PECAM-1 is a 130-kd member of the Ig superfamily present on endothelial cells, platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes. Its expression begins early in development and persists through adulthood. PECAM-1 functions as an adhesion and signaling molecule between adjacent endothelial cells and between endothelial cells and circulating blood elements. Antibodies directed against PECAM-1 have been shown to affect angiogenesis, endothelial cell migration, and polymorphonuclear leukocyte transmigration. Furthermore, its dimerization is associated with the modulation of integrin affinity. Antibody inhibition studies suggest that PECAM-1 plays a role in modulating thrombosis; however, recent in vitro aggregation studies performed on platelets harvested from PECAM-1-deficient mice revealed no abnormalities. In this report we demonstrate prolonged in vivo bleeding times in PECAM-1-deficient mice. This abnormality was not corrected when wild-type hematopoietic precursors were engrafted into marrow-ablated PECAM-1-deficient mice. Furthermore, normal bleeding times were observed when marrow-ablated wild-type mice were engrafted with hematopoietic precursors harvested from PECAM-1-deficient mice. These studies are consistent with a role for PECAM-1 in modulating thrombosis in the vasculature, which is potentially mediated by endothelial cell PECAM-1 expression. PMID:10880378

  6. PECAM-1 gene polymorphism (rs668) and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus

    PubMed Central

    Nikolajević Starčević, J; Šantl Letonja, M; Makuc, J; Cokan Vujkovac, A; Reschner, H; Bregar, D; Petrovič, D

    2016-01-01

    ABSTRACT The platelet endothelial cell adhesion molecule 1 (PECAM-1) plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G) is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668) was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.

  7. Angiopoietins-1 and -2 play opposing roles in endothelial sprouting of embryoid bodies in 3D culture and their receptor Tie-2 associates with the cell-cell adhesion molecule PECAM1.

    PubMed

    Gu, Angel; Shively, John E

    2011-09-10

    Angiopoietins 1 and 2, ligands for the receptor kinase Tie-2, have been proposed to play critical but opposing roles in vascular development. Since signaling by Tie-2 is likely affected by other endothelial cell receptors such as Flk-1, the receptor for VEGF, and cell-cell adhesion receptors PECAM1 and VE-cad, we explored their interactions in a 3D model of vasculogenesis. When murine embryoid bodies (EBs) were treated with VEGF in Matrigel in the presence or absence of Ang-1 or Ang-2 for eight days, Ang-1 abrogated vascular sprouting for treatments started at days 0 or 3. In contrast, Ang-2 greatly accelerated vascular sprouting compared to untreated EBs. These results were confirmed in a second model system where VEGF treated HUVECs were grown in Matrigel in the presence or absence of Ang-1 or Ang-2. Since vascular sprouting must be precisely controlled in the developing embryo, it is likely that cell-cell adhesion molecules play a role in sensing the density of vascular sprouts. In this respect, we have shown that PECAM1 and CEACAM1 play essential roles in vascular sprouting. We now show that PECAM1 is associated with Tie-2, becomes phosphorylated on its ITIMs, and recruits the inhibitory phosphatases SHP-1 and SHP-2. In addition, PECAM1 is associated with VE-cad and may similarly regulate its signaling via recruitment of SHP-1/2.

  8. The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin alpha(IIb)beta3 in platelets.

    PubMed

    Wee, Janet L; Jackson, Denise E

    2005-12-01

    Previous studies have implicated the immunoglobulin (Ig)-immunoreceptor tyrosine-based inhibitory motif (ITIM) superfamily member platelet endothelial cell adhesion molecule-1 (PECAM-1) in the regulation of integrin function. While PECAM-1 has been demonstrated to play a role as an inhibitory coreceptor of immunoreceptor tyrosine-based activation motif (ITAM)-associated Fcgamma receptor IIa (FcgammaRIIa) and glycoprotein VI (GPVI)/FcR gamma-chain signaling pathways in platelets, its physiologic role in integrin alpha(IIb)beta3-mediated platelet function is unclear. In this study, we investigate the functional importance of PECAM-1 in murine platelets. Using PECAM-1-deficient mice, we show that the platelets have impaired "outside-in" integrin alpha(IIb)beta3 signaling with impaired platelet spreading on fibrinogen, failure to retract fibrin clots in vitro, and reduced tyrosine phosphorylation of focal adhesion kinase p125 (125FAK) following integrin alpha(IIb)beta3-mediated platelet aggregation. This functional integrin alpha(IIb)beta3 defect could not be attributed to altered expression of integrin alpha(IIb)beta3. PECAM-1-/- platelets displayed normal platelet alpha granule secretion, normal platelet aggregation to protease-activated receptor-4 (PAR-4), adenosine diphosphate (ADP), and calcium ionophore, and static platelet adhesion. In addition, PECAM-1-/- platelets displayed normal "inside-out" integrin alpha(IIb)beta3 signaling properties as demonstrated by normal agonist-induced binding of soluble fluoroscein isothiocyanate (FITC)-fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and inositol (1,4,5)P3 triphosphate (IP3) levels. This study provides direct evidence that PECAM-1 is essential for normal integrin alpha(IIb)beta3-mediated platelet function and that disruption of PECAM-1 induced a moderate "outsidein" integrin alpha(IIb)beta3 signaling defect. PMID:16081692

  9. The human PECAM1 gene maps to 17q23

    SciTech Connect

    Gumina, R.J.; Rao, P.N.; Tuinen, P. van

    1996-06-01

    We have determined the chromosomal and regional location of the gene encoding PECAM-1 (termed PECAM1 by GBI) nomenclature using a polymerase chain reaction (PCR)-based analysis of somatic cell hybrids. Analysis of a somatic cell hybrid chromosome panel established that the PECAM1 gene is on chromosome 17. Interestingly, several adhesion molecules expressed on platelets and endothelium also localize to chromosome 17: the GP1BA locus (glycoprotein (GP) Ib{alpha}) has been provisionally mapped to the region 17p12-pter, the ITGA2b (GPIIb) and the ITGB3 (GPI-IIa) loci have been confirmed to the region 17q21.32; and the ICAM2 locus has been provisionally mapped to the region 17q23-q25. To determine if the PECAM1 locus colocalizes with any of the loci for these adhesion molecules, PCR-based analysis of a regional mapping panel for human chromosome 17 was conducted. We found that the PECAM1 locus is on the long arm of chromosome 17, i the region q23-qter. To confirm this observation and obtain a more precise localization of the PECAM1 locus, fluorescence in situ hybridization was conducted. Together our data allowed assignment of the PECAM1 locus to the region 17q23. 18 refs., 2 figs.

  10. Identification of PECAM-1 association with sphingosine kinase 1 and its regulation by agonist-induced phosphorylation.

    PubMed

    Fukuda, Yu; Aoyama, Yuki; Wada, Atsushi; Igarashi, Yasuyuki

    2004-02-27

    Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated from sphingosine by sphingosine kinase (SPHK). S1P acts both extracellularly and intracellularly as a signaling molecule, although its intracellular targets are still undefined. Intracellular level of S1P is under strict regulatory control of SPHK regulation, S1P degradation, and S1P dephosphorylation. Therefore, clarifying the mechanisms regulating SPHK activity may help us understand when and where S1P is generated. In this study, we performed yeast two-hybrid screening to search for SPHK1a-binding molecules that may be involved in the regulation of the kinase localization or activity. Platelet endothelial cell adhesion molecule-1 (PECAM-1) was identified as a protein potentially associating with SPHK1a. Their association was confirmed by co-immunoprecipitation analysis using HEK293 cells overexpressing PECAM-1 and SPHK1a. Moreover, the kinase activity appeared to be reduced in stable PECAM-1-expressing cells. PECAM-1 is expressed on the cell surface of vascular cells, and several stimuli are known to induce phosphorylation of its tyrosine residues. We found that such phosphorylation attenuated its association with SPHK1a. This association/dissociation of SPHK with PECAM-1, regulated by the phosphorylated state of the membrane protein, may be involved in the control of localized kinase activity in certain cell types. PMID:14984734

  11. The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

    PubMed Central

    Shi, Jing; Hu, Chun-lin; Gao, Yu-feng; Liao, Xiao-xing; Xu, Hope

    2012-01-01

    BACKGROUND: Platelet endothelial cell adhesion molecule-1 (PECAM-1), also known as CD31, is mainly distributed in vascular endothelial cells. Studies have shown that PECAM-1 is a very significant indicator of angiogenesis, and has been used as an indicator for vascular endothelial cells. The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury (ALI) and fibrosis in paraquat (PQ) induced lung injury in rabbits. METHODS: Thirty-six adult New Zealand rabbits were randomly divided into three groups (12 rabbits in each group) according to PQ dosage: 8 mg/kg (group A), 16 mg/kg (group B), and 32 mg/kg (group C). After PQ infusion, the rabbits were monitored for 7 days and then euthanized. The lungs were removed for histological evaluation. Masson staining was used to determine the degree of lung fibrosis (LF), and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1. Pearson’s product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF. RESULTS: Rabbits in the three groups showed apparent poisoning. The rabbits survived longer in group A than in groups B and C (6.47±0.99 days vs. 6.09±1.04 days vs. 4.77±2.04 days) (P<0.05). ALI score was lower in group A than in groups B and C (8.33±1.03 vs. 9.83±1.17 vs. 11.50±1.38) (P<0.05), and there was statistically significant difference between group B and group C (P=0.03). LF was slighter in group A than in groups B and C (31.09%±2.05 % vs. 34.37%±1.62 % vs. 36.54%±0.44%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.026). The PEACAM-1 expression was higher in group A than in groups B and C (20.31%±0.70% vs. 19.34%±0.68% vs. 18.37%±0.46%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.017). Pearson

  12. PECAM-1: a multifaceted regulator of megakaryocytopoiesis

    PubMed Central

    Wu, Yue; Welte, Thomas; Michaud, Michael

    2007-01-01

    PECAM-1 (CD31) knockout (KO) mice exhibit excessive megakaryocytopoiesis accompanied by increased numbers of megakaryocytes associated with the stromal niche rather than the vascular niche. During earlier stages of megakaryocytopoiesis in KO marrow, an expanded Lin−Sca-1+ c-kit+ hematopoietic stem cell (HSC) population and increased quiescent Lin− progenitor pool were identified. During the later stages of megakaryocytopoiesis, CD31KO megakaryocytes exhibited abnormal adhesion/transmigration behaviors. Lastly, KO animals exhibited excessive splenic extramedullary megakaryocytopoiesis, which likely compensates for the impaired marrow megakaryocytopoiesis, resulting in normal peripheral platelet number. Thus, PECAM-1 modulates megakaryocytopoiesis in a hierarchic manner, functioning as a thermostat to “fine-tune” megakaryocytopoiesis. PMID:17412889

  13. Effect of aqueous tobacco smoke extract and shear stress on PECAM-1 expression and cell motility in human uterine endothelial cells.

    PubMed

    Soghomonians, Arlen; Thirkill, Twanda L; Mariano, Natalie F; Barakat, Abdul I; Douglas, Gordon C

    2004-10-01

    Tobacco smoke constituents have several adverse effects on endothelial cells. Exposure to tobacco smoke during pregnancy is associated with adverse effects on pregnancy outcome possibly related to endothelial dysfunction. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an important regulator of endothelial function. This study tests the idea that an aqueous extract of cigarette smoke alters the expression of PECAM-1 in uterine endothelial cells. Human uterine microvascular endothelial cells were cultured in cigarette smoke-conditioned medium (CSM) under arterial physiological flow conditions (shear or frictional stress in the range 7.5-15 dyne/cm(2)) and the expression of PECAM-1 was assessed by immunofluorescence microscopy and Western blotting. Thick reticular PECAM-1-associated bands found at cell-cell junctions in static cultures became significantly thinner or disappeared when the cells were exposed to shear stress or to CSM for 24 h. This diminution at cell junctions was accompanied by increased punctate cytoplasmic/cell surface staining. Under shear stress conditions, PECAM-1 was equally distributed between cell surface and intracellular sites. In contrast, when cells were exposed to both shear stress and CSM, PECAM-1 was predominantly localized to the cell surface. It was shown that shear stress increased endothelial cell migration and that CSM abrogated this effect. These results suggest that, under shear stress conditions, PECAM-1 is not predominantly concentrated at intercellular junctions in uterine endothelial cells. Exposure of cells to unidentified soluble components of cigarette smoke leads to alterations in PECAM-1 distribution that may cause endothelial dysfunction. If this occurs in vivo it could contribute to the adverse effects on pregnancy outcome associated with exposure to cigarette smoke.

  14. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells.

    PubMed

    Fleming, Ingrid; Fisslthaler, Beate; Dixit, Madhulika; Busse, Rudi

    2005-09-15

    The application of fluid shear stress to endothelial cells elicits the formation of nitric oxide (NO) and phosphorylation of the endothelial NO synthase (eNOS). Shear stress also elicits the enhanced tyrosine phosphorylation of endothelial proteins, especially of those situated in the vicinity of cell-cell contacts. Since a major constituent of these endothelial cell-cell contacts is the platelet endothelial cell adhesion molecule-1 (PECAM-1) we assessed the role of PECAM-1 in the activation of eNOS. In human endothelial cells, shear stress induced the tyrosine phosphorylation of PECAM-1 and enhanced the association of PECAM-1 with eNOS. Endothelial cell stimulation with shear stress elicited the phosphorylation of Akt and eNOS as well as of the AMP-activated protein kinase (AMPK). While the shear-stress-induced tyrosine phosphorylation of PECAM-1 as well as the serine phosphorylation of Akt and eNOS were abolished by the pre-treatment of cells with the tyrosine kinase inhibitor PP1 the phosphorylation of AMPK was unaffected. Down-regulation of PECAM-1 using a siRNA approach attenuated the shear-stress-induced phosphorylation of Akt and eNOS, as well as the shear-stress-induced accumulation of cyclic GMP levels while the shear-stress-induced phosphorylation of AMPK remained intact. A comparable attenuation of Akt and eNOS (but not AMPK) phosphorylation and NO production was also observed in endothelial cells generated from PECAM-1-deficient mice. These data indicate that the shear-stress-induced activation of Akt and eNOS in endothelial cells is modulated by the tyrosine phosphorylation of PECAM-1 whereas the shear-stress-induced phosphorylation of AMPK is controlled by an alternative signaling pathway. PMID:16118242

  15. PECAM-1 and caveolae form the mechanosensing complex necessary for NOX2 activation and angiogenic signaling with stopped flow in pulmonary endothelium

    PubMed Central

    Noel, John; Wang, Hui; Hong, Nankang; Tao, Jian-Qin; Yu, Kevin; Sorokina, Elena M.; DeBolt, Kristine; Heayn, Michelle; Rizzo, Victor; Delisser, Horace; Fisher, Aron B.

    2013-01-01

    We showed that stop of flow triggers a mechanosignaling cascade that leads to the generation of reactive oxygen species (ROS); however, a mechanosensor coupled to the cytoskeleton that could potentially transduce flow stimulus has not been identified. We showed a role for KATP channel, caveolae (caveolin-1), and NADPH oxidase 2 (NOX2) in ROS production with stop of flow. Based on reports of a mechanosensory complex that includes platelet endothelial cell adhesion molecule-1 (PECAM-1) and initiates signaling with mechanical force, we hypothesized that PECAM-1 could serve as a mechanosensor in sensing disruption of flow. Using lungs in situ, we observed that ROS production with stop of flow was significantly reduced in PECAM-1−/− lungs compared with lungs from wild-type (WT) mice. Lack of PECAM-1 did not affect NOX2 activation machinery or the caveolin-1 expression or caveolae number in the pulmonary endothelium. Stop of flow in vitro triggered an increase in angiogenic potential of WT pulmonary microvascular endothelial cells (PMVEC) but not of PECAM-1−/− PMVEC. Obstruction of flow in lungs in vivo showed that the neutrophil infiltration as observed in WT mice was significantly lowered in PECAM-1−/− mice. With stop of flow, WT lungs showed higher expression of the angiogenic marker VEGF compared with untreated (sham) and PECAM-1−/− lungs. Thus PECAM-1 (and caveolae) are parts of the mechanosensing machinery that generates superoxide with loss of shear; the resultant ROS potentially drives neutrophil influx and acts as an angiogenic signal. PMID:24077950

  16. RhoA activation and actin reorganization involved in endothelial CAM-mediated endocytosis of anti-PECAM carriers: critical role for tyrosine 686 in the cytoplasmic tail of PECAM-1.

    PubMed

    Garnacho, Carmen; Shuvaev, Vladimir; Thomas, Anu; McKenna, Lindsay; Sun, Jing; Koval, Michael; Albelda, Steven; Muzykantov, Vladimir; Muro, Silvia

    2008-03-15

    Platelet-endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane glycoprotein involved in leukocyte transmigration, represents a good target for endothelial drug delivery (eg, using antibody-directed nanocarriers, anti-PECAM/NCs). Although endothelial cells do not internalize PECAM antibodies, PECAM-1 engagement by multivalent anti-PECAM conjugates and nanocarriers causes endocytosis via a nonclassic CAM-mediated pathway. We found that endothelial uptake of multivalent anti-PECAM complexes is associated with PECAM-1 phosphorylation. Using model REN cells expressing a series of PECAM-1 deletion and point mutants, we found that the PECAM-1 cytoplasmic domain and, more precisely, PECAM-1 tyrosine 686, is critical in mediating RhoA activation and recruitment of EGFP-RhoA to anti-PECAM/NC binding sites at the plasmalemma, actin polymerization into phalloidin-positive stress fibers, and finally CAM endocytosis of anti-PECAM/NCs. Endothelial targeting and endocytosis of anti-PECAM/NCs were markedly efficient and did not compromise endothelial barrier function in vitro (determined by immunostaining of VE-cadherin and (125)I-albumin transport across endothelial monolayers) or in vivo (determined by electron microscopy imaging of pulmonary capillaries and (125)I-albumin transport from the blood into the lung tissue after intravenous injection of anti-PECAM/NCs in mice). These results reveal PECAM-1 signaling and interactions with the cytoskeleton, which are required for CAM-endocytosis, and may provide safe intra-endothelial drug delivery by anti-PECAM/NCs. PMID:18182571

  17. Insights into monocyte-driven osteoclastogenesis and its link with hematopoiesis: regulatory roles of PECAM-1 (CD31) and SHP-1.

    PubMed

    Wu, Yue; Madri, Joseph

    2010-01-01

    Osteoclasts are derived from hematopoietic cells of monocyte-macrophage lineage. Osteoclastogenesis is orchestrated by the migration of monocytic osteoclast progenitor cells in close proximity to bone surfaces destined for resorption. Although the overall roles of monocyte migratory behavior in osteoclastogenesis remain enigmatic, impaired monocyte migration can lead to either decreased or increased osteoclastogenesis, which appears contingent upon the roles of migration in either fusion events required for osteoclast formation or terminal differentiation of osteoclasts. The cell adhesion molecule PECAM-1 (platelet endothelial cell adhesion molecule 1), in concert with the tyrosine phosphatase SHP-1 (Src homology 2-containing protein tyrosine phosphatase 1) and tyrosine kinase Syk-1 (spleen tyrosine kinase 1), functions as a negative regulator of osteoclastogenesis. Both PECAM-1 (CD31) and SHP-1 knockout mice exhibit not only increased osteoclastogenesis but also abnormal hematopoiesis, which is suggestive of the intricate interplay between hematopoiesis and osteoclastogenesis. Interestingly, the most pronounced effect of PECAM-1 deficiency on hematopoiesis is reflected by excessive megakaryocytopoiesis. Emerging data have suggested the role of megakaryocytes in bone remodeling. Megakaryocytopoiesis-osteoclastogenesis interactions are discussed herein, reconciling the discrepancies shown by different studies in this area. PECAM-1 and non-receptor tyrosine phosphatase polymorphisms have been revealed in a spectrum of diseases. The complex regulatory roles of PECAM-1 and SHP-1 in vivo suggest the potential utilization of polymorphisms of these genes for diagnostic purposes. PMID:21083524

  18. Breakdown of paraendothelial barrier function during Marburg virus infection is associated with early tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1.

    PubMed

    Böckeler, Michael; Ströher, Ute; Seebach, Jochen; Afanasieva, Tatiana; Suttorp, Norbert; Feldmann, Heinz; Schnittler, Hans-Joachim

    2007-11-15

    Marburg virus (MARV) infection often causes fulminant shock due to pathologic immune responses and alterations of the vascular system. Cytokines released from virus-infected monocytes/macrophages provoke endothelial activation and vascular hyperpermeability and contribute to the development of shock. Tyrosine phosphorylation of cell-junction proteins is important for the regulation of paraendothelial barrier function. We showed that mediators released from MARV-infected monocytes/macrophages, as well as recombinant tumor necrosis factor (TNF)- alpha /H2O2 and interferon (IFN)- gamma , caused tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1) but not of the vascular endothelial (VE) cadherin/catenin complex proteins. Tyrosine phosphorylation of PECAM-1 was associated with delayed opening of interendothelial junctions. Interestingly, we observed an early increase in water permeability in response to TNF- alpha /H2O2 that was not due to an opening of the interendothelial junctions. These data indicate 2 distinct mechanisms for the TNF- alpha /H2O2-mediated decrease in endothelial barrier function involving tyrosine phosphorylation of PECAM-1 but not requiring tyrosine phosphorylation of VE-cadherin or catenin proteins. PMID:17940969

  19. Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation.

    PubMed

    Udell, Christian M; Samayawardhena, Lionel A; Kawakami, Yuko; Kawakami, Toshiaki; Craig, Andrew W B

    2006-07-28

    Mast cells express the high affinity IgE receptor FcepsilonRI, which upon aggregation by multivalent antigens elicits signals that cause rapid changes within the mast cell and in the surrounding tissue. We previously showed that FcepsilonRI aggregation caused a rapid increase in phosphorylation of both Fer and Fps/Fes kinases in bone marrow-derived mast cells. In this study, we report that FcepsilonRI aggregation leads to increased Fer/Fps kinase activities and that Fer phosphorylation downstream of FcepsilonRI is independent of Syk, Fyn, and Gab2 but requires Lyn. Activated Fer/Fps readily phosphorylate the C terminus of platelet-endothelial cell adhesion molecule 1 (Pecam-1) on immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and a non-ITIM residue (Tyr(700)) in vitro and in transfected cells. Mast cells devoid of Fer/Fps kinase activities display a reduction in FcepsilonRI aggregation-induced tyrosine phosphorylation of Pecam-1, with no defects in recruitment of Shp1/Shp2 phosphatases observed. Lyn-deficient mast cells display a dramatic reduction in Pecam-1 phosphorylation at Tyr(685) and a complete loss of Shp2 recruitment, suggesting a role as an initiator kinase for Pecam-1. Consistent with previous studies of Pecam-1-deficient mast cells, we observe an exaggerated degranulation response in mast cells lacking Fer/Fps kinases at low antigen dosages. Thus, Lyn and Fer/Fps kinases cooperate to phosphorylate Pecam-1 and activate Shp1/Shp2 phosphatases that function in part to limit mast cell activation. PMID:16731527

  20. Evidence for the involvement of PECAM-1 in a receptor mediated signal-transduction pathway regulating capacitation-associated tyrosine phosphorylation in human spermatozoa.

    PubMed

    Nixon, Brett; Paul, Jonathan W; Spiller, Cassy M; Attwell-Heap, Abigail G; Ashman, Leonie K; Aitken, R John

    2005-10-15

    Mammalian spermatozoa must become ;capacitated' in the female reproductive tract before they gain the ability to fertilize the oocyte. The attainment of a capacitated state has been correlated with a number of biochemical changes, the most notable of which is a dramatic increase in the tyrosine phosphorylation status of these cells. Despite its biological importance, the mechanisms responsible for initiating this tyrosine phosphorylation cascade in vivo are unknown. Here, we report that this signalling pathway can be elicited in a rapid, dose-dependent and lectin-specific manner by wheat germ agglutinin (WGA), but none of 18 other lectins assessed. This response was abrogated by prior enzymatic cleavage of either sialic acid or GlcNAc residues from the sperm surface and by treatment with a range of pharmacological inhibitors directed against protein kinase A, protein tyrosine kinases and intermediates including Src. Proteomic analysis of the WGA-binding sites on the sperm surface identified the putative cognate receptor as platelet cell adhesion molecule 1 (PECAM-1/CD31). This conclusion was supported by the following evidence: (i) anti-PECAM-1 antibodies identified a molecule of the correct molecular mass in human spermatozoa, (ii) PECAM-1 could be isolated from a pool of sperm surface proteins using WGA immobilized on a solid phase support, (iii) PECAM-1 and WGA co-localized to the sperm surface and (iv) anti-PECAM-1 antibodies could completely block the ability of WGA to stimulate tyrosine phosphorylation in these cells. Collectively, these data provide the first evidence that a receptor-mediated signal transduction pathway triggers human sperm capacitation and identifies PECAM-1 as the probable initiator of this second messenger cascade. PMID:16219692

  1. CD44 regulates vascular endothelial barrier integrity via a PECAM-1 dependent mechanism.

    PubMed

    Flynn, Kelly M; Michaud, Michael; Canosa, Sandra; Madri, Joseph A

    2013-07-01

    Vascular integrity is a critical parameter in normal growth and development. Loss of appropriate vascular barrier function is present in various immune- and injury-mediated pathological conditions. CD44 is an adhesion molecule expressed by multiple cell types, including endothelial cells (EC). The goal of the present study was to examine how loss of CD44 affected vascular permeability. Using C57BL/6 WT and CD44-KO mice, we found no significant permeability to Evan's Blue in either strain at baseline. However, there was significantly increased histamine-induced permeability in CD44-deficient mice compared to WT counterparts. Similar results were observed in vitro, where CD44-deficient endothelial monolayers were also impermeable to 40kD-FITC dextran in the absence of vasoactive challenge, but exhibited enhanced and prolonged permeability following histamine. However, CD44-KO monolayers have reduced baseline barrier strength by electrical resistance, which correlated with increased permeability, at baseline, to smaller molecular weight 4-kD FITC-dextran, suggesting weakly formed endothelial junctions. The CD44-KO EC displayed several characteristics consistent with impaired barrier function/dysfunctional EC junctions, including differential expression, phosphorylation, and localization of endothelial junction proteins, increased matrix metalloprotease expression, and altered cellular morphology. Reduced platelet endothelial cell adhesion molecule-1 (PECAM-1) expression by CD44-KO EC in vivo and in vitro was also observed. Reconstitution of murine CD44 or PECAM-1 restored these defects to near WT status, suggesting CD44 regulates vascular permeability and integrity through a PECAM-1 dependent mechanism.

  2. Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

    PubMed

    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. PMID:20194726

  3. Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology.

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-06-01

    Platelet endothelial cell adhesion molecule (PECAM-1) is highly expressed in vascular cells such as endothelial cells (ECs) and blood-borne cells like platelets and leukocytes. In ECs, this molecule controls junctional and adhesive properties. In physiological conditions, PECAM-1 supports the endothelial barrier function. In inflammation that is observed in vessels affected by atherosclerosis, the function of PECAM-1 is impaired, an event that leads to increased adhesion of neutrophils and other leukocytes to ECs, decreased vascular integrity, and higher leukocyte transmigration to the intima media. PECAM-1 has six extracellular immunoglobulin (Ig)-like domains that support attraction and adhesion of leukocytes to ECs. The cytoplasmic tail of PECAM-1 contains two tyrosine residues (Tyr-663 and Tyr-686) that could be phosphorylated by Src family protein kinases is involved in the intracellular signaling. Actually, those tyrosines are the part of the immunoreceptor tyrosine-based inhibition motifs (ITIMs) that inhibit inflammation. However, in atherosclerosis, the PECAM-1-dependent immune suppression is disturbed. This in turn facilitates recruitment of leukocytes and supports proatherogenic inflammation. PMID:27079772

  4. MAPKs (ERK1/2, p38) and AKT can be phosphorylated by shear stress independently of platelet endothelial cell adhesion molecule-1 (CD31) in vascular endothelial cells.

    PubMed

    Sumpio, Bauer E; Yun, Sangseob; Cordova, Alfredo C; Haga, Masae; Zhang, Jin; Koh, Yongbok; Madri, Joseph A

    2005-03-25

    PECAM-1 (CD31) is a member of the Ig superfamily of cell adhesion molecules and is expressed on endothelial cells (EC) as several circulating blood elements including platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes. PECAM-1 tyrosine phosphorylation has been observed following mechanical stimulation of EC but its role in mechanosensing is still incompletely understood. The aim of this study was to investigate the involvement of PECAM-1 in signaling cascades in response to fluid shear stress (SS) in vascular ECs. PECAM-1-deficient (KO) and PECAM-reconstituted murine microvascular ECs, 50 and 100% confluent bovine aortic EC (BAEC), and human umbilical vein EC (HUVEC) transfected with antisense PECAM-1 oligonucleotides were exposed to oscillatory SS (14 dynes/cm2) for 0, 5, 10, 30 or 60 min. The tyrosine phosphorylation level of PECAM-1 immunoprecipitated from SS-stimulated PECAM-reconstituted, but not PECAM-1-KO, murine ECs increased. Although PECAM-1 was phosphorylated in 100% confluent BAEC and HUVEC, its phosphorylation level in 50% confluent BAECs or HUVEC was not detected by SS. Likewise PECAM-1 phosphorylation was robust in the wild type and scrambled-transfected HUVEC but not in the PECAM-1 antisense-HUVEC. ERK(1/2), p38 MAPK, and AKT were activated by SS in all cell types tested, including the PECAM-1-KO murine ECs, 50% confluent BAECs, and HUVEC transfected with antisense PECAM-1. This suggests that PECAM-1 may not function as a major mechanoreceptor for activation of MAPK and AKT in ECs and that there are likely to be other mechanoreceptors in ECs functioning to detect shear stress and trigger intercellular signals. PMID:15668248

  5. Carbohydrate ligands for endothelial - Leukocyte adhesion molecule 1

    SciTech Connect

    Tiemeyer, M.; Swiedler, S.J.; Ishihara, Masayuki; Moreland, M.; Schweingruber, H.; Hirtzer, P.; Brandley, B.K. )

    1991-02-15

    The acute inflammatory response requires that circulating leukocytes bind to and penetrate the vascular wall to access the site of injury. Several receptors have been implicated in this interaction, including a family of putative carbohydrate-binding proteins. The authors report here the identification of an endogenous carbohydrate ligand for one of these receptors, endothelial-leukocyte adhesion molecule 1 (ELAM-1). Radiolabeled COS cells transfected with a plasmid containing the cDNA for ELAM-1 were used as probes to screen glycolipids extracted from human leukocytes. COS cells transfected with this plasmid adhered to a subset of sialylated glycolipids resolved on TLC plates or adsorbed on polyvinyl chloride microtiter wells. Adhesion to these glycolipids required calcium but was not inhibited by heparin, chondroitin sulfate, keratan sulfate, or yeast phosphomannan. Monosaccharide composition, linkage analysis, and fast atom bombardment mass spectrometry of the glycolipids indicate that the ligands for ELAM-1 are terminally sialylated lactosylceramides with a variable number of N-acetyllactosamine repeats and at least one fucosylated N-acetylglucosamine residue.

  6. Peroxynitrite reduces the endothelium-derived hyperpolarizing factor component of coronary flow-mediated dilation in PECAM-1-knockout mice.

    PubMed

    Liu, Yanping; Bubolz, Aaron H; Shi, Yang; Newman, Peter J; Newman, Debra K; Gutterman, David D

    2006-01-01

    Platelet endothelial cell adhesion molecule 1 (PECAM-1) is capable of transducing signals in endothelial cells exposed to shear; however, the biological consequences of this signal transduction are unknown. Because shear stress elicits flow-mediated dilation (FMD), we examined whether steady-state FMD in mouse coronary arteries (MCAs) is affected in the PECAM-1 knockout (KO) mouse. MCAs were isolated from wild-type (WT) or KO mice and prepared for videomicroscopy, histofluorescence, Western blotting, and immunohistochemistry. FMD was examined in the absence and presence of N(omega)-nitro-l-arginine methyl ester (l-NAME) and l-NAME+indomethacin (INDO). FMD was reduced in KO relative to WT MCAs, but the l-NAME-inhibitable portion of FMD was similar between the two. The INDO-sensitive component of FMD was diminished in KO MCAs. In contrast, the residual component of dilation, presumably because of endothelium-derived hyperpolarizing factor (EDHF), was abolished in KO MCAs. Histofluorescence showed relatively more superoxide (O2-.; oxy-ethidium fluorescence) and peroxide production (dihydrochlorofluorescene fluoresecence) in KO MCAs at rest. Flow augmented O2-. and peroxide production in WT MCAs but had little effect on KO MCAs. Enhanced nitric oxide generation was observed in arteries from KO mice, accompanied with increased eNOS S1177 phosphorylation. In vessels from KO mice, treatment with ebselen decreased peroxynitrite (ONOO-) formation and improved the reduced FMD, largely due to restoration of the presumed EDHF component. These results suggest that PECAM-1 is necessary for normal FMD in the mouse coronary circulation. In the absence of this adhesion and signaling molecule, ONOO- production is increased concomitant with a reduction in both the EDHF and INDO-sensitive components of FMD. PMID:16166207

  7. Intercellular adhesion molecule 1 is the major adhesion molecule expressed during schistosome granuloma formation.

    PubMed Central

    Ritter, D M; McKerrow, J H

    1996-01-01

    Endothelial cell adhesion molecules play a key role in inflammation by initiating leukocyte trafficking. One of the most complex inflammatory responses is the formation of a cellular granuloma. Expression of adhesion molecules during granuloma formation was investigated by using the murine host reaction to schistosome parasite eggs deposited in the liver as a model. By both immunohistochemistry and lymphocyte adhesion assays, the predominant interaction identified was between intercellular adhesion molecule 1 (ICAM-1) and its cognate integrin, leukocyte functional antigen 1 (LFA-1). ICAM-1 expression on sinusoidal endothelium was induced when eggs were first deposited in the liver, peaked in parallel with granuloma size, and was downregulated with modulation of the granuloma. Polyacrylamide beads coated with soluble parasite egg antigens could induce ICAM-1 expression on endothelial cells in vitro only in the presence of tumor necrosis factor alpha, a cytokine previously shown to be key to granuloma formation. A role for ICAM-1 in recruiting lymphocytes to the hepatic granuloma was also supported by the observation that lymphocytes preincubated with anti-LFA-1 antibody did not bind to granulomas in tissue sections. While ICAM-1 is the predominant adhesion molecule in schistosome egg granuloma formation in wild-type mice, when the ICAM-1 gene is knocked out, vascular cell adhesion molecule 1 is upregulated and granuloma formation is preserved. PMID:8890229

  8. PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells.

    PubMed

    Couty, Jean-Pierre; Rampon, Christine; Leveque, Mathilde; Laran-Chich, Marie-Pierre; Bourdoulous, Sandrine; Greenwood, John; Couraud, Pierre-Olivier

    2007-10-01

    Interactions between leukocytes and vascular endothelial cells are mediated by a complex set of membrane adhesion molecules which transduce bi-directional signals in both cell types. Endothelium of the cerebral blood vessels, which constitute the blood-brain barrier, strictly controls adhesion and trafficking of leukocytes into the brain. Investigating signaling pathways triggered by the engagement of adhesion molecules expressed on brain endothelial cells, we previously documented the role of ICAM-1 in activation of the tyrosine phosphorylation of several actin-binding proteins and subsequent rearrangements of the actin cytoskeleton. In the present study, we show that, whereas PECAM-1 is known to control positively the trans-endothelial migration of leukocytes via homophilic interactions between leukocytes and endothelial cells, PECAM-1 engagement on brain endothelial surface unexpectedly counteracts the ICAM-1-induced tyrosine phosphorylation of cortactin and rearrangements of the actin cytoskeleton. We present evidence that the PECAM-1-associated tyrosine phosphatase SHP-2 is required for ICAM-1 signaling, suggesting that its activity might crucially contribute to the regulation of ICAM-1 signaling by PECAM-1. Our findings reveal a novel activity for PECAM-1 which, by counteracting ICAM-1-induced activation, could directly contribute to limit activation and maintain integrity of brain vascular endothelium. PMID:17662049

  9. The use of the soluble adhesion molecules sE-selectin, sICAM-1, sVCAM-1, sPECAM-1 and their ligands CD11a and CD49d as diagnostic and prognostic biomarkers in septic and critically ill non-septic ICU patients.

    PubMed

    Kjaergaard, Anders G; Dige, Anders; Nielsen, Jeppe S; Tønnesen, Else; Krog, Jan

    2016-10-01

    Endothelial activation is pivotal in the development and escalation of sepsis. Central to endothelial activation is the endothelial up-regulation of cellular adhesion molecules (CAMs) including E-selectin, ICAM-1, VCAM-1, and PECAM-1. Shed CAMs are also found in circulating soluble forms (sCAMs). We investigated whether sCAMs can be used as biomarkers for the differentiation between septic and non-septic patients. Furthermore, we investigated lymphocyte and monocyte expression of LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) ligands for ICAM-1 and VCAM-1, respectively. Twenty-one septic and 15 critically ill non-septic patients were included. All patients had an APACHE II score above 13 at ICU admission. Fifteen healthy volunteers served as controls. Flow cytometry was used to estimate levels of sE-selectin, sICAM-1, sVCAM-1, sPECAM-1, and the cellular expression of CD11a and CD49d. Levels of sE-selectin, sICAM-1 and sPECAM-1 were higher in the septic patients compared with the non-septic patients and controls at admission and during the observation period. Lymphocyte and monocyte expression of CD11a and CD49d was suppressed or unaltered in the septic patients compared with the non-septic patients and controls. Levels of sE-selectin, sICAM-1, and sPECAM-1 were able to discriminate between septic and non-septic patients, indicating that sCAMs may be potential diagnostic biomarkers of sepsis.

  10. The use of the soluble adhesion molecules sE-selectin, sICAM-1, sVCAM-1, sPECAM-1 and their ligands CD11a and CD49d as diagnostic and prognostic biomarkers in septic and critically ill non-septic ICU patients.

    PubMed

    Kjaergaard, Anders G; Dige, Anders; Nielsen, Jeppe S; Tønnesen, Else; Krog, Jan

    2016-10-01

    Endothelial activation is pivotal in the development and escalation of sepsis. Central to endothelial activation is the endothelial up-regulation of cellular adhesion molecules (CAMs) including E-selectin, ICAM-1, VCAM-1, and PECAM-1. Shed CAMs are also found in circulating soluble forms (sCAMs). We investigated whether sCAMs can be used as biomarkers for the differentiation between septic and non-septic patients. Furthermore, we investigated lymphocyte and monocyte expression of LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) ligands for ICAM-1 and VCAM-1, respectively. Twenty-one septic and 15 critically ill non-septic patients were included. All patients had an APACHE II score above 13 at ICU admission. Fifteen healthy volunteers served as controls. Flow cytometry was used to estimate levels of sE-selectin, sICAM-1, sVCAM-1, sPECAM-1, and the cellular expression of CD11a and CD49d. Levels of sE-selectin, sICAM-1 and sPECAM-1 were higher in the septic patients compared with the non-septic patients and controls at admission and during the observation period. Lymphocyte and monocyte expression of CD11a and CD49d was suppressed or unaltered in the septic patients compared with the non-septic patients and controls. Levels of sE-selectin, sICAM-1, and sPECAM-1 were able to discriminate between septic and non-septic patients, indicating that sCAMs may be potential diagnostic biomarkers of sepsis. PMID:27539881

  11. Immunoreceptor tyrosine-based inhibitory motif (ITIM)-mediated inhibitory signaling is regulated by sequential phosphorylation mediated by distinct nonreceptor tyrosine kinases: a case study involving PECAM-1.

    PubMed

    Tourdot, Benjamin E; Brenner, Michelle K; Keough, Kathleen C; Holyst, Trudy; Newman, Peter J; Newman, Debra K

    2013-04-16

    The activation state of many blood and vascular cells is tightly controlled by a delicate balance between receptors that contain immunoreceptor tyrosine-based activation motifs (ITAMs) and those that contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Precisely how the timing of cellular activation by ITAM-coupled receptors is regulated by ITIM-containing receptors is, however, poorly understood. Using platelet endothelial cell adhesion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of inhibitory signaling occurs via a novel, sequential process in which Src family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homology 2 domain-containing nonreceptor tyrosine kinases (NRTKs). NRTKs capable of mediating the second phosphorylation event include C-terminal Src kinase (Csk) and Bruton's tyrosine kinase (Btk). Btk and Csk function downstream of phosphatidylinositol 3-kinase (PI3K) activation during ITAM-dependent platelet activation. In ITAM-activated platelets that were treated with a PI3K inhibitor, PECAM-1 was phosphorylated but did not bind the tandem SH2 domain-containing tyrosine phosphatase SHP-2, indicating that it was not phosphorylated on its N-terminal ITIM. Csk bound to and phosphorylated PECAM-1 more efficiently than did Btk and required its SH2 domain to perform these functions. Additionally, the phosphorylation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phosphorylation of its C-terminal ITIM, providing evidence that the ITIMs of other dual ITIM-containing receptors are also sequentially phosphorylated. On the basis of these findings, we propose that sequential ITIM phosphorylation provides a general mechanism for precise temporal control over the recruitment and activation of tandem SH2 domain-containing tyrosine phosphatases that dampen ITAM-dependent signals. PMID:23418871

  12. Syk protein tyrosine kinase involves PECAM-1 signaling through tandem immunotyrosine inhibitory motifs in human THP-1 macrophages.

    PubMed

    Wang, Junchen; Wu, Yanling; Hu, Hai; Wang, Weimin; Lu, Ying; Mao, Huiming; Liu, Xiaoqing; Liu, Zhongmin; Chen, Bing-guan

    2011-01-01

    Although recent evidence supports a functional relationship between platelet endothelial cell adhesion molecule (PECAM-1) and Syk tyrosine kinase, little is known about the interaction of Syk with PECAM-1. We report that down-regulation of Syk inhibits the spreading of human THP-1 macrophage cells. Moreover, our data indicate that Syk binds PECAM-1 through its immune tyrosine-based inhibitory motif (ITIM), and dual phosphorylation of the ITIM domain of PECAM-1 leads to activation of Syk. Our results indicate that the distance between the phosphotyrosines could be up to 22 amino acids in length, depending on the conformational flexibility, and that the dual ITIM tyrosine motifs of PECAM-1 facilitate immunoreceptor tyrosine-based activation motif-like signaling. The preferential binding of PECAM-1 to Src homology region 2 domain-containing phosphatase-2 or Syk may depend on their relative affinities, and could provide a mechanism by which signal transduction from PECAM-1 is internally regulated by both positive and negative signaling enzymes. PMID:22000807

  13. Mechanisms of PECAM-1-mediated cytoprotection and implications for cancer cell survival.

    PubMed

    Bergom, Carmen; Gao, Cunji; Newman, Peter J

    2005-10-01

    Defects in apoptotic pathways can promote cancer development and cause cancers to become resistant to chemotherapy. The cell adhesion and signaling molecule PECAM-1 has been shown to potently suppress apoptosis in a variety of cellular systems. PECAM-1 expression has been reported on a variety of human malignancies-especially hematopoietic and vascular cell cancers-but the significance of this expression has not been fully explored. The ability of PECAM-1 to inhibit apoptosis makes it an attractive candidate as a molecule that may promote cancer development and/or confer resistance to chemotherapeutic treatment. The exact mechanisms by which PECAM-1 mediates its cytoprotection have not been fully defined, but its anti-apoptotic effects have been shown to require both homophilic binding and intracellular signaling via its immunoreceptor tyrosine-based inhibitory motif (ITIM) domains. In this review, we will discuss the data regarding PECAM-1's anti-apoptotic effects and ways in which this cytoprotection may be clinically relevant to the development and/or treatment of hematologic malignancies that express this vascular cell-specific surface molecule. PMID:16194886

  14. PECAM-1 ligation negatively regulates TLR4 signaling in macrophages.

    PubMed

    Rui, Yuxiang; Liu, Xingguang; Li, Nan; Jiang, Yingming; Chen, Guoyou; Cao, Xuetao; Wang, Jianli

    2007-12-01

    Uncontrolled TLR4 signaling may induce excessive production of proinflammatory cytokines and lead to harmful inflammation; therefore, negative regulation of TLR4 signaling attracts much attention now. PECAM-1, a member of Ig-ITIM family, can mediate inhibitory signals in T cells and B cells. However, the role and the mechanisms of PECAM-1 in the regulation of TLR4-mediated LPS response in macrophages remain unclear. In this study, we demonstrate that PECAM-1 ligation with CD38-Fc fusion protein negatively regulates LPS-induced proinflammatory cytokine TNF-alpha, IL-6, and IFN-beta production by inhibiting JNK, NF-kappaB, and IFN regulatory factor 3 activation in macrophages. In addition, PECAM-1 ligation-recruited Src homology region 2 domain-containing phosphatase 1 (SHP-1) and Src homology region 2 domain-containing phosphatase 2 (SHP-2) may be involved in the inhibitory effect of PECAM-1 on TLR4 signaling. Consistently, silencing of PECAM-1 enhances the macrophage response to LPS stimulation. Taken together with the data that PECAM-1 is constitutively expressed in macrophages and its expression is up-regulated by LPS stimulation, PECAM-1 might function as a feedback negative regulator of LPS inflammatory response in macrophages. This study may provide a potential target for intervention of inflammatory diseases. PMID:18025177

  15. Minimal regulation of platelet activity by PECAM-1.

    PubMed

    Dhanjal, Tarvinder S; Ross, Ewan A; Auger, Jocelyn M; McCarty, Owen J T; Hughes, Craig E; Senis, Yotis A; Buckley, Chris D; Watson, Steve P

    2007-02-01

    PECAM-1 is a member of the superfamily of immunoglobulins (Ig) and is expressed on platelets at moderate level. PECAM-1 has been reported to have contrasting effects on platelet activation by the collagen receptor GPVI and the integrin, alphaIIbbeta3, even though both receptors signal through Src-kinase regulation of PLCgamma2. The present study compares the role of PECAM-1 on platelet activation by these two receptors and by the lectin receptor, CLEC-2, which also signals via PLCgamma2. Studies using PECAM-1 knockout-mice and cross-linking of PECAM-1 using specific antibodies demonstrated a minor inhibitory role on platelet responses to the above three receptors and also under some conditions to the G-protein agonist thrombin. The degree of inhibition was considerably less than that produced by PGI2, which elevates cAMP. There was no significant difference in thrombus formation on collagen in PECAM-1-/- platelets relative to litter-matched controls. The very weak inhibitory effect of PECAM-1 on platelet activation relative to that of PGI2 indicate that the Ig-receptor is not a major regulator of platelet activation. PECAM-1 has been reported to have contrasting effects on platelet activation. The present study demonstrates a very mild or negligible effect on platelet activation in response to stimulation by a variety of agonists, thereby questioning the physiological role of the immunoglobulin receptor as a major regulator of platelet activation. PMID:17365855

  16. Recruitment of the adaptor protein Nck to PECAM-1 couples oxidative stress to canonical NF-κB signaling and inflammation.

    PubMed

    Chen, Jie; Leskov, Igor L; Yurdagul, Arif; Thiel, Bonnie; Kevil, Christopher G; Stokes, Karen Y; Orr, A Wayne

    2015-02-24

    Oxidative stress stimulates nuclear factor κB (NF-κB) activation and NF-κB-dependent proinflammatory gene expression in endothelial cells during several pathological conditions, including ischemia/reperfusion injury. We found that the Nck family of adaptor proteins linked tyrosine kinase signaling to oxidative stress-induced activation of NF-κB through the classic IκB kinase-dependent pathway. Depletion of Nck prevented oxidative stress induced by exogenous hydrogen peroxide or hypoxia/reoxygenation injury from activating NF-κB in endothelial cells, increasing the abundance of the proinflammatory molecules ICAM-1 (intracellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) and recruiting leukocytes. Nck depletion also attenuated endothelial cell expression of genes encoding proinflammatory factors but not those encoding antioxidants. Nck promoted oxidative stress-induced activation of NF-κB by coupling the tyrosine phosphorylation of PECAM-1 (platelet endothelial cell adhesion molecule-1) to the activation of p21-activated kinase, which mediates oxidative stress-induced NF-κB signaling. Consistent with this mechanism, treatment of mice subjected to ischemia/reperfusion injury in the cremaster muscle with a Nck inhibitory peptide blocked leukocyte adhesion and emigration and the accompanying vascular leak. Together, these data identify Nck as an important mediator of oxidative stress-induced inflammation and a potential therapeutic target for ischemia/reperfusion injury. PMID:25714462

  17. Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax malaria.

    PubMed

    Ohnishi, K

    1999-02-01

    Elevated plasma or serum levels of thrombomodulin (TM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin have been reported in several diseases. However, plasma or serum levels of TM, ICAM-1, VCAM-1, and E-selectin have not been investigated in the acute phase of Plasmodium vivax malaria. Serum TM, ICAM-1, VCAM-1, E-selectin, and creatinine levels were determined in six Japanese patients in the acute phase of vivax malaria and in seven healthy Japanese controls. Parasitemias of the peripheral blood were < 0.1% in five patients and 0.8% in one patient. The patients' mean +/- SD serum levels of TM, ICAM-1, VCAM-1, and E-selectin were 5.7 +/- 1.3 Fujirebio units/ml, 709 +/- 397 ng/ml, 2,112 +/- 782 ng/ml, and 99 +/- 28 ng/ml, respectively, and all were significantly greater than those in the controls (TM; P < 0.005, ICAM-1; P < 0.025, VCAM-1; P < 0.005, E-selectin; P < 0.025). However, no significant difference was identified between patients and controls for serum creatinine values. The serum levels of TM and VCAM-1 were not related to parasitemia. The elevation of serum TM levels suggests that endothelial cell damage occurs in the acute phase of vivax malaria.

  18. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sezary syndrome

    SciTech Connect

    Nickoloff, B.J.; Griffiths, E.M.; Baadsgaard, O.; Voorhees, J.J.; Hanson, C.A.; Cooper, K.D. )

    1989-04-21

    In mucosis fungoides the malignant T cells express lymphocyte function-associated antigen-1, which allows them to bind to epidermal keratinocytes expressing the gamma interferon-inducible intercellular adhesion molecule-1. In this report, a patient with leukemic-stage mucosis fungoides (Sezary syndrome) had widespread erythematous dermal infiltrates containing malignant T cells, but without any epidermotropism. The authors discovered that the T cells expressed normal amounts of functional lymphocyte function-associated antigen-1, but the keratinocytes did not express significant levels of intercellular adhesion molecule-1, which was probably due to the inability of the malignant T cells to produce gamma interferon. These results support the concept that the inability of malignant T cells to enter the epidermis may contribute to emergence of more clinically aggressive T-cell clones that are no longer confined to the skin, but infiltrate the blood, lymph nodes, and viscera, as is seen in Sezary syndrome.

  19. 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.

    PubMed

    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.

  20. Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus.

    PubMed Central

    Sasseville, V. G.; Newman, W. A.; Lackner, A. A.; Smith, M. O.; Lausen, N. C.; Beall, D.; Ringler, D. J.

    1992-01-01

    AIDS encephalitis is a common sequela to HIV-1 infection in humans and simian immunodeficiency virus (SIVmac) infection in macaques. Although lentiviral-infected macrophages comprise parenchymal inflammatory infiltrates in affected brain tissue, the mechanisms responsible for leukocyte trafficking to the central nervous system in AIDS are unknown. In this study, we investigated the expression of various endothelial-derived leukocyte adhesion proteins in SIVmac-induced AIDS encephalitis. Encephalitic brains from SIVmac-infected macaques, but not uninflamed brains from other SIVmac-infected animals, were found to express abundant vascular cell adhesion molecule-1 (VCAM-1) protein on the majority of arteriolar, venular, and capillary endothelial cells. Soluble VCAM-1 concentrations in cerebrospinal fluid (CSF) from encephalitic animals were increased approximately 20-fold above those from animals without AIDS encephalitis. Expression of other endothelial-related adhesion molecules, including E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1), was not uniformly associated with AIDS encephalitis. Thus, the presence of VCAM-1 in both brain and CSF was uniformly associated with SIVmac-induced disease of the central nervous system, and this expression may, at least in part, influence monocyte and lymphocyte recruitment to the central nervous system during the development of AIDS encephalitis. Moreover, measurement of soluble VCAM-1 in CSF may assist in the clinical assessment of animals or people with AIDS. Images Figure 1 PMID:1279978

  1. Spatial and temporal relationships between cadherins and PECAM-1 in cell-cell junctions of human endothelial cells

    PubMed Central

    1994-01-01

    The integrity of the endothelial layer, which lines the entire cavity of the vascular system, depends on tight adhesion of the cells to the underlying basement membrane as well as to each other. It has been previously shown that such interactions occur via membrane receptors that determine the specificity, topology, and mechanical properties of the surface adhesion. Cell-cell junctions between endothelial cells, in culture and in situ, involve both Ca(2+)-dependent and -independent mechanisms that are mediated by distinct adhesion molecules. Ca(2+)- dependent cell-cell adhesion occurs mostly via members of the cadherin family, which locally anchor the microfilament system to the plasma membrane, in adherens junctions. Ca(2+)-independent adhesions were reported to mainly involve members of the Ig superfamily. In this study, we performed three-dimensional microscopic analysis of the relative subcellular distributions of these two endothelial intercellular adhesion systems. We show that cadherins are located at adjacent (usually more apical), yet clearly distinct domains of the lateral plasma membrane, compared to PECAM-1. Moreover, cadherins were first organized in adherens junctions within 2 h after seeding of endothelial cells, forming multiple lateral patches which developed into an extensive belt-like structure over a period of 24 h. PECAM-1 became associated with surface adhesions significantly later and became progressively associated with the cadherin-containing adhesions. Cadherins and PECAM-1 also differed in their detergent extractability, reflecting differences in their mode of association with the cytoskeleton. Moreover, the two adhesion systems could be differentially modulated since short treatment with the Ca2+ chelator EGTA, disrupted the cadherin junctions leaving PECAM-1 apparently intact. These results confirm that endothelial cells possess distinct intercellular contact mechanisms that differ in their spatial and temporal organization as well as

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

    PubMed

    Goh, Qingnian; Dearth, Christopher L; Corbett, Jacob T; Pierre, Philippe; Chadee, Deborah N; Pizza, Francis X

    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.

  3. Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1.

    PubMed Central

    Sligh, J E; Ballantyne, C M; Rich, S S; Hawkins, H K; Smith, C W; Bradley, A; Beaudet, A L

    1993-01-01

    Gene targeting was used to produce mice deficient in intercellular adhesion molecule 1 (ICAM-1) or CD54, an immunoglobulin-like cell adhesion molecule that binds beta 2 integrins. Homozygous deficient animals develop normally, are fertile, and have a moderate granulocytosis. The nature of the mutation, RNA analysis, and immunostaining are consistent with complete loss of surface expression of ICAM-1. Deficient mice exhibit prominent abnormalities of inflammatory responses including impaired neutrophil emigration in response to chemical peritonitis and decreased contact hypersensitivity to 2,4-dinitrofluorobenzene. Mutant cells provided negligible stimulation in the mixed lymphocyte reaction, although they proliferated normally as responder cells. These mutant animals will be extremely valuable for examining the role of ICAM-1 and its counterreceptors in inflammatory disease processes and atherosclerosis. Images Fig. 1 Fig. 2 PMID:8104338

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

    SciTech Connect

    Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.; Pierre, Philippe; Chadee, Deborah N.; Pizza, Francis X.

    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

  5. PECAM-1 is involved in BCR/ABL signaling and may downregulate imatinib-induced apoptosis of Philadelphia chromosome-positive leukemia cells.

    PubMed

    Wu, Nan; Kurosu, Tetsuya; Oshikawa, Gaku; Nagao, Toshikage; Miura, Osamu

    2013-02-01

    PECAM-1 (CD31) is an immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing surface glycoprotein expressed on various hematopoietic cells as well as on endothelial cells. PECAM-1 has been shown to play roles in regulation of adhesion, migration and apoptosis. The BCR/ABL fusion tyrosine kinase is expressed in chronic myeloid leukemia and Philadelphia-positive (Ph+) acute lymphoblastic leukemia cells, and its inhibition by the clinically used tyrosine kinase inhibitors imatinib or dasatinib induces apoptosis of these cells. In the present study, we demonstrate that PECAM-1 is tyrosine phospho-rylated in its ITIM motifs in various BCR/ABL-expressing cells including primary leukemia cells. Studies using imatinib and dasatinib as well as transient expression experiments in 293T cells revealed that PECAM-1 was phosphorylated directly by BCR/ABL, which was enhanced by the imatinib-resistant E255K and T315I mutations, or partly by the Src family tyrosine kinases, including Lyn, which were activated dependently or independently on BCR/ABL. We also demonstrate by using a substrate trapping mutant of SHP2 that tyrosine phosphorylated PECAM-1 binds SHP2 and is a major substrate for this tyrosine phosphatase in BCR/ABL-expressing cells. Overexpression of PECAM-1 in BCR/ABL-expressing cells, including K562 human leukemia cells, enhanced cell adhesion and partially inhibited imatinib-induced apoptosis involving mitochondria depolarization and caspase-3 cleavage, at least partly, in an ITIM-independent manner. These data suggest that PECAM-1 may play a role in regulation of apoptosis as well as adhesion of BCR/ABL-expressing cells to modulate their imatinib sensitivity and would be a possible candidate for therapeutic target in Ph+ leukemias. PMID:23233201

  6. Mechanotransduction of shear stress occurs through changes in VE-cadherin and PECAM-1 tension: implications for cell migration.

    PubMed

    Conway, Daniel E; Schwartz, Martin A

    2015-01-01

    Recent work has shown that cadherins at cell-cell junctions bear tensile forces. Using novel FRET-based tension sensors, we showed first that in response to shear stress, endothelial cells rapidly reduce mechanical tension on vascular endothelial (VE)-cadherin. Second, we observed a simultaneous increase in tension on platelet endothelial cell adhesion molecule (PECAM)-1, induced by an interaction with vimentin. In this commentary, we discuss how our results fit with existing data on cadherins as important mediators of mechanotransduction, in particular, in cell migration where mechanical tension across cadherins may communicate the direction of movement. The ability of PECAM-1 to bear mechanical tension may also be important in other PECAM-1 functions, such as leukocyte transmigration through the endothelium. Additionally, our observation that vimentin expression was required for PECAM-1 tension and mechanotransduction of fluid flow suggests that intermediate filaments are capable of transmitting tension. Overall, our results argue against models where an external force is passively transferred across the cytoskeleton, and instead suggest that cells actively respond to extracellular forces by modulating tension across junctional proteins.

  7. A novel and critical role for tyrosine 663 in platelet endothelial cell adhesion molecule-1 trafficking and transendothelial migration.

    PubMed

    Dasgupta, Bidisha; Dufour, Eric; Mamdouh, Zahra; Muller, William A

    2009-04-15

    PECAM-1/CD31 is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions. A critical pool of PECAM-1 resides in the lateral border recycling compartment (LBRC). During TEM, membrane from the LBRC is redirected to surround the leukocyte, and this targeted recycling per se is required for TEM. The cytoplasmic domain of PECAM-1 contains two tyrosine residues that have been implicated in PECAM-1 signaling in other cells but never examined in the context of TEM. We found that expression of PECAM-1 imparts on cells the ability to support TEM and that tyrosine 663 (but not tyrosine 686) is required. Furthermore, tyrosine 663 is required for PECAM-1 to efficiently enter and exit the LBRC. Most important, mutation of tyrosine 663 abolishes the ability of the endothelial cells to support targeted recycling of the LBRC. These data define a novel role for tyrosine 663 and suggest that it is part of a recognition motif for trafficking to and/or from the LBRC. PMID:19342684

  8. Molecular Architecture of a Complex between an Adhesion Protein from the Malaria Parasite and Intracellular Adhesion Molecule 1*

    PubMed Central

    Brown, Alan; Turner, Louise; Christoffersen, Stig; Andrews, Katrina A.; Szestak, Tadge; Zhao, Yuguang; Larsen, Sine; Craig, Alister G.; Higgins, Matthew K.

    2013-01-01

    The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria. The PfEMP1 family of adhesive proteins is responsible for this sequestration by mediating interactions with diverse human ligands. In addition, as the primary targets of acquired, protective immunity, the PfEMP1s are potential vaccine candidates. PfEMP1s contain large extracellular ectodomains made from CIDR (cysteine-rich interdomain regions) and DBL (Duffy-binding-like) domains and show extensive variation in sequence, size, and domain organization. Here we use biophysical methods to characterize the entire ∼300-kDa ectodomain from IT4VAR13, a protein that interacts with the host receptor, intercellular adhesion molecule-1 (ICAM-1). We show through small angle x-ray scattering that IT4VAR13 is rigid, elongated, and monomeric. We also show that it interacts with ICAM-1 through the DBLβ domain alone, forming a 1:1 complex. These studies provide a first low resolution structural view of a PfEMP1 ectodomain in complex with its ligand. They show that it combines a modular domain arrangement consisting of individual ligand binding domains, with a defined higher order architecture that exposes the ICAM-1 binding surface to allow adhesion. PMID:23297413

  9. CCN4 induces vascular cell adhesion molecule-1 expression in human synovial fibroblasts and promotes monocyte adhesion.

    PubMed

    Liu, Ju-Fang; Hou, Sheng-Mou; Tsai, Chun-Hao; Huang, Chun-Yin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2013-05-01

    CCN4 is a cysteine-rich protein that belongs to the Cyr61, CTGF, Nov family of matricellular proteins. Here, we investigated the intracellular signaling pathways involved in CCN4-induced vascular cell adhesion molecule-1 expression in human osteoarthritis synovial fibroblasts. Stimulation of OASFs with CCN4 induced VCAM-1 expression. CCN4-induced VCAM-1 expression was attenuated by αvβ5 or α6β1 integrin antibody, Syk inhibitor, PKCδ inhibitor (rottlerin), JNK inhibitor (SP600125), and AP-1 inhibitors (curcumin and tanshinone). Stimulation of cells with CCN4 increased Syk, PKCδ, and JNK activation. Treatment of OASFs with CCN4 also increased c-Jun phosphorylation, AP-1-luciferase activity, and c-Jun binding to the AP-1 element in the VCAM-1 promoter. Moreover, up-regulation of VCAM-1 increased the adhesion of monocytes to OASF monolayers, and this adhesion was attenuated by transfection with a VCAM-1 siRNA. Our results suggest that CCN4 increases VCAM-1 expression in human OASFs via the Syk, PKCδ, JNK, c-Jun, and AP-1 signaling pathways. The CCN4-induced VCAM-1 expression promoted monocyte adhesion to human OASFs. PMID:23313051

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-09-01

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

  12. R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding.

    PubMed

    Yan, Xiaocai; Yan, Mingfei; Guo, Yihe; Singh, Gobind; Chen, Yuhong; Yu, Mei; Wang, Demin; Hillery, Cheryl A; Chan, Andrew M

    2015-01-01

    The trafficking of T-lymphocytes to peripheral draining lymph nodes is crucial for mounting an adaptive immune response. The role of chemokines in the activation of integrins via Ras-related small GTPases has been well established. R-Ras is a member of the Ras-subfamily of small guanosine-5'-triphosphate-binding proteins and its role in T cell trafficking has been investigated in R-Ras null mice (Rras-/-). An examination of the lymphoid organs of Rras-/- mice revealed a 40% reduction in the cellularity of the peripheral lymph nodes. Morphologically, the high endothelial venules of Rras-/- mice were more disorganized and less mature than those of wild-type mice. Furthermore, CD4+ and CD8+ T cells from Rras-/- mice had approximately 42% lower surface expression of L-selectin/CD62L. These aberrant peripheral lymph node phenotypes were associated with proliferative and trafficking defects in Rras-/- T cells. Furthermore, R-Ras could be activated by the chemokine, CCL21. Indeed, Rras-/- T cells had approximately 14.5% attenuation in binding to intercellular adhesion molecule 1 upon CCL21 stimulation. Finally, in a graft-versus host disease model, recipient mice that were transfused with Rras-/- T cells showed a significant reduction in disease severity when compared with mice transplanted with wild-type T cells. These findings implicate a role for R-Ras in T cell trafficking in the high endothelial venules during an effective immune response. PMID:26710069

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

    PubMed

    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. PMID:27152227

  14. Differing roles for B7 and intercellular adhesion molecule-1 in negative selection of thymocytes

    PubMed Central

    1996-01-01

    To ensure self tolerance, immature thymocytes with high binding affinity for self peptides linked to major histocompatibility complex (MHC) molecules are eliminated in situ via apoptosis (negative selection). The roles of two costimulatory molecules, B7-1 and intercellular adhesion molecule-1 (ICAM-1), in negative selection was examined by studying apoptosis of T cell receptor transgenic CD4+8+ thymocytes cultured with specific peptides presented by MHC class I- transfected Drosophila cells. When coexpressed on these cells, B7-1 and ICAM-1 act synergistically and cause strong class 1-restricted negative selection of thymocytes. When expressed separately, however, B7-1 and ICAM-1 display opposite functions: negative selection is augmented by B7-1, but is inhibited by ICAM-1. It is notable that B7-1 is expressed selectively in the thymic medulla, whereas ICAM-1 is expressed throughout the thymus. Because of this distribution, the differing functions of B7-1 and ICAM-1 may dictate the sites of positive and negative selection. Thus, in the cortex, the presence of ICAM-1, but not B7-1, on the cortical epithelium may preclude or reduce negative selection and thereby promote positive selection. Conversely, the combined expression of B7-1 and ICAM-1 may define the medulla as the principal site of negative selection. PMID:8760806

  15. RNA released from necrotic keratinocytes upregulates intercellular adhesion molecule-1 expression in melanocytes.

    PubMed

    Zhang, Shujie; Liu, Shuangchun; Yu, Ning; Xiang, Leihong

    2011-12-01

    Intercellular adhesion molecule-1 (ICAM-1) expression has been detected in melanocytes around active vitiligo patches as well as in surgically transplanted melanocytes. However, it is unclear whether and how skin injury induces the inappropriate expression of ICAM-1 and other proinflammatory genes in melanocytes. We previously reported that human melanocytes expressed TLR3. We hypothesized that the TLR3 expressed in melanocytes may recognize skin injury by binding to the endogenous ligands secreted by the damaged keratinocytes. Here we showed that RNA released from necrotic keratinocytes induced the upregulation of ICAM-1 protein and mRNA, as shown by FACS and real-time RT-PCR. Use of NF-κB inhibitor prevents upregulation of ICAM-1 in melanocytes indicating a direct role of NF-κB in necrotic keratinocyte-mediated upregulation of ICAM-1. Using a shRNA-expressing lentivirus, we demonstrated that in human melanocytes, TLR3 seems to be necessary for the upregulation of ICAM-1. Using oligonucleotide microarray, we demonstrated a dramatic increase in proinflammatory cytokine and chemokine transcripts (CXCL10, CXCL11, TNFSF10, CCL5, CCL4, CCL2, IFNB1, CCL20, IL-8, and CCL11). These observations suggested that RNA released from necrotic keratinocytes might act as an endogenous TLR3 ligand for the stimulation of ICAM-1 and other proinflammatory gene expression in human melanocytes, which might be involved in the pathogenesis of vitiligo following skin physical trauma.

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

    PubMed Central

    Wensing, Kristina U.; Eggert, Hendrik; Scharsack, Jörn P.

    2016-01-01

    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. PMID:27152227

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

    PubMed Central

    Mehrabian, Mohadeseh; Brethour, Dylan; Wang, Hansen; Xi, Zhengrui; Rogaeva, Ekaterina; Schmitt-Ulms, Gerold

    2015-01-01

    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. PMID:26288071

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

    PubMed

    Mehrabian, Mohadeseh; Brethour, Dylan; Wang, Hansen; Xi, Zhengrui; Rogaeva, Ekaterina; Schmitt-Ulms, Gerold

    2015-01-01

    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. PMID:26288071

  19. Functional studies of truncated soluble intercellular adhesion molecule 1 expressed in Escherichia coli.

    PubMed Central

    Martin, S; Martin, A; Staunton, D E; Springer, T A

    1993-01-01

    We have expressed in Escherichia coli the two N-terminal immunoglobulin (Ig)-like domains of the intercellular adhesion molecule 1 (ICAM-1). The first 188 residues of ICAM-1 were expressed with an N-terminal methionine (MP188) or as a maltose-binding fusion protein which was cleaved with factor Xa (XP188). After refolding, both MP188 and XP188 were active in binding to the leukocyte integrin lymphocyte function-associated antigen 1, which has previously been shown to bind to the N-terminal Ig domain of ICAM-1. The major group of rhinoviruses and malaria-infected erythrocytes bind to distinct sites within the first Ig-like domain of ICAM-1. Both MP188 and XP188 bound to malaria-infected erythrocytes; however, only XP188 inhibited human rhinovirus plaque formation. A product (MdQ1P188) with the initiation methionine fused to residue 2, i.e., with glutamine 1 deleted, inhibited plaque formation. MdQ1P188 was able to induce a conformational change of the virus capsid as shown by conversion of 149S particles to 85S particles, whereas MP188 had no effect. These results show that functionally active fragments of ICAM-1 can be produced in E. coli, that glycosylation is not required for ligand binding, and that the N-terminal residue of ICAM-1 is proximal to or part of the human rhinovirus-binding site. Images PMID:8101071

  20. Role of Intercellular Adhesion Molecule-1 in Radiation-Induced Brain Injury

    SciTech Connect

    Wu, K.-L.; Tu Ba; Li Yuqing; Wong, C. Shun

    2010-01-15

    Purpose: To determine the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of brain injury after irradiation (IR). Methods and Materials: We assessed the expression of ICAM-1 in mouse brain after cranial IR and determined the histopathologic and behavioral changes in mice that were either wildtype (+/+) or knockout (-/-) of the ICAM-1 gene after IR. Results: There was an early dose-dependent increase in ICAM-1 mRNA and protein expression after IR. Increased ICAM-1 immunoreactivity was observed in endothelia and glia of ICAM-1+/+ mice up to 8 months after IR. ICAM-1-/- mice showed no expression. ICAM-1+/+ and ICAM-1-/- mice showed similar vascular abnormalities at 2 months after 10-17 Gy, and there was evidence for demyelination and inhibition of hippocampal neurogenesis at 8 months after 10 Gy. After 10 Gy, irradiated ICAM-1+/+ and ICAM-1-/- mice showed similar behavioral changes at 2-6 months in open field, light-dark chamber, and T-maze compared with age-matched genotype controls. Conclusion: There is early and late upregulation of ICAM-1 in the vasculature and glia of mouse brain after IR. ICAM-1, however, does not have a causative role in the histopathologic injury and behavioral dysfunction after moderate single doses of cranial IR.

  1. Polymorphisms in the intercellular adhesion molecule 1 gene and cancer risk: a meta-analysis

    PubMed Central

    Tang, Weifeng; Wang, Yafeng; Chen, Yuanmei; Gu, Haiyong; Chen, Shuchen; Kang, Mingqiang

    2015-01-01

    Objectives: The correlation between intercellular adhesion molecule 1 (ICAM-1) common polymorphisms (rs5498 A>G and rs3093030 C>T) and cancer susceptibility has been explored in various ethnic groups and different cancer types; however, these investigations have yielded contradictory results. To address the relationship more precisely, we performed this meta-analysis. Design and methods: EmBase, PubMed and China National Knowledge Infrastructure (CNKI) databases were searched by two authors independently for eligible publications before April 8, 2015. Random-effects or fixed-effects model was harnessed to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) when appropriate. Results: The result suggested that the ICAM-1 rs5498 A>G polymorphism is not associated with cancer susceptibility in overall cancer. In a stratified analysis by ethnicity, a significant increased cancer risk was identified among Asians, but the inverse association was found among Caucasians. In a stratified analysis by cancer type, ICAM-1 rs5498 A>G polymorphism was associated with a significantly increased risk of oral cancer, but with protection from colorectal cancer and melanoma. ICAM-1 rs3093030 C>T polymorphism is not correlated with cancer susceptibility. Conclusions: In summary, this meta-analysis highlights that the ICAM-1 rs5498 A>G polymorphism probably contributes to decreased susceptibility to cancer, especially in Caucasians, in melanoma and colorectal cancer subgroup, but it may be a risk factor for oral cancer and Asians. PMID:26550112

  2. Medullary carcinoma is associated with expression of intercellular adhesion molecule-1. Implication to its morphology and its clinical behavior.

    PubMed Central

    Bacus, S. S.; Zelnick, C. R.; Chin, D. M.; Yarden, Y.; Kaminsky, D. B.; Bennington, J.; Wen, D.; Marcus, J. N.; Page, D. L.

    1994-01-01

    The histological hallmarks for the diagnosis of medullary breast cancer are circumscription, syncytial architecture, diffuse inflammatory infiltrate, and highly atypical nuclei. The biological and prognostic implication is a lower propensity to metastasize. We studied 19 medullary carcinomas for expression of the intercellular adhesion molecule-1 and lymphocyte-function-associated antigen-1, Neu differentiation factor, tumor necrosis factor-alpha, and the expression of HER-2/neu, HER-4, and HER-3 receptors. Our study revealed that all of the 19 medullary carcinomas expressed the intercellular adhesion molecule-1 and lymphocyte function associated antigen. Eighteen of 19 cancers expressed Neu differentiation factor and tumor necrosis factor-alpha. All medullary cancers expressed the HER-2/neu receptor, however, in the majority of the cases, the staining was confined to the cytoplasm. Only 4 of 12 cancers expressed HER-4 and none of the eight medullary cancers tested expressed HER-3. By comparison, in a control group of infiltrating ductal carcinomas, expression of intercellular adhesion molecule-1, lymphocyte function associated antigen-1, and Neu differentiation factor was positive in about 25 to 30% of the cases, HER-4 was expressed in 75% and HER-3 in 95% of the cases. Taken together, our observations suggest that the expression of intercellular adhesion molecule-1, lymphocyte function associated antigen, Neu differentiation factor, and tumor necrosis factor-alpha as factors that may affect the special morphology and the biological behavior that characterizes medullary carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7992839

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

    PubMed Central

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

    1993-01-01

    To elucidate the mechanism(s) of myocardial reperfusion injury, we investigated the roles of cell adhesion molecules on both leukocytes and vascular endothelial cells in the reperfused myocardia. We found that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia and clarified, for the first time, that the expression of intercellular adhesion molecule-1 was enhanced on the capillary and venous endothelial cells from 8 to 96 hours after the start of reperfusion. Furthermore, pretreatment with individual monoclonal antibodies against cell adhesion molecules (CD11a, CD11bc, CD18, and intercellular adhesion molecule-1) reduced not only the infiltration of leukocytes but also the area of infarction in the reperfused hearts. These observations suggest that cell adhesion molecules play a critical role in the pathogenesis of myocardial reperfusion injury. Images Figure 2 Figure 3 Figure 4 PMID:8102030

  4. Endothelial activation by hydrogen peroxide. Selective increases of intercellular adhesion molecule-1 and major histocompatibility complex class I.

    PubMed Central

    Bradley, J. R.; Johnson, D. R.; Pober, J. S.

    1993-01-01

    Products of activated leukocytes may alter vascular endothelial cell (EC) function. For example, ECs respond to leukocyte-derived cytokines, such as tumor necrosis factor (TNF) or interleukin-1, by reversibly altering levels of expression of specific gene products that promote inflammation. In contrast, hydrogen peroxide, a product of TNF-activated neutrophils, can produce irreversible EC injury and death. In this study, we have investigated the effects of subinjurious concentrations of hydrogen peroxide on EC inflammatory functions. Treatment with 50 to 100 mumol/L hydrogen peroxide selectively increases surface expression of intercellular adhesion molecule-1 and major histocompatibility complex class I, but not endothelial leukocyte adhesion molecule-1 (also known as E-selectin), vascular cell adhesion molecule-1, or gp96, a constitutively expressed EC surface protein. Increased major histocompatibility complex class I and intercellular adhesion molecule-1 surface expression is associated with specifically increased messenger RNA levels, suggesting selective endothelial gene activation. Hydrogen peroxide does not activate the transcription factor Nuclear Factor kappa B, an important mediator of TNF-induced gene expression. Co-treatment with hydrogen peroxide inhibits TNF-induced gene expression at 4 hours, an effect which can be attributed to reversible inhibition of TNF binding to EC surface receptors. Hydrogen peroxide also antagonizes the actions of interleukin-1. At 24 hours, TNF and hydrogen peroxide produce, at most, additive increases in intercellular adhesion molecule-1 and major histocompatibility complex class I. These results suggest that subinjurious concentrations of hydrogen peroxide can activate endothelium and that the effects of hydrogen peroxide on ECs differ from those of inflammatory cytokines. Images Figure 3 Figure 4 Figure 5 PMID:8098585

  5. Differential up-regulation of circulating soluble and endothelial cell intercellular adhesion molecule-1 in mice.

    PubMed Central

    Komatsu, S.; Flores, S.; Gerritsen, M. E.; Anderson, D. C.; Granger, D. N.

    1997-01-01

    Although circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) are frequently used as an indicator of the severity of different immune, inflammatory, or neoplastic diseases, little is known about the factors that govern plasma sICAM-1 concentration and its relationship to the membranous form of ICAM-1 (mICAM-1) expressed on vascular endothelial cells. Plasma sICAM-1 concentration (measured by enzyme-linked immunosorbent assay) and mICAM-1 expression (measured using the dual radiolabeled monoclonal antibody technique) in different vascular beds (eg, lung, small intestine, and spleen) were monitored in wild-type (C57BL) and ICAM-1-deficient mice, before and after administration of tumor necrosis factor (TNF)-alpha. In wild-type mice, TNF-alpha elicited time-dependent increases in lung and intestine mICAM-1 (plateau achieved at 12 hours), with a corresponding increase in plasma sICAM-1 (peaked at 5 hours and then declined). The initial increases in mICAM-1 and pulmonary leukocyte sequestration (measured as lung myeloperoxidase activity) induced by TNF-alpha preceded any detectable elevation in sICAM-1. In ICAM-1-deficient mice, plasma sICAM-1 was reduced by approximately 70%, with > 95% reductions of mICAM-1 in lung and intestine, and > 75% reduction in splenic accumulation of anti-ICAM-1 antibody. Although TNF-alpha doubled plasma sICAM-1 in ICAM-1-deficient mice, mICAM-1 was unaffected in all tissues. Either splenectomy or pretreatment with cycloheximide resulted in an attenuated TNF-induced increase in sICAM-1, without affecting mICAM-1 expression. These findings indicate that plasma sICAM-1 concentration does not accurately reflect the level of ICAM-1 expression on endothelial cells in different vascular beds. PMID:9212746

  6. R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding

    PubMed Central

    Yan, Xiaocai; Yan, Mingfei; Guo, Yihe; Singh, Gobind; Chen, Yuhong; Yu, Mei; Wang, Demin; Hillery, Cheryl A.; Chan, Andrew M.

    2015-01-01

    The trafficking of T-lymphocytes to peripheral draining lymph nodes is crucial for mounting an adaptive immune response. The role of chemokines in the activation of integrins via Ras-related small GTPases has been well established. R-Ras is a member of the Ras-subfamily of small guanosine-5’-triphosphate-binding proteins and its role in T cell trafficking has been investigated in R-Ras null mice (Rras−/−). An examination of the lymphoid organs of Rras−/− mice revealed a 40% reduction in the cellularity of the peripheral lymph nodes. Morphologically, the high endothelial venules of Rras−/− mice were more disorganized and less mature than those of wild-type mice. Furthermore, CD4+ and CD8+ T cells from Rras−/− mice had approximately 42% lower surface expression of L-selectin/CD62L. These aberrant peripheral lymph node phenotypes were associated with proliferative and trafficking defects in Rras−/− T cells. Furthermore, R-Ras could be activated by the chemokine, CCL21. Indeed, Rras−/− T cells had approximately 14.5% attenuation in binding to intercellular adhesion molecule 1 upon CCL21 stimulation. Finally, in a graft-versus host disease model, recipient mice that were transfused with Rras−/− T cells showed a significant reduction in disease severity when compared with mice transplanted with wild-type T cells. These findings implicate a role for R-Ras in T cell trafficking in the high endothelial venules during an effective immune response. PMID:26710069

  7. Carcinoembryonic Antigen Cell Adhesion Molecule 1 long isoform modulates malignancy of poorly differentiated colon cancer cells

    PubMed Central

    Arabzadeh, Azadeh; Dupaul-Chicoine, Jeremy; Breton, Valérie; Haftchenary, Sina; Yumeen, Sara; Turbide, Claire; Saleh, Maya; McGregor, Kevin; Greenwood, Celia M T; Akavia, Uri David; Blumberg, Richard S; Gunning, Patrick T; Beauchemin, Nicole

    2015-01-01

    Objective Nearly 20%–29% of patients with colorectal cancer (CRC) succumb to liver or lung metastasis and there is a dire need for novel targets to improve the survival of patients with metastasis. The long isoform of the Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1-L or CC1-L) is a key regulator of immune surveillance in primary CRC, but its role in metastasis remains largely unexplored. We have examined how CC1-L expression impacts on colon cancer liver metastasis. Design Murine MC38 transfected with CC1-L were evaluated in vitro for proliferation, migration and invasion, and for in vivo experimental liver metastasis. Using shRNA silencing or pharmacological inhibition, we delineated the role in liver metastasis of Chemokine (C-C motif) Ligand 2 (CCL2) and Signal Transducer and Activator of Transcription 3 (STAT3) downstream of CC1-L. We further assessed the clinical relevance of these findings in a cohort of patients with CRC. Results MC38-CC1-L-expressing cells exhibited significantly reduced in vivo liver metastasis and displayed decreased CCL2 chemokine secretion and reduced STAT3 activity. Down-modulation of CCL2 expression and pharmacological inhibition of STAT3 activity in MC38 cells led to reduced cell invasion capacity and decreased liver metastasis. The clinical relevance of our findings is illustrated by the fact that high CC1 expression in patients with CRC combined with some inflammation-regulated and STAT3-regulated genes correlate with improved 10-year survival. Conclusions CC1-L regulates inflammation and STAT3 signalling and contributes to the maintenance of a less-invasive CRC metastatic phenotype of poorly differentiated carcinomas. PMID:25666195

  8. Expression of intercellular adhesive molecule-1 in liver cancer tissues andliver cancer metastasis

    PubMed Central

    Sun, Jing-Jing; Zhou, Xin-Da; Zhou, Ge; Liu, Yin-Kun

    1998-01-01

    AIM: To study the relationship between intercellular adhesive molecule-1 (ICAM-1) and liver cancer metastasis and to search for factors to predict metastasis of liver cancer. METHODS: ICAM-1 expression in fresh tissues of normal liver and hepatocellular cancer (HCC) was examined by immunoperoxidase staining. The expression of ICAM-1 in human hepatoma, tumor surrounding tissues and normal livers were semiquantitatively analyzed by Dot immuno blot. Tissue ICAM-1 expression at mRNA level was detected by Northern blot. RESULTS: All 6 cases of normal liver samples were negative in anti-ICAM-1 immunohistochemical staining, 80.0% (36/45) of HCC presented various ICAM-1 expression. The number of positive cells was a little higher in large tumors, tumors with intact capsule and metastasis, but there was no significant difference. Two cases with cancer embolus also had high ICAM-1 expression. ICAM-1 concentration in HCC (13.43 ± 0.09) was higher than that in tumor surrounding tissues (5.89 ± 0.17, P < 0.01) and normal livers (4.27 ± 0.21, P < 0.01). It was also higher in metastasis group (20.24 ± 0.30) than in nonmetastasis group (10.23 ± 0.12, P < 0.05). Northern blot analysis revealed that ICAM-1 expression at mRNA level was also higher in HCC and cancer embolus than that in tumor surrounding tissues and normal livers. CONCLUSION: Tissue ICAM-1 could indicate the growth and metastasis of HCC, and may be an index that can predict liver cancer metastasis. PMID:11819275

  9. Expression of intercellular adhesion molecule-1 on macrophages in vitro as a marker of activation.

    PubMed

    Bernatchez, S F; Atkinson, M R; Parks, P J

    1997-10-01

    Macrophage activation is a major component of wound healing. It also determines the extent of inflammatory reactions and the response of the body to implanted materials. We have previously shown, using an in vitro model, that the extent of spreading of macrophages on different materials is a marker of activation, and that a soluble inducer has a dose-response effect on the secretion of cytokines in the culture medium. This work investigates the expression of three different cell surface markers [macrophages MAC-1, MAC-3 and intercellular adhesion molecule-1 (ICAM-1)] on macrophages in vitro using confocal microscopy and shows that ICAM-1 is also a marker of macrophage activation in this model. We observed increased amounts of ICAM-1 on activated macrophages compared to unactivated macrophages, whereas MAC-1 and MAC-3 were either expressed constitutively or demonstrated no quantitative change in expression after activation under the same experimental conditions. We also tested the expression of ICAM-1 with various concentrations of soluble inducers (lipopolysaccharide, 0.001, 0.01, 0.1, 1 and 10 micrograms ml-1. S-27609, 0.1, 0.25, 0.5, 1, 2 and 3 micrograms ml-1 and on a sheet of polylactic acid alone or in combination with soluble inducers. All doses of soluble inducers induced the expression of ICAM-1 on cells grown in glass chamber slides. The induction was not dose related but seemed to work rather in an on-off manner. There was no effect of material on ICAM-1 expression on the cell surface when no soluble inducer was added. This was similar to cytokine secretion, which was not induced by our material alone. When either lipopolysaccharide or S-27609 was used in combination with the material, there was an increase in the average measured intensity of ICAM-1. In this in vitro model, ICAM-1 staining as measured by confocal microscopy is a marker for macrophage activation. Our results suggest that the extent of macrophage activation as measured by ICAM-1 and by

  10. Synchronous elevation of soluble intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) correlates with gastric cancer progression.

    PubMed

    Yoo, N C; Chung, H C; Chung, H C; Park, J O; Rha, S Y; Kim, J H; Roh, J K; Min, J S; Kim, B S; Noh, S H

    1998-02-01

    Soluble forms of ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) have been reported from the supernatant of cytokine-activated endothelial cells, cancer cells and from sera of cancer patients. We measured sICAM-1 and sVCAM-1 from the serum of 20 healthy volunteers and 142 gastric cancer patients by ELISA assay. Ninety-five patients were operable and 47 patients were in-operable at the time of this study. Particularly in the 28 operable patients, we sampled both portal and peripheral blood simultaneously and measured the levels of the soluble forms of cell adhesion molecules (sCAMs). The sCAMs level and sero-positivity rate increased with cancer progression in order of the healthy controls, operable patients, and inoperable patients. In in-operable cancer, the sICAM-1 level increased more with liver metastasis. sICAM-1 and sVCAM-1 did not correlate with each other in either portal or peripheral blood. A total of 58.3% of patients with liver metastasis and 22.9% of patients without liver metastasis showed synchronous expression of both sCAMs (p = 0.03). Synchronous sero-positivity of sCAMs and alpha FP was higher with liver metastasis (p = 0.01). The median overall survival duration which co-expressed both sCAMs was 9 months. This showed a significant difference compared with the sICAMs non-expressing group, where the median survival was not reached until 24 months follow-up (p = 0.002). The synchronous expression of sCAMs was an independent risk factor in gastric cancer patients. We raise the possibility that synchronous sICAM-1 and sVCAM-1 elevation may be a useful monitor to determine tumor burden in gastric cancer.

  11. The role of endothelial cell adhesion molecules P-selectin, E-selectin and intercellular adhesion molecule-1 in leucocyte recruitment induced by exogenous methylglyoxal.

    PubMed

    Su, Yang; Lei, Xi; Wu, Lingyun; Liu, Lixin

    2012-09-01

    Methylglyoxal (MG) is a reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. In hyperglycaemic conditions, increased MG level has been linked to the development of diabetes and its vascular complications at the macrovascular and microvascular levels where inflammation plays a role. To study the mechanism of MG-induced inflammation in vivo, we applied MG locally to healthy mice and used intravital microscopy to investigate the role of endothelial cell adhesion molecules in MG-induced leucocyte recruitment in cremasteric microvasculature. Administration of MG (25 and 50 mg/kg) to the tissue dose-dependently induced leucocyte recruitment at 4.0-5.5 hr, with 84-92% recruited cells being neutrophils. Such MG treatment up-regulated the expression of endothelial cell adhesion molecules P-selectin, E-selectin, intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1. Activation of the nuclear factor-κB signalling pathway contributed to MG-induced up-regulation of these adhesion molecules and leucocyte recruitment. The role of the up-regulated endothelial cell adhesion molecules in MG-induced leucocyte recruitment was determined by applying specific functional blocking antibodies to MG-treated animals and observing changes in leucocyte recruitment parameters. Our data demonstrate that the up-regulation of P-selectin, E-selectin and intercellular adhesion molecule-1 contributes to the increased leucocyte rolling flux, reduced leucocyte rolling velocity, and increased leucocyte adhesion, respectively. Our results reveal the role of endothelial cell adhesion molecules in MG-induced leucocyte recruitment in microvasculature, an inflammatory condition related to diabetic vascular complications.

  12. The role of endothelial cell adhesion molecules P-selectin, E-selectin and intercellular adhesion molecule-1 in leucocyte recruitment induced by exogenous methylglyoxal

    PubMed Central

    Su, Yang; Lei, Xi; Wu, Lingyun; Liu, Lixin

    2012-01-01

    Methylglyoxal (MG) is a reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. In hyperglycaemic conditions, increased MG level has been linked to the development of diabetes and its vascular complications at the macrovascular and microvascular levels where inflammation plays a role. To study the mechanism of MG-induced inflammation in vivo, we applied MG locally to healthy mice and used intravital microscopy to investigate the role of endothelial cell adhesion molecules in MG-induced leucocyte recruitment in cremasteric microvasculature. Administration of MG (25 and 50 mg/kg) to the tissue dose-dependently induced leucocyte recruitment at 4·0–5·5 hr, with 84–92% recruited cells being neutrophils. Such MG treatment up-regulated the expression of endothelial cell adhesion molecules P-selectin, E-selectin, intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1. Activation of the nuclear factor-κB signalling pathway contributed to MG-induced up-regulation of these adhesion molecules and leucocyte recruitment. The role of the up-regulated endothelial cell adhesion molecules in MG-induced leucocyte recruitment was determined by applying specific functional blocking antibodies to MG-treated animals and observing changes in leucocyte recruitment parameters. Our data demonstrate that the up-regulation of P-selectin, E-selectin and intercellular adhesion molecule-1 contributes to the increased leucocyte rolling flux, reduced leucocyte rolling velocity, and increased leucocyte adhesion, respectively. Our results reveal the role of endothelial cell adhesion molecules in MG-induced leucocyte recruitment in microvasculature, an inflammatory condition related to diabetic vascular complications. PMID:22681228

  13. Micromanipulation of adhesion of phorbol 12-myristate-13-acetate-stimulated T lymphocytes to planar membranes containing intercellular adhesion molecule-1.

    PubMed Central

    Tözeren, A; Mackie, L H; Lawrence, M B; Chan, P Y; Dustin, M L; Springer, T A

    1992-01-01

    This paper presents an analytical and experimental methodology to determine the physical strength of cell adhesion to a planar membrane containing one set of adhesion molecules. In particular, the T lymphocyte adhesion due to the interaction of the lymphocyte function associated molecule 1 on the surface of the cell, with its counter-receptor, intercellular adhesion molecule-1 (ICAM-1), on the planar membrane, was investigated. A micromanipulation method and mathematical analysis of cell deformation were used to determine (a) the area of conjugation between the cell and the substrate and (b) the energy that must be supplied to detach a unit area of the cell membrane from its substrate. T lymphocytes stimulated with phorbol 12-myristate-13-acetate (PMA) conjugated strongly with the planar membrane containing purified ICAM-1. The T lymphocytes attached to the planar membrane deviated occasionally from their round configuration by extending pseudopods but without changing the size of the contact area. These adherent cells were dramatically deformed and then detached when pulled away from the planar membrane by a micropipette. Detachment occurred by a gradual decrease in the radius of the contact area. The physical strength of adhesion between a PMA-stimulated T lymphocyte and a planar membrane containing 1,000 ICAM-1 molecules/micron 2 was comparable to the strength of adhesion between a cytotoxic T cell and its target cell. The comparison of the adhesive energy density, measured at constant cell shape, with the model predictions suggests that the physical strength of cell adhesion may increase significantly when the adhesion bonds in the contact area are immobilized by the actin cytoskeleton. Images FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 8 FIGURE 9 PMID:1358239

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

    PubMed

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

    2014-06-01

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

  15. [Crucial roles of PECAM-1 in shear stress sensing of vascular endothelial cells].

    PubMed

    Masuda, Michitaka; Kogata, Naoko; Mochizuki, Naoki

    2004-11-01

    Fluid shear stress (FSS) induces many forms of responses, including phosphorylation of ERK in endothelial cells (ECs). We have earlier reported that FSS and hyper-osmotic shock rapidly induce tyrosine phosphorylation of PECAM-1 (CD31). The phosphorylated PECAM-1 acts as a plasma membrane anchoring site for SHP2, a protein tyrosine phosphatase involved in the signal transmission from receptor tyrosine kinases to ERK. Osmotic shock also induces transient ERK activation in ECs. The osmotic-shock-induced ERK activation but not p38 MAP kinase activation was dependent on the PECAM-1 engagement and was blocked by its downregulation. When magnetic beads coated with antibodies against the extracellular domain of PECAM-1 were attached to ECs and tugged by magnetic force, PECAM-1 associated with the beads was tyrosine phosphorylated. ERK was also phosphorylated in these cells. Binding of the beads by itself or pulling on the cell surface using poly-L-lysine coated beads did not induce phosphorylation of PECAM-1 and ERK. These results suggest that PECAM-1 is a mechanotransduction molecule. PMID:15502396

  16. S fimbriae of uropathogenic Escherichia coli bind to primary human renal proximal tubular epithelial cells but do not induce expression of intercellular adhesion molecule 1.

    PubMed Central

    Kreft, B; Placzek, M; Doehn, C; Hacker, J; Schmidt, G; Wasenauer, G; Daha, M R; van der Woude, F J; Sack, K

    1995-01-01

    We have recently reported an increase of expression of the intercellular adhesion molecule 1 by renal carcinoma cells in response to S fimbriae of Escherichia coli. Now we demonstrate that E. coli expressing S and P fimbriae strongly binds to human proximal tubular epithelial cells. However, in primary and simian virus 40-transfected renal tubular epithelial cells S fimbriae do not enhance the expression of intercellular adhesion molecule 1. PMID:7622256

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

    PubMed

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

    2010-01-01

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

  18. Benzo[a]pyrene induces intercellular adhesion molecule-1 through a caveolae and aryl hydrocarbon receptor mediated pathway

    SciTech Connect

    Oesterling, Elizabeth; Toborek, Michal; Hennig, Bernhard

    2008-10-15

    Toxicologic and epidemiologic studies have linked benzo[a]pyrene (B[a]P) exposure with cardiovascular diseases such as atherosclerosis. The mechanisms of action leading to these diseases have not been fully understood. One key step in the development of atherosclerosis is vascular endothelial dysfunction, which is characterized by increased adhesiveness. To determine if B[a]P could lead to increased endothelial adhesiveness, the effects of B[a]P on human endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression was investigated. B[a]P was able to increase ICAM-1 protein only after pretreatment with the aryl hydrocarbon receptor (AhR) agonist {beta}-naphthoflavone ({beta}-NF). Knockdown of AhR by siRNA or treatment with AhR antagonist {alpha}-naphthoflavone ({alpha}-NF) eliminated the induction of ICAM-1 from B[a]P, confirming the necessity of AhR in this process. Likewise, B[a]P only increased monocyte adhesion to the vascular endothelium when cells were pretreated with {beta}-NF. Experiments were done to define a signaling mechanism. B[a]P increased phosphorylation of MEK and p38-MAPK, and inhibitors to these proteins blunted the ICAM-1 induction. B[a]P was also able to increase AP-1 DNA binding and phosphorylation of cJun. Phosphorylation of cJun was disrupted by MEK and p38-MAPK inhibitors linking the signaling cascade. Finally, the importance of membrane microdomains, caveolae, was demonstrated by knockdown of the structural protein caveolin-1. Disruption of caveolae eliminated the B[a]P-induced ICAM-1 expression. These data suggest a possible pro-inflammatory mechanism of action of B[a]P involving caveolae, leading to increased vascular endothelial adhesiveness, and this inflammation may be a critical step in the development of B[a]P-induced atherosclerosis.

  19. Intercellular Adhesion Molecule 1 and Progression of Percent Emphysema: The MESA Lung Study

    PubMed Central

    Aaron, Carrie P.; Schwartz, Joseph E.; Bielinski, Suzette J.; Hoffman, Eric A.; Austin, John H. M.; Oelsner, Elizabeth C.; Donohue, Kathleen M.; Kalhan, Ravi; Berardi, Cecilia; Kaufman, Joel D.; Jacobs, David R.; Tracy, Russell P.; Barr, R.Graham

    2014-01-01

    Endothelial intercellular adhesion molecule (ICAM) 1 binds neutrophils and facilitates their transmigration into the lung; E-selectin facilitates leukocyte rolling. As neutrophils contribute to tissue destruction in emphysema and chronic obstructive pulmonary disease, we hypothesized that soluble ICAM-1 (sICAM-1) and E-selectin (sE-selectin) would be associated with longitudinal progression of emphysema and lung function decline. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45-84 years old without clinical cardiovascular disease in 2000-02. The MESA Lung Study assessed percent emphysema (<-950 Hounsfield units) on cardiac (2000-07) and full-lung CT scans (2010-12), and spirometry was assessed twice over five years. sICAM-1 and sE-selectin were measured at baseline. Mixed-effect models adjusted for demographics, anthropometry, smoking, C-reactive protein, sphingomyelin and scanner factors. Among 1,865 MESA Lung participants with measurement of sICAM-1 and percent emphysema the mean log-sICAM-1 was 5.5±0.3 ng/mL and percent emphysema increased 0.73 percentage points (95% CI: 0.34, 1.12; P<0.001) over ten years. A one SD increase in sICAM-1 was associated with an accelerated increase in percent emphysema of 0.23 percentage points over ten years (95% CI: 0.06, 0.39; P=0.007). No significant association was found for sE-selectin, or between any adhesion molecule and lung function. Higher levels of sICAM-1 were independently associated with progression of percent emphysema in a general population sample. PMID:25457724

  20. Interleukin 3 stimulates proliferation and triggers endothelial-leukocyte adhesion molecule 1 gene activation of human endothelial cells.

    PubMed

    Brizzi, M F; Garbarino, G; Rossi, P R; Pagliardi, G L; Arduino, C; Avanzi, G C; Pegoraro, L

    1993-06-01

    Proliferation and functional activation of endothelial cells within a tissue site of inflammation are regulated by humoral factors released by cells, such as T lymphocytes and monocytes, infiltrating the perivascular space. In the present study we investigated the effects of interleukin 3 (IL-3), an activated T lymphocyte-derived cytokine, on cultured human umbilical vein endothelial cells (HUVEC). Proliferative activity, evaluated both by estimation of the fraction of cells in the S phase and by direct cell count demonstrated that IL-3, at the dose of 25 ng/ml, enhances more than threefold both DNA synthesis and cell proliferation above baseline control conditions. Binding studies with radioiodinated ligand demonstrated that HUVEC constitutively express a smaller number of IL-3 binding sites (approximately 99 binding sites per cell, with an apparent Kd of 149 pM). Accordingly, molecular analysis showed the presence of transcripts for both alpha and beta subunits of the IL-3 receptor. Functional activation of endothelial cells was evaluated by the expression of the endothelial-leukocyte adhesion molecule 1 (ELAM-1) transcript and by leukocyte adhesion. The ELAM-1 gene transcript was clearly detectable 4 h after IL-3 addition and started to decrease after 12 h. Moreover, IL-3-induced ELAM-1 transcription was followed by enhanced adhesion of neutrophils and CD4+ T cells to HUVEC. The findings that IL-3 can stimulate both proliferation and functional activation of endothelial cells suggest that this cytokine can be involved in sustaining the process of chronic inflammation.

  1. Epidermal Expression of Intercellular Adhesion Molecule 1 is Not a Primary Inducer of Cutaneous Inflammation in Transgenic Mice

    NASA Astrophysics Data System (ADS)

    Williams, Ifor R.; Kupper, Thomas S.

    1994-10-01

    Keratinocytes at sites of cutaneous inflammation have increased expression of intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice were prepared in which the expression of mouse ICAM-1 was targeted to basal keratinocytes by using the human K14 keratin promoter. The level of constitutive expression attained in the transgenic mice exceeded the peak level of ICAM-1 expression induced on nontransgenic mouse keratinocytes in vitro by optimal combinations of interferon γ and tumor necrosis factor α or in vivo by proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro adhesion assays demonstrated that cultured transgenic keratinocytes were superior to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional form. However, the high level of constitutive ICAM-1 expression achieved on keratinocytes in vivo in these transgenic mice did not result in additional recruitment of CD45^+ leukocytes into transgenic epidermis, nor did it elicit dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate contact-hypersensitivity reactions to epicutaneous application of haptens. The absence of a spontaneous phenotype in these transgenic mice was not the result of increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were equal in transgenic mice and controls. We conclude that elevated ICAM-1 expression on keratinocytes cannot act independently to influence leukocyte trafficking and elicit cutaneous inflammation.

  2. Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

    PubMed

    Meng, Charles Q; Ni, Liming; Worsencroft, Kimberly J; Ye, Zhihong; Weingarten, M David; Simpson, Jacob E; Skudlarek, Jason W; Marino, Elaine M; Suen, Ki-Ling; Kunsch, Charles; Souder, Amy; Howard, Randy B; Sundell, Cynthia L; Wasserman, Martin A; Sikorski, James A

    2007-03-22

    Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP values and inhibitory efficacy were observed among structurally similar compounds of the series. Various substituents were found to be tolerated at several positions of the chalcone backbone as long as the compounds fell into the right range of lipophilicity. The chalcone alpha,beta-unsaturated ketone moiety seemed to be the pharmacophore required for inhibition of VCAM-1 expression. Compound 19 showed significant antiinflammatory effects in a mouse model of allergic inflammation, indicating that this series of compounds might have therapeutic value for human asthma and other inflammatory disorders. PMID:17323940

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

    PubMed

    Novotny, Laura A; Bakaletz, Lauren O

    2016-08-01

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

  4. Regulation of vascular cell adhesion molecule-1 expression by IL-4 and TNF-alpha in cultured endothelial cells.

    PubMed Central

    Iademarco, M F; Barks, J L; Dean, D C

    1995-01-01

    Interaction between vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells and alpha 4 integrins on leukocytes is thought to mediate the selective recruitment of eosinophils and lymphocytes that occurs in allergic diseases. IL-4 is associated with allergic conditions, and it has been shown to selectively increase expression of VCAM-1 on endothelial cells in vivo, suggesting that it could be responsible for VCAM-1 expression in allergic disease. Using a combination of immunofluorescence, flow cytometry, and Northern analysis, we compared the effect of TNF-alpha and IL-4 on VCAM-1 expression. TNF-alpha is also associated with allergic diseases, and it rapidly increases transcription of the VCAM-1 gene. The effect of IL-4 was relatively modest with prolonged kinetics: VCAM-1 was not detected until 72 h after treatment with IL-4. However, when TNF-alpha and IL-4 were combined, there was a synergistic increase in VCAM-1 expression and a dramatic prolongation of the appearance of VCAM-1 on the cell surface. This synergy results from a combination of transcriptional activation by TNF-alpha and the stabilization of resulting transcripts by IL-4. We propose that IL-4 allows subthreshold concentrations of TNF-alpha (concentrations that would not normally activate expression of adhesion molecules on the endothelium) to selectively increase VCAM-1 expression and to prolong its appearance on the surface of cells in allergic disease. Images PMID:7529260

  5. Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis.

    PubMed

    Zhu, D; Cheng, C F; Pauli, B U

    1992-06-01

    The 90-kD lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) selectively promotes Ca(2+)-dependent adhesion of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, high lung-metastatic B16-F10 melanoma cells bind in significantly higher numbers to Lu-ECAM-1 than their intermediate and low lung-metastatic counterparts B16-L8-F10 and B16-F0, respectively. Maximum attachment is observed at a density of approximately 2.4 x 10(2) Lu-ECAM-1 sites/microns2 of plastic surface. B16 melanoma cell binding to Lu-ECAM-1 is blocked by mAb 6D3 and is competitively inhibited by soluble Lu-ECAM-1. C57B1/6 mice passively immunized with anti-Lu-ECAM-1 mAb 6D3 or actively immunized with purified Lu-ECAM-1 exhibit an anti-Lu-ECAM-1 antibody titer-dependent reduction in the number of B16 experimental metastases. Lu-ECAM-1 promotes neither binding nor metastasis of other lung-metastatic tumor cells (e.g., KLN205). Our data indicate that an "antiadhesion" therapy directed at interfering with the adherence of blood-borne tumor cells to organ-specific vascular endothelium is efficient in the control of metastasis formation in selective organ sites.

  6. Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis.

    PubMed Central

    Zhu, D; Cheng, C F; Pauli, B U

    1992-01-01

    The 90-kD lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) selectively promotes Ca(2+)-dependent adhesion of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, high lung-metastatic B16-F10 melanoma cells bind in significantly higher numbers to Lu-ECAM-1 than their intermediate and low lung-metastatic counterparts B16-L8-F10 and B16-F0, respectively. Maximum attachment is observed at a density of approximately 2.4 x 10(2) Lu-ECAM-1 sites/microns2 of plastic surface. B16 melanoma cell binding to Lu-ECAM-1 is blocked by mAb 6D3 and is competitively inhibited by soluble Lu-ECAM-1. C57B1/6 mice passively immunized with anti-Lu-ECAM-1 mAb 6D3 or actively immunized with purified Lu-ECAM-1 exhibit an anti-Lu-ECAM-1 antibody titer-dependent reduction in the number of B16 experimental metastases. Lu-ECAM-1 promotes neither binding nor metastasis of other lung-metastatic tumor cells (e.g., KLN205). Our data indicate that an "antiadhesion" therapy directed at interfering with the adherence of blood-borne tumor cells to organ-specific vascular endothelium is efficient in the control of metastasis formation in selective organ sites. Images PMID:1601982

  7. Differential regulation of leukocyte function-associated antigen-1/ intercellular adhesion molecules-1-dependent adhesion and aggregation in HL-60 cells.

    PubMed

    Katagiri, K; Kinashi, T; Irie, S; Katagiri, T

    1996-05-15

    Activation of integrin and organization of cytoskeletal proteins are highly regulated in cell adhesion and aggregation. The interaction of leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecules-1 (ICAM-1) mediates cell adhesion and aggregation, which facilitate leukocyte trafficking to inflamed tissues and augment effector functions. We investigated how LFA-1/ICAM-1-mediated adhesion and aggregation are regulated in HL-60 cells induced to differentiate into neutrophils by retinoic acid (RA). Uninduced HL-60 cells did not bind to ICAM-1 even with stimulation by 12-0-tetradecanoyl phorbol-13-acetate, although they express LFA-1 on the cell surface. When cultured with RA for 24 hours, HL-60 cells were able to adhere to ICAM-1 constitutively. The induction of adhesion did not accompany any change in surface density of LFA-1, indicating that the avidity of LFA-1 was increased. The change in its avidity required de novo synthesis of proteins. Although ICAM-1 was intensely expressed on RA-induced HL-60 cells, these cells did not show any cellular aggregation. The HL-60 cells transfected with the active form of Ras (Val12) exhibited LFA-1/ICAM-1-dependent aggregation by RA stimulation without change in the avidity of LFA-1. In these Ras-transfectants, a cytoskeletal protein, paxillin, was tyrosine-phosphorylated, and the level of F-actin increased. Transforming growth factor (TGF) beta, as well as cytochalasin D, prevented both the tyrosine phosphorylation of paxillin and the aggregation without any effects on the avidity of LFA-1. Thus, an increase in the avidity of LFA-1 was not sufficient for the induction of aggregation, which required activation of Ras and reorganization of cytoskeletal proteins. These results suggest that distinct regulatory mechanisms control LFA-1/ICAM-1-dependent adhesion and aggregation in HL-60 cells differentiating into neutrophils.

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

    PubMed Central

    Kanemaru, Kazumasa; Noguchi, Emiko; Tokunaga, Takahiro; Nagai, Kei; Hiroyama, Takashi; Nakamura, Yukio; Tahara-Hanaoka, Satoko; Shibuya, Akira

    2015-01-01

    Mast cell (MC) activation contributes considerably to immune responses, such as host protection and allergy. Cell surface immunoreceptors expressed on MCs play an important role in MC activation. Although various immunoreceptors on MCs have been identified, the regulatory mechanism of MC activation is not fully understood. To understand the regulatory mechanisms of MC activation, we used gene expression analyses of human and mouse MCs to identify a novel immunoreceptor expressed on MCs. We found that Tek, which encodes Tie2, was preferentially expressed in the MCs of both humans and mice. However, Tie2 was not detected on the cell surface of the mouse MCs of the peritoneal cavity, ear skin, or colon lamina propria. In contrast, it was expressed on mouse bone marrow–derived MCs and bone marrow MC progenitors (BM-MCps). Stimulation of Tie2 by its ligand angiopoietin-1 induced tyrosine phosphorylation of Tie2 in MEDMC-BRC6, a mouse embryonic stem cell-derived mast cell line, and enhanced MEDMC-BRC6 and mouse BM-MCp adhesion to vascular cell adhesion molecule-1 (VCAM-1) through α4β1 integrin. These results suggest that Tie2 signaling induces α4β1 integrin activation on BM-MCps for adhesion to VCAM-1. PMID:26659448

  9. An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling.

    PubMed

    Bergom, Carmen; Paddock, Cathy; Gao, Cunji; Holyst, Trudy; Newman, Debra K; Newman, Peter J

    2008-04-15

    The Ig-ITIM family member PECAM-1 is expressed in vascular and endothelial cells, and its functions include suppression of mitochondria-dependent apoptosis. Previous studies have identified distinct PECAM-1 cytoplasmic domain splice variants at the mRNA, but not protein, level. Several relatively abundant mRNA isoforms lack exon 15 (Delta15) and would theoretically encode a protein with a truncated cytoplasmic domain and a unique C-terminal sequence. Using a novel rabbit polyclonal antibody that specifically recognizes Delta15 PECAM-1, we found that the Delta15 PECAM-1 isoform was expressed in human tissues, including brain, testes and ovary. This isoform was also expressed on the cell surface of human platelets, human umbilical vein endothelial cells (HUVECs) and the Jurkat T-cell leukemia, human erythroleukemia (HEL) and U937 histiocytic lymphoma cell lines. Furthermore, murine platelets and lung lysates demonstrated abundant amounts of exon-15-deficient PECAM-1. Functional studies revealed that Delta15 PECAM-1 retains both its homophilic binding capacity and its ability to signal by means of its immunoreceptor tyrosine-based inhibitory motif (ITIM) domains. Delta15 PECAM-1 was unable, however, to protect against apoptosis induced by overexpression of Bax or treatment with the chemotherapy agent etoposide. These studies suggest a novel role for the PECAM-1 C-terminus in cytoprotective signaling and highlight a need for further characterization of expression of PECAM-1 isoforms in normal and malignant tissues. PMID:18388311

  10. IL-18 regulates IL-1β-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1

    PubMed Central

    Vidal-Vanaclocha, Fernando; Fantuzzi, Giamila; Mendoza, Lorea; Fuentes, Angela M.; Anasagasti, Miren J.; Martín, Javier; Carrascal, Teresa; Walsh, Patrick; Reznikov, Leonid L.; Kim, Soo-Hyun; Novick, Daniela; Rubinstein, Menachem; Dinarello, Charles A.

    2000-01-01

    Proinflammatory cytokines, including IL-1β and tumor necrosis factor-α (TNF-α), promote cancer cell adhesion and liver metastases by up-regulating the expression of vascular cell adhesion molecule-1 (VCAM-1) on hepatic sinusoidal endothelium (HSE). In this study, hepatic metastasis after intrasplenically injected mouse B16 melanoma (B16M) cells was reduced 84–95% in mice with null mutations for either IL-1β or the IL-1β-converting enzyme (ICE, caspase-1) compared with wild-type mice. On day 12, 47% of wild-type mice were dead compared with 19% of either IL-1β or ICE-deficient mice. In vitro, conditioned medium from B16M cells (B16M-CM) induced the release of TNF-α and IL-1β from cultures of primary murine HSE. The effect of B16M-CM on HSE resulted in increased numbers of B16M cells adhering to HSE, which was completely abrogated by a specific inhibitor of ICE, anti-IL-18 or IL-18-binding protein. Exogenous IL-18 added to HSE also increased the number of adhering melanoma cells; however, this was not affected by IL-1 receptor blockade or TNF neutralization but rather by anti-VCAM-1. These results demonstrate a role for IL-1β and IL-18 in the development of hepatic metastases of B16M in vivo. In vitro, soluble products from B16M cells stimulate HSE to sequentially release TNF-α, IL-1β, and IL-18. The IL-18 cytokine increases expression of VCAM-1 and the adherence of melanoma cells. PMID:10639148

  11. Expression of E-Selectin, P-Selectin, and Intercellular Adhesion Molecule-1 during Experimental Murine Listeriosis

    PubMed Central

    López, Santiago; Prats, Neus; Marco, Alberto Jesús

    1999-01-01

    The expression of adhesion molecules E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1) was immunohistochemically investigated during the course of experimental murine listeriosis. Infection was monitored by microbiological count of blood, liver, and spleen. After an early generalized expression of P-selectin and ICAM-1, a later regulation occurred specifically to areas of inflammation. Expression of E-selectin was faint and inconstantly detected in all of the studied organs. In the liver, typical lesions of murine listeriosis were related to the expression of ICAM-1 on sinusoidal endothelial cells and the biliary system and to the de novo expression of P-selectin in hepatic portal vessels. Inflammation in the spleen was related to the expression of ICAM-1 on red pulp sinusoidal cells, especially in the marginal sinus. High endothelial venules of inflamed lymph nodes also expressed P-selectin and ICAM-1. Lesions in the central nervous system appeared on day 3 after infection as a pyogranulomatous leptomeningitis associated with an intense expression of P-selectin and ICAM-1 in meningeal vessels, especially those in the hippocampal sulcus, suggesting a way through which inflammation initially reach the central nervous system during experimental murine listeriosis. Leptomeningitis was followed by the presence of ventriculitis, which was related to the up-regulation of ICAM-1 on choroid plexus epithelial cells, periventricular vessels and ependymal cells. Up-regulation of P-selectin and ICAM-1 during experimental murine listeriosis could play an important role in the recruitment of leukocytes, especially to the liver, lymphoid organs, and central nervous system. PMID:10514421

  12. SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects

    PubMed Central

    Deak, Kristen L.; Boyles, Abee L.; Etchevers, Heather C.; Melvin, Elizabeth C.; Siegel, Deborah G.; Graham, Felicia L.; Slifer, Susan H.; Enterline, David S.; George, Timothy M.; Vekemans, Michel; McClay, David; Bassuk, Alexander G.; Kessler, John A.; Linney, Elwood; Gilbert, John R.

    2011-01-01

    Neural tube defects (NTDs) are common birth defects, occurring in approximately 1/1,000 births; both genetic and environmental factors are implicated. To date, no major genetic risk factors have been identified. Throughout development, cell adhesion molecules are strongly implicated in cell–cell interactions, and may play a role in the formation and closure of the neural tube. To evaluate the role of neural cell adhesion molecule 1 (NCAM1) in risk of human NTDs, we screened for novel single-nucleotide polymorphisms (SNPs) within the gene. Eleven SNPs across NCAM1 were genotyped using TaqMan. We utilized a family-based approach to evaluate evidence for association and/or linkage disequilibrium. We evaluated American Caucasian simplex lumbosacral myelomeningocele families (n=132 families) using the family based association test (FBAT) and the pedigree disequilibrium test (PDT). Association analysis revealed a significant association between risk for NTDs and intronic SNP rs2298526 using both the FBAT test (P=0.0018) and the PDT (P=0.0025). Using the HBAT version of the FBAT to look for haplotype association, all pairwise comparisons with SNP rs2298526 were also significant. A replication study set, consisting of 72 additional families showed no significant association; however, the overall trend for overtransmission of the less common allele of SNP rs2298526 remained significant in the combined sample set. In addition, we analyzed the expression pattern of the NCAM1 protein in human embryos, and while NCAM1 is not expressed within the neural tube at the time of closure, it is expressed in the surrounding and later in differentiated neurons of the CNS. These results suggest variations in NCAM1 may influence risk for human NTDs. PMID:15883837

  13. Circulating soluble adhesion molecules in patients with giant cell arteritis. Correlation between soluble intercellular adhesion molecule-1 (sICAM-1) concentrations and disease activity

    PubMed Central

    Coll-Vinent, B.; Vilardell, C.; Font, C.; Oristrell, J.; Hernandez-Rodrigu..., J.; Yague, J.; Urbano-Marquez, A.; Grau, J.; Cid, M.

    1999-01-01

    OBJECTIVE—To evaluate whether changes in concentrations of circulating adhesion molecules are related to disease activity in patients with giant cell arteritis (GCA).
METHODS—A sandwich ELISA was used to measure soluble intercellular adhesion molecule-1 (sICAM-1), sICAM-3, vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and L-selectin (sL-selectin) in serum and plasma samples from patients with GCA. A cross sectional study was performed on 64 GCA patients at different activity stages and on 35 age and sex matched healthy donors. Thirteen of these patients were evaluated at the time of diagnosis and serially during follow up.
RESULTS—At the time of diagnosis, sICAM-1 concentrations were significantly higher in active GCA patients than in controls (mean (SD) 360.55 (129.78) ng/ml versus 243.25 (47.43) ng/ml, p<0.001). In contrast, sICAM-3, sVCAM-1, sE-selectin, and sL-selectin values did not differ from those obtained in normal donors. With corticosteroid administration, a decrease in sICAM-1 concentrations was observed, reaching normal values when clinical remission was achieved (263.18 (92.7) ng/ml globally, 293.59 (108.39) ng/ml in the group of patients in recent remission, and 236.83 (70.02) ng/ml in those in long term remission). In the 13 patients followed up longitudinally, sICAM-1 values also normalised with clinical remission (225.87 (64.25) ng/ml in patients in recent remission, and 256.29 (75.15) ng/ml in those in long term remission).
CONCLUSIONS—Circulating sICAM-1 concentrations clearly correlate with clinically apparent disease activity in GCA patients. Differences with results previously found in patients with other vasculitides may indicate that different pathogenic mechanisms contribute to vascular inflammation in different disorders.

 Keywords: adhesion molecules; giant cell arteritis; inflammation PMID:10364919

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

    PubMed Central

    Grabmaier, U.; Kania, G.; Kreiner, J.; Grabmeier, J.; Uhl, A.; Huber, B. C.; Lackermair, K.; Herbach, N.; Todica, A.; Eriksson, U.; Weckbach, L. T.; Brunner, S.

    2016-01-01

    Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of mice with coxsackie virus-induced as well as in patients with viral infection-triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a biomarker in inflammatory heart diseases remains unclear. Therefore, we investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly correlated with disease activity and progression of cardiac dysfunction in the mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide together with complete Freund`s adjuvant. ELISA revealed strong expression of cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized compared to control mice at acute and chronic stages of the disease. sVCAM-1 did not correlate with the degree of acute cardiac inflammation analyzed by histology or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM. Cardiac systolic dysfunction studied with positron emission tomography indicated a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages of the disease but showed no strong correlation with the severity of EAM. PMID:27501319

  15. Carcinoembryonic antigen-related cell adhesion molecule-1 regulates granulopoiesis by inhibition of granulocyte colony-stimulating factor receptor.

    PubMed

    Pan, Hao; Shively, John E

    2010-10-29

    Although carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is an activation marker for neutrophils and delays neutrophil apoptosis, the role of CEACAM1 in granulopoiesis and neutrophil-dependent host immune responses has not been investigated. CEACAM1 expression correlated with granulocytic differentiation, and Ceacam1(-/-) mice developed neutrophilia because of loss of the Src-homology-phosphatase-1 (SHP-1)-dependent inhibition of granulocyte colony-stimulating factor receptor (G-CSFR) signal transducer and activator of transcription (Stat3) pathway provided by CEACAM1. Moreover, Ceacam1(-/-) mice were hypersensitive to Listeria Monocytogenes (LM) infection with an accelerated mortality. Reintroduction of CEACAM1 into Ceacam1(-/-) bone marrow restored normal granulopoiesis and host sensitivity to LM infection, while mutation of its immunoreceptor tyrosine-based inhibitory motifs (ITIMs) abrogated this restoration. shRNA-mediated reduction of Stat3 amounts rescued normal granulopoiesis, attenuating host sensitivity to LM infection in Ceacam1(-/-) mice. Thus, CEACAM1 acted as a coinhibitory receptor for G-CSFR regulating granulopoiesis and host innate immune response to bacterial infections.

  16. Coxsackievirus A21 binds to decay-accelerating factor but requires intercellular adhesion molecule 1 for cell entry.

    PubMed Central

    Shafren, D R; Dorahy, D J; Ingham, R A; Burns, G F; Barry, R D

    1997-01-01

    It is becoming increasingly apparent that many viruses employ multiple receptor molecules in their cell entry mechanisms. The human enterovirus coxsackievirus A21 (CAV21) has been reported to bind to the N-terminal domain of intercellular adhesion molecule 1 (ICAM-1) and undergo limited replication in ICAM-1-expressing murine L cells. In this study, we show that in addition to binding to ICAM-1, CAV21 binds to the first short consensus repeat (SCR) of decay-accelerating factor (DAF). Dual antibody blockade using both anti-ICAM-1 (domain 1) and anti-DAF (SCR1) monoclonal antibodies (MAbs) is required to completely abolish binding and replication of high-titered CAV21. However, the binding of CAV21 to DAF, unlike that to ICAM-1, does not initiate a productive cell infection. The capacity of an anti-DAF (SCR3) MAb to block CAV21 infection but not binding, coupled with immunoprecipitation data from chemical cross-linking studies, indicates that DAF and ICAM-1 are closely associated on the cell surface. It is therefore suggested that DAF may function as a low-affinity attachment receptor either enhancing viral presentation or providing a viral sequestration site for subsequent high-affinity binding to ICAM-1. PMID:9151867

  17. Discovery of novel phenolic antioxidants as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

    PubMed

    Meng, Charles Q; Somers, Patricia K; Hoong, Lee K; Zheng, X Sharon; Ye, Zhihong; Worsencroft, Kimberly J; Simpson, Jacob E; Hotema, Martha R; Weingarten, M David; MacDOnald, Mathew L; Hill, Russell R; Marino, Elaine M; Suen, Ki-Ling; Luchoomun, Jayraz; Kunsch, Charles; Landers, Laura K; Stefanopoulos, Dimitria; Howard, Randy B; Sundell, Cynthia L; Saxena, Uday; Wasserman, Martin A; Sikorski, James A

    2004-12-01

    Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to endothelial cells and is implicated in many inflammatory conditions. Since part of the signal transduction pathway that regulates the activation of VCAM-1 expression is redox-sensitive, compounds with antioxidant properties may have inhibitory effects on VCAM-1 expression. Novel phenolic compounds have been designed and synthesized starting from probucol (1). Many of these compounds demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expression and displayed potent antioxidant effects in vitro. Some of these derivatives (4o, 4p, 4w, and 4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 from human peripheral blood mononuclear cells (hPBMCs) in a concentration-dependent manner in vitro and showed antiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently in clinical trials for the treatment of rheumatoid arthritis (RA) and prevention of chronic organ transplant rejection, respectively. PMID:15566311

  18. Effects of cytokines and periodontopathic bacteria on the leukocyte function-associated antigen 1/intercellular adhesion molecule 1 pathway in gingival fibroblasts in adult periodontitis.

    PubMed Central

    Hayashi, J; Saito, I; Ishikawa, I; Miyasaka, N

    1994-01-01

    We investigated the effects of inflammatory cytokines and periodontopathic bacteria on expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin (endothelial leukocyte adhesion molecule 1) in cultured human gingival fibroblasts (HGF). Cell surface ICAM-1 was upregulated on HGF under transcriptional control by exposure not only to interleukin-1 beta, tumor necrosis factor alpha, and gamma interferon but also to sonic extracts prepared from Porphyromonas gingivalis and Prevotella intermedia (nigrescens) and lipopolysaccharides from Escherichia coli. However, these stimuli induced only minimal expression of vascular cell adhesion molecule 1 and E-selectin on HGF. Binding assays using HGF and Molt 4, the human T-cell leukemia cell line, showed induced ICAM-1 to be functional, and the increased binding was blocked by a combination of monoclonal antibodies against ICAM-1 and leukocyte function-associated antigen 1. Furthermore, gingival tissues from adult periodontitis patients showed increased mRNA expression of ICAM-1 compared with that in tissues from normal healthy donors. In immunohistological analysis, we also observed in vivo that the expression of ICAM-1 on fibroblasts in adult periodontitis tissues was greater than that in normal gingiva. Thus, the overexpression of ICAM-1 on gingival fibroblasts induced by cytokines and periodontopathic bacteria is speculated to be deeply involved in the accumulation and retention of leukocyte function-associated antigen 1-bearing leukocytes in adult periodontitis lesions. Images PMID:7525481

  19. Effects of cytokines and periodontopathic bacteria on the leukocyte function-associated antigen 1/intercellular adhesion molecule 1 pathway in gingival fibroblasts in adult periodontitis.

    PubMed

    Hayashi, J; Saito, I; Ishikawa, I; Miyasaka, N

    1994-12-01

    We investigated the effects of inflammatory cytokines and periodontopathic bacteria on expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin (endothelial leukocyte adhesion molecule 1) in cultured human gingival fibroblasts (HGF). Cell surface ICAM-1 was upregulated on HGF under transcriptional control by exposure not only to interleukin-1 beta, tumor necrosis factor alpha, and gamma interferon but also to sonic extracts prepared from Porphyromonas gingivalis and Prevotella intermedia (nigrescens) and lipopolysaccharides from Escherichia coli. However, these stimuli induced only minimal expression of vascular cell adhesion molecule 1 and E-selectin on HGF. Binding assays using HGF and Molt 4, the human T-cell leukemia cell line, showed induced ICAM-1 to be functional, and the increased binding was blocked by a combination of monoclonal antibodies against ICAM-1 and leukocyte function-associated antigen 1. Furthermore, gingival tissues from adult periodontitis patients showed increased mRNA expression of ICAM-1 compared with that in tissues from normal healthy donors. In immunohistological analysis, we also observed in vivo that the expression of ICAM-1 on fibroblasts in adult periodontitis tissues was greater than that in normal gingiva. Thus, the overexpression of ICAM-1 on gingival fibroblasts induced by cytokines and periodontopathic bacteria is speculated to be deeply involved in the accumulation and retention of leukocyte function-associated antigen 1-bearing leukocytes in adult periodontitis lesions. PMID:7525481

  20. Endothelial LSP1 Modulates Extravascular Neutrophil Chemotaxis by Regulating Nonhematopoietic Vascular PECAM-1 Expression.

    PubMed

    Hossain, Mokarram; Qadri, Syed M; Xu, Najia; Su, Yang; Cayabyab, Francisco S; Heit, Bryan; Liu, Lixin

    2015-09-01

    During inflammation, leukocyte-endothelial cell interactions generate molecular signals that regulate cell functions. The Ca(2+)- and F-actin-binding leukocyte-specific protein 1 (LSP1) expressed in leukocytes and nonhematopoietic endothelial cells is pivotal in regulating microvascular permeability and leukocyte recruitment. However, cell-specific function of LSP1 during leukocyte recruitment remains elusive. Using intravital microscopy of cremasteric microvasculature of chimeric LSP1-deficient mice, we show that not neutrophil but endothelial LSP1 regulates neutrophil transendothelial migration and extravascular directionality without affecting the speed of neutrophil migration in tissue in response to CXCL2 chemokine gradient. The expression of PECAM-1-sensitive α6β1 integrins on the surface of transmigrated neutrophils was blunted in mice deficient in endothelial LSP1. Functional blocking studies in vivo and in vitro elucidated that α6β1 integrins orchestrated extravascular directionality but not the speed of neutrophil migration. In LSP1-deficient mice, PECAM-1 expression was reduced in endothelial cells, but not in neutrophils. Similarly, LSP1-targeted small interfering RNA silencing in murine endothelial cells mitigated mRNA and protein expression of PECAM-1, but not ICAM-1 or VCAM-1. Overexpression of LSP1 in endothelial cells upregulated PECAM-1 expression. Furthermore, the expression of transcription factor GATA-2 that regulates endothelial PECAM-1 expression was blunted in LSP1-deficient or LSP1-silenced endothelial cells. The present study unravels endothelial LSP1 as a novel cell-specific regulator of integrin α6β1-dependent neutrophil extravascular chemotactic function in vivo, effective through GATA-2-dependent transcriptional regulation of endothelial PECAM-1 expression. PMID:26238489

  1. In situ expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in calves with acute Pasteurella haemolytica pneumonia.

    PubMed

    Radi, Z A; Register, K B; Lee, E K; Kehrli, M E; Brogden, K A; Gallup, J M; Ackermann, M R

    1999-09-01

    The in situ expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in normal and pneumonic lung tissues of Holstein calves with bovine leukocyte adhesion deficiency (BLAD) was compared with that of age-matched non-BLAD Holstein calves by in situ hybridization. Twenty-four Holstein calves (both BLAD and non-BLAD) were randomly assigned to one of two experimental groups and inoculated intrabronchially with Pasteurella haemolytica or pyrogen-free saline. Lung tissues were collected and fixed in 10% neutral formalin at 2 or 4 hours postinoculation (PI). The expression and distribution of ICAM-1 mRNA in the different cell types of the lung tissue was detected by in situ hybridization with a 307-base-pair bovine ICAM-1 riboprobe. In lungs of both non-BLAD and BLAD saline-inoculated calves, ICAM-1 expression was present in epithelial cells but occurred in <30% of cells in bronchi, bronchioles, and alveoli. ICAM-1 expression in vascular endothelial cells was present in <30% of cells in pulmonary arteries and veins. The expression of ICAM-1 was significantly greater (>60% of cells) in bronchiolar and alveolar epithelial cells and pulmonary endothelial cells of arteries and veins in both BLAD and non-BLAD calves inoculated with P. haemolytica. Bronchiolar epithelium had the highest intensity of mRNA expression and highest percentage of cells that were stained, whereas bronchial epithelium had the lowest intensity and percentage of cells stained. Most alveolar macrophages and neutrophils in infected lungs also expressed ICAM-1. ICAM-1 expression was generally increased in infected BLAD calves at 2 hours PI as compared with non-BLAD calves but not at 4 hours PI. The increased expression of ICAM-1 during acute P. haemolytica pneumonia in calves suggests that ICAM-1 is upregulated and may play a role in leukocyte infiltration. The extent of ICAM-1 expression in P. haemolytica-inoculated calves with BLAD was initially enhanced but otherwise similar to that in non

  2. Plasma zinc levels inversely correlate with vascular cell adhesion molecule-1 concentration in children with sickle cell disease.

    PubMed Central

    Kuvibidila, Solo R.; Sandoval, Manuel; Lao, Juan; Velez, Maria; Yu, Lolie; Ode, David; Gardner, Renée; Lane, Gerald; Warrier, Raj P.

    2006-01-01

    Zinc deficiency has been implicated in impaired cell-mediated immunity of children with sickle cell disease (SCD). However, its influence on the expression of vascular cell-adhesion molecule-1 (VCAM-1) on endothelial cells, a protein involved in vasoocclusion, has not been previously investigated. We therefore measured (soluble) sVCAM-1 and zinc in 76 SCD children and 96 non-SCD children, mean age 7.73 years and 11.24 years, respectively. Although mean zinc levels of both groups were within the normal range (approximately 14.5 micromol/l), 14.5 % of SCD and 11% of non-SCD children (without inflammation) had levels below normal (10.7 micromol/L). Mean sVCAM-1 concentrations of SCD children (837 microg/l) were significantly higher than those of controls (627 microg/l) (p < 0.001). Differences persisted after taking into account age, hemoglobin phenotype, and inflammation (alpha-l acid glycoprotein >l g/l and C-reactive protein >10 mg/I). sVCAM-1 negatively correlated with serum (r = -0.444) and red blood cells zinc (r = -0.242, p < 0.05) but not with acute-phase proteins. Mean sVCAM-1 tended to be higher in SCD children with than in those without a history of a health problem (infection, pain crisis or were transfused; not significant). Data suggest that zinc may modulate the clinical status of SCD children through VCAM-1 expression, and zinc supplementation may be beneficial in these patients. PMID:16916123

  3. Prognostic prediction and diagnostic role of intercellular adhesion molecule-1 (ICAM1) expression in clear cell renal cell carcinoma.

    PubMed

    Shi, Xuebing; Jiang, Jifa; Ye, Xiaobing; Liu, Yanyan; Wu, Qiong; Wang, Lu

    2014-08-01

    The intercellular adhesion molecule-1 (ICAM1) has been reported to function in multiple malignancies, but its effect on clear cell renal cell carcinoma (ccRCC) hasn't been discussed yet. This study aimed to identify the potential role of ICAM1 in prognostic prediction and early diagnosis of ccRCC. ICAM1 expression was inspected by immunohistochemistry and correlated with clinicopathologic variables. Association between protein expression and cancer-specific survival (CSS) of ccRCC patients was evaluated and the value of area under the receiver operating characteristics (ROC) curve (AUC) was calculated to measure the protein's diagnostic accuracy. ICAM1 was positively immunostained in 83.2% of 173 ccRCC tissues, but negatively immunostained in all the para-cancerous normal epitheliums of renal tubules. High ICAM1 expression was significantly related to male sex (P = 0.00241), T3/T4 stage (P = 0.02249), non-N0M0 stage (P = 0.03797) and positive renal pelvis invasion (P = 0.04227). Kaplan-Meier survival analysis illustrated that high ICAM1 expression was significantly correlated to a decreased CSS (P = 0.00006). Multivariate Cox analysis indicated that ICAM1 was an independent predictor for CSS of patients (P = 0.00451). Furthermore, the AUC value of ICAM1 in diagnosing ccRCC was 0.916 (P < 0.00001). In conclusion, high ICAM1 expression on tumor cells indicates a poor outcome of patients and ICAM1 is likely to be an independent predictor for the prognosis of ccRCC. Moreover, ICAM1 has a high AUC value and may be a potential and useful diagnostic marker. PMID:24535541

  4. Induction of human macrophage vascular endothelial growth factor and intercellular adhesion molecule-1 by Ureaplasma urealyticum and downregulation by steroids.

    PubMed

    Li, Ying-Hua; Brauner, Annelie; Jensen, Jørgen Skov; Tullus, Kjell

    2002-01-01

    Chronic lung disease (CLD) remains a major cause of morbidity for the prematurely born infant. The pathogenesis of CLD is complex and has not been defined entirely. Infection and lung inflammatory events have been thought to play a key role in the development of CLD. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated and steroids produce some improvement in neonates with this disease. The aim of this study was to investigate if U. urealyticum could stimulate macrophages to produce vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) in vitro, which are potentially associated with both early and later pathological changes in the lung during the development of CLD. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (>/=4 x 10(7) color-changing units/ml) stimulated human macrophages (phorbol 12-myristate 13-acetate-differentiated THP-1 cell line) to produce VEGF and soluble ICAM-1 in a dose-dependent manner (p < 0.05) measured by ELISA. Likewise, cell surface ICAM-1 (CD54) measured by flow cytometry was increased after stimulation with U. urealyticum. This effect was attenuated by budesonide and dexamethasone (p < 0.05). The mRNA expressions of VEGF and ICAM-1 detected by a semi-quantitative reverse transcriptase polymerase chain reaction were also induced in response to U. urealyticum and inhibited by the steroids (p < 0.05). The expression of ICAM-1 was reduced by 85.5% when the TNF-alpha production was neutralized with an anti-TNF-alpha antibody. Our findings imply that U. urealyticum might be involved in the development of CLD of prematurity.

  5. Collaborative Enhancement of Endothelial Targeting of Nanocarriers by Modulating Platelet-Endothelial Cell Adhesion Molecule-1/CD31 Epitope Engagement.

    PubMed

    Chacko, Ann-Marie; Han, Jingyan; Greineder, Colin F; Zern, Blaine J; Mikitsh, John L; Nayak, Madhura; Menon, Divya; Johnston, Ian H; Poncz, Mortimer; Eckmann, David M; Davies, Peter F; Muzykantov, Vladimir R

    2015-07-28

    Nanocarriers (NCs) coated with antibodies (Abs) to extracellular epitopes of the transmembrane glycoprotein PECAM (platelet endothelial cell adhesion molecule-1/CD31) enable targeted drug delivery to vascular endothelial cells. Recent studies revealed that paired Abs directed to adjacent, yet distinct epitopes of PECAM stimulate each other's binding to endothelial cells in vitro and in vivo ("collaborative enhancement"). This phenomenon improves targeting of therapeutic fusion proteins, yet its potential role in targeting multivalent NCs has not been addressed. Herein, we studied the effects of Ab-mediated collaborative enhancement on multivalent NC spheres coated with PECAM Abs (Ab/NC, ∼180 nm diameter). We found that PECAM Abs do mutually enhance endothelial cell binding of Ab/NC coated by paired, but not "self" Ab. In vitro, collaborative enhancement of endothelial binding of Ab/NC by paired Abs is modulated by Ab/NC avidity, epitope selection, and flow. Cell fixation, but not blocking of endocytosis, obliterated collaborative enhancement of Ab/NC binding, indicating that the effect is mediated by molecular reorganization of PECAM molecules in the endothelial plasmalemma. The collaborative enhancement of Ab/NC binding was affirmed in vivo. Intravascular injection of paired Abs enhanced targeting of Ab/NC to pulmonary vasculature in mice by an order of magnitude. This stimulatory effect greatly exceeded enhancement of Ab targeting by paired Abs, indicating that '"collaborative enhancement"' effect is even more pronounced for relatively large multivalent carriers versus free Abs, likely due to more profound consequences of positive alteration of epitope accessibility. This phenomenon provides a potential paradigm for optimizing the endothelial-targeted nanocarrier delivery of therapeutic agents. PMID:26153796

  6. Kinin B1 receptor regulates interactions between neutrophils and endothelial cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion molecule-1.

    PubMed

    Figueroa, Carlos D; Matus, Carola E; Pavicic, Francisca; Sarmiento, Jose; Hidalgo, Maria A; Burgos, Rafael A; Gonzalez, Carlos B; Bhoola, Kanti D; Ehrenfeld, Pamela

    2015-04-01

    Kinins are pro-inflammatory peptides that mimic the cardinal features of inflammation. We examined the concept that expression levels of endothelial intercellular adhesion molecule-1 (ICAM-1) and neutrophil integrins Mac-1 and LFA-1 are modulated by the kinin B1 receptor (B1R) agonist, Lys-des[Arg(9)]bradykinin (LDBK). Stimulation of endothelial cells with LDBK increased the levels of ICAM-1 mRNA transcripts/protein, and also of E-selectin and platelet endothelial adhesion molecule-1. ICAM-1 levels increased in a magnitude comparable with that produced by TNF-α. This stimulatory effect was reduced when endothelial cells, which had been previously transfected with a B1R small interfering RNA, were stimulated with LDBK, under comparable conditions. Similarly, LDBK produced a significant increase in protein levels of LFA-1 and Mac-1 integrins in human neutrophils, an effect that was reversed by pretreatment of cells with 10 µg/ml cycloheximide or a B1R antagonist. Functional experiments performed with post-confluent monolayers of endothelial cells stimulated with LDBK and neutrophils primed with TNF-α, and vice versa, resulted in enhanced adhesiveness between both cells. Neutralizing Abs to ICAM-1 and Mac-1 reduced the adhesion between them. Our results indicate that kinin B1R is a novel modulator that promotes adhesion of leukocytes to endothelial cells, critically enhancing the movement of neutrophils from the circulation to sites of inflammation.

  7. Bone marrow monocyte PECAM-1 deficiency elicits increased osteoclastogenesis resulting in trabecular bone loss.

    PubMed

    Wu, Yue; Tworkoski, Kathryn; Michaud, Michael; Madri, Joseph A

    2009-03-01

    In our investigations of the bone marrow (BM) of PECAM-1 null (knockout, KO) mice, we observed that the trabecular bone volume and number of trabeculae were significantly reduced in femoral and tibial long bones. Further studies in vitro revealed increased numbers and size of osteoclasts, enhanced bone resorption on dentin substrates, and hypersensitivity to macrophage CSF and receptor activator of NF-kappaB ligand in BM-derived osteoclast precursor cultures from KO mice. Associations among PECAM-1, Syk, and SHP-1 were found in wild-type BM monocyte derived osteoclast-like cells. The absence of PECAM-1 and SHP-1 interactions in the KO cells leads to the dysregulation of Syk kinases and/or phosphatases, possibly SHP-1. Indeed, KO derived osteoclast-like cells exhibited increased Syk tyrosine phosphorylation levels compared with WT cells. Lastly, WT mice engrafted with marrow from KO kindred showed loss of trabecular bone analogous to KO mice, consistent with increased osteoclastogenesis. PMID:19234161

  8. TNF-α enhances vascular cell adhesion molecule-1 expression in human bone marrow mesenchymal stem cells via the NF-κB, ERK and JNK signaling pathways

    PubMed Central

    LU, ZI-YUAN; CHEN, WAN-CHENG; LI, YONG-HUA; LI, LI; ZHANG, HANG; PANG, YAN; XIAO, ZHI-FANG; XIAO, HAO-WEN; XIAO, YANG

    2016-01-01

    The migration of circulating mesenchymal stem cells (MSCs) to injured tissue is an important step in tissue regeneration and requires adhesion to the microvascular endothelium. The current study investigated the underlying mechanism of MSC adhesion to endothelial cells during inflammation. In in vitro MSC culture, tumor necrosis factor-α (TNF-α) increased the level of vascular cell adhesion molecule-1 (VCAM-1) expression in a dose-dependent manner. The nuclear factor-κB (NF-κB), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathway inhibitors, pyrrolidine dithiocarbamate (PDTC), U0126 and SP600125, respectively, suppressed VCAM-1 expression induced by TNF-α at the mRNA and protein levels (P<0.05). TNF-α augmented the activation of NF-κB, ERK and JNK, and promoted MSC adhesion to human umbilical vein endothelial cells; however, the inhibitors of NF-κB, ERK and JNK did not affect this process in these cells. The results of the current study indicate that adhesion of circulating MSCs to the endothelium is regulated by TNF-α-induced VCAM-1 expression, which is potentially mediated by the NF-κB, ERK and JNK signaling pathways. PMID:27221006

  9. Breast cancer cells compete with hematopoietic stem and progenitor cells for intercellular adhesion molecule 1-mediated binding to the bone marrow microenvironment.

    PubMed

    Dhawan, Abhishek; Friedrichs, Jens; Bonin, Malte von; Bejestani, Elham Peshali; Werner, Carsten; Wobus, Manja; Chavakis, Triantafyllos; Bornhäuser, Martin

    2016-08-01

    Adhesion-based cellular interactions involved in breast cancer metastasis to the bone marrow remain elusive. We identified that breast cancer cells directly compete with hematopoietic stem and progenitor cells (HSPCs) for retention in the bone marrow microenvironment. To this end, we established two models of competitive cell adhesion-simultaneous and sequential-to study a potential competition for homing to the niche and displacement of the endogenous HSPCs upon invasion by tumor cells. In both models, breast cancer cells but not non-tumorigenic cells competitively reduced adhesion of HSPCs to bone marrow-derived mesenchymal stromal cells (MSCs) in a tumor cell number-dependent manner. Higher adhesive force between breast cancer cells and MSCs, as compared with HSPCs, assessed by quantitative atomic force microscopy-based single-cell force spectroscopy could partially account for tumor cell mediated reduction in HSPC adhesion to MSCs. Genetic inactivation and blockade studies revealed that homophilic interactions between intercellular adhesion molecule 1 (ICAM-1) expressed on tumor cells and MSCs, respectively, regulate the competition between tumor cells and HSPCs for binding to MSCs. Moreover, tumor cell-secreted soluble ICAM-1(sICAM-1) also impaired HSPC adhesion via blocking CD18-ICAM-1 binding between HSPCs and MSCs. Xenotransplantation studies in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice revealed reduction of human HSPCs in the bone marrow via metastatic breast cancer cells. These findings point to a direct competitive interaction between disseminated breast cancer cells and HSPCs within the bone marrow micro environment. This interaction might also have implications on niche-based tumor support. Therefore, targeting this cross talk may represent a novel therapeutic strategy. PMID:27207667

  10. Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action

    SciTech Connect

    Zhang, Haimou; Qin, Gangjian; Liang, Gang; Li, Jinan; Chiu, Isaac; Barrington, Robert A.; Liu, Dongxu . E-mail: dxliu001@yahoo.com

    2007-07-13

    Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-{kappa}B activation and nuclear translocation in an I{kappa}B{alpha}-dependent manner. The inhibitory effects were associated with reduction of inhibitor I{kappa}B kinase activity and stabilization of the NF-{kappa}B inhibitor I{kappa}B. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations.

  11. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    PubMed

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release.

  12. Ligand-induced adhesion to activated endothelium and to vascular cell adhesion molecule-1 in lymphocytes transfected with the N-formyl peptide receptor.

    PubMed

    Honda, S; Campbell, J J; Andrew, D P; Engelhardt, B; Butcher, B A; Warnock, R A; Ye, R D; Butcher, E C

    1994-04-15

    Binding of FMLP to the neutrophil N-formyl peptide receptor (FPR) transmits signals through pertussis toxin-sensitive G proteins triggering Ca2+ flux, superoxide production, granule exocytosis, and neutrophil aggregation and adhesion involving the beta 2 (CD18) integrins. Expression of the FPR in mouse fibroblasts or human kidney cells has been shown to confer an N-formyl peptide-inducible Ca2+ flux in transfectants. Here we demonstrate that the transfected receptor can also support ligand-induced alterations in cellular adhesion. We established stable transfectants of mouse L1-2 pre-B cells with cDNA for human FPR (L1-2 FPR cells). The transfectants bind N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein with 1.4 x 10(5) sites per cell and a dissociation constant of 3.3 nM. Stimulation with FMLP induces a transient Ca2+ flux. FMLP also triggers adhesion of L1-2 FPR cells to TNF-alpha- or LPS-activated bEnd3 cells (mouse brain-derived endothelial cells) and to purified mouse VCAM-1. Binding is inhibited by Abs to VCAM-1 and to the alpha-chain of its lymphocyte receptor (the alpha 4 beta 1 integrin, VLA-4). Stimulation with FMLP does not induce a change in cell surface expression of alpha 4. Induced adhesion to VCAM-1 is rapid, detectable at the earliest times measurable (30 to 60 s after FMLP addition), and is inhibited by pertussis toxin. We conclude that FPR can mediate integrin activation not only in neutrophils but also in lymphocytes, and can trigger rapid adhesion via lymphocyte alpha 4 beta 1. The adhesion of lymphocytes is critical to their migration and targeting; our results suggest the possibility of manipulating adhesive responses through expression of chemoattractant receptors in lymphoid cells engineered for cellular therapy, allowing targeted adhesion and potentially migration in response to locally administered ligands.

  13. Ligand-induced adhesion to activated endothelium and to vascular cell adhesion molecule-1 in lymphocytes transfected with the N-formyl peptide receptor.

    PubMed

    Honda, S; Campbell, J J; Andrew, D P; Engelhardt, B; Butcher, B A; Warnock, R A; Ye, R D; Butcher, E C

    1994-04-15

    Binding of FMLP to the neutrophil N-formyl peptide receptor (FPR) transmits signals through pertussis toxin-sensitive G proteins triggering Ca2+ flux, superoxide production, granule exocytosis, and neutrophil aggregation and adhesion involving the beta 2 (CD18) integrins. Expression of the FPR in mouse fibroblasts or human kidney cells has been shown to confer an N-formyl peptide-inducible Ca2+ flux in transfectants. Here we demonstrate that the transfected receptor can also support ligand-induced alterations in cellular adhesion. We established stable transfectants of mouse L1-2 pre-B cells with cDNA for human FPR (L1-2 FPR cells). The transfectants bind N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein with 1.4 x 10(5) sites per cell and a dissociation constant of 3.3 nM. Stimulation with FMLP induces a transient Ca2+ flux. FMLP also triggers adhesion of L1-2 FPR cells to TNF-alpha- or LPS-activated bEnd3 cells (mouse brain-derived endothelial cells) and to purified mouse VCAM-1. Binding is inhibited by Abs to VCAM-1 and to the alpha-chain of its lymphocyte receptor (the alpha 4 beta 1 integrin, VLA-4). Stimulation with FMLP does not induce a change in cell surface expression of alpha 4. Induced adhesion to VCAM-1 is rapid, detectable at the earliest times measurable (30 to 60 s after FMLP addition), and is inhibited by pertussis toxin. We conclude that FPR can mediate integrin activation not only in neutrophils but also in lymphocytes, and can trigger rapid adhesion via lymphocyte alpha 4 beta 1. The adhesion of lymphocytes is critical to their migration and targeting; our results suggest the possibility of manipulating adhesive responses through expression of chemoattractant receptors in lymphoid cells engineered for cellular therapy, allowing targeted adhesion and potentially migration in response to locally administered ligands. PMID:7511663

  14. Adhesion molecule expression in Graves' thyroid glands; potential relevance of granule membrane protein (GMP-140) and intercellular adhesion molecule-1 (ICAM-1) in the homing and antigen presentation processes.

    PubMed Central

    Miyazaki, A; Mirakian, R; Bottazzo, G F

    1992-01-01

    To assess the potential role of adhesion molecules in the pathogenesis of Graves' disease, we examined the expression of several of these adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1) and granule membrane protein-140 (GMP-140), in sections of Graves' thyroid glands and control thyroids, using immunohistochemical techniques. Up-regulated expression of GMP-140 was frequently observed on endothelial cells (EC) of post-capilliary venules in all Graves' thyroids examined, compared with an occasional weak staining on EC control glands. Some capillary EC around thyroid follicles (perifollicular EC) were strongly positive for GMP-140 in the Graves' thyroids in contrast to a negative staining on the same structures in the control glands. In addition, there was a correlation between the reactivity and frequency of GMP-140 expression on EC and the severity of mononuclear cell (MNC) infiltration in the Graves' thyroids. The expression of ICAM-1 was up-regulated on perifollicular EC and EC of small venules in some thyroids of both Graves' and control groups. Conversely, no significant expression was observed on any type of EC for both endothelial-leucocyte adhesion molecule-1 (ELAM-1) and VCAM-1. However, dendritic-like cells, present within lymphocytic infiltrates, were positive for VCAM-1 in most of the Graves' thyroids examined, especially in those with a severe lymphocytic infiltration. Thyrocytes were constantly negative for the expression of all four adhesion molecules investigated. These data suggest that GMP-140, as well as ICAM-1, could play an important role in the initiation of MNC infiltration in Graves' disease. ELAM-1 and VCAM-1 appear not to be relevant for the migration of MNC from the blood vessels into the target gland, although VCAM-1 expression on dendritic-like cells might play an additively tissue-selective role in autoantigen presentation and subsequent elicitation of autoimmune

  15. Hydrogen peroxide mediates vascular cell adhesion molecule-1 expression from interleukin-18-activated hepatic sinusoidal endothelium: implications for circulating cancer cell arrest in the murine liver.

    PubMed

    Mendoza, L; Carrascal, T; De Luca, M; Fuentes, A M; Salado, C; Blanco, J; Vidal-Vanaclocha, F

    2001-08-01

    The mechanism of intrasinusoidal arrest of circulating cancer cells, which is a critical step in liver metastasis, appears to be facilitated by tumor-derived proinflammatory factors that increase sinusoidal cell adhesion receptors for cancer cells. However, how this prometastatic microenvironment is up-regulated remains unknown. Using intrasplenically injected B16 melanoma (B16M) cells, we show that the expression of vascular cell adhesion molecule-1 (VCAM-1) significantly increased in hepatic sinusoidal endothelium (HSE) cells over physiologic baseline within the first 24 hours of metastatic cancer cell infiltration in the liver. This correlated with increased in vitro adhesion of B16M cells to HSE cells isolated from B16M cell-injected mice. In vivo VCAM-1 blockade with specific antibodies before B16M cell injection decreased sinusoidal retention of luciferase-transfected B16M cells by 85%, and metastasis development by 75%, indicating that VCAM-1 expression on tumor-activated HSE cells had a prometastatic contribution. Because VCAM-1 expression is oxidative stress-inducible, recombinant catalase was in vivo administered, resulting in a complete abrogation of both VCAM-1 expression and B16M cell adhesion increases in HSE cells isolated from B16M cell-injected mice. Catalase also abrogated the proadhesive response of HSE cells to B16M-conditioned medium (B16M-CM) in vitro, although this did not affect the concomitant release of major proinflammatory cytokines by HSE cells. HSE cells treated with B16M-CM released interleukin (IL)-18 via tumor necrosis factor-alpha (TNF-alpha)-dependent IL-1beta in vitro. In turn, H(2)O(2) production from B16M-CM-treated HSE cells was regulated by IL-18. Thus, liver-infiltrating B16M cells activated their adhesion to HSE through a sequential process involving TNF-alpha-dependent IL-1beta, which induced IL-18 to up-regulate VCAM-1 via H(2)O(2). The pivotal position of H(2)O(2) was further supported by the fact that incubation of HSE

  16. Artemether Combined with shRNA Interference of Vascular Cell Adhesion Molecule-1 Significantly Inhibited the Malignant Biological Behavior of Human Glioma Cells

    PubMed Central

    Wang, Ping; Xue, Yi-Xue; Yao, Yi-Long; Yu, Bo; Liu, Yun-Hui

    2013-01-01

    Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma cells were treated with artemether at various concentrations and shRNA interfering technology was employed to silence the expression of VCAM-1. Cell viability, migration, invasiveness and apoptosis were assessed with MTT, wound healing, Transwell and Annexin V-FITC/PI staining. The expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and phosphorylated Akt (p-Akt) was checked by Western blot assay. Results showed that artemether and shRNA-VCAM-1 not only significantly inhibited the migration, invasiveness and expression of MMP-2/9 and p-Akt, but also promoted the apoptosis of U87 cells. Combined treatment of both displayed the maximum inhibitory effects on the malignant biological behavior of glioma cells. Our work revealed the potential therapeutic effects of artemether and antiVCAM-1 in the treatments of gliomas. PMID:23593320

  17. Modulation of tight junction barrier function by outer membrane proteins of enteropathogenic Escherichia coli: role of F-actin and junctional adhesion molecule-1.

    PubMed

    Puthenedam, Manjula; Williams, Peter H; Lakshmi, B S; Balakrishnan, Arun

    2007-08-01

    Enteropathogenic Escherichia coli (EPEC) is a major cause of infantile diarrhea. In this work we investigated the effect of outer membrane proteins (OMP) of EPEC on barrier integrity and the role of actin, junctional adhesion molecule (JAM) and signaling pathways contributing to these changes. Barrier function was assessed by transepithelial electrical resistance (TER). OMP of wild type EPEC, eaeA and maltoporin mutants decreased TER levels of Caco-2 cells. The OMP of espB mutant was deficient in decreasing TER of Caco-2 cells. The proteinase K-digested wild type OMP and EAF mutant OMP did not cause any change in barrier function. Our previous studies have demonstrated that EPEC OMP induced changes in cadherin junctions of Caco-2 cells. Immunofluorescence revealed disruption in actin cytoskeleton by EPEC OMP. However, no change in expression of junctional adhesion molecule-1 was observed. NF-kappaB inhibitor slightly blocked the decrease in TER and protected against actin disruption while ERK1/2 inhibitor had no effect in blocking these changes. In conclusion, our data suggest that the OMP of EPEC alter intestinal barrier function by disrupting actin cytoskeleton and signaling pathways like NF-kappaB may have a role in regulating barrier changes.

  18. FRET Based Quantification and Screening Technology Platform for the Interactions of Leukocyte Function-Associated Antigen-1 (LFA-1) with InterCellular Adhesion Molecule-1 (ICAM-1)

    PubMed Central

    Chakraborty, Sandeep; Núñez, David; Hu, Shih-Yang; Domingo, María Pilar; Pardo, Julian; Karmenyan, Artashes; Chiou, Arthur

    2014-01-01

    The interaction between leukocyte function-associated antigen-1(LFA-1) and intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in cellular adhesion including the extravasation and inflammatory response of leukocytes, and also in the formation of immunological synapse. However, irregular expressions of LFA-1 or ICAM-1 or both may lead to autoimmune diseases, metastasis cancer, etc. Thus, the LFA-1/ICAM-1 interaction may serve as a potential therapeutic target for the treatment of these diseases. Here, we developed one simple ‘in solution’ steady state fluorescence resonance energy transfer (FRET) technique to obtain the dissociation constant (Kd) of the interaction between LFA-1 and ICAM-1. Moreover, we developed the assay into a screening platform to identify peptides and small molecules that inhibit the LFA-1/ICAM-1 interaction. For the FRET pair, we used Alexa Fluor 488-LFA-1 conjugate as donor and Alexa Fluor 555-human recombinant ICAM-1 (D1-D2-Fc) as acceptor. From our quantitative FRET analysis, the Kd between LFA-1 and D1-D2-Fc was determined to be 17.93±1.34 nM. Both the Kd determination and screening assay were performed in a 96-well plate platform, providing the opportunity to develop it into a high-throughput assay. This is the first reported work which applies FRET based technique to determine Kd as well as classifying inhibitors of the LFA-1/ICAM-1 interaction. PMID:25032811

  19. Interleukin-1 alpha produced by human T-cell leukaemia virus type I-infected T cells induces intercellular adhesion molecule-1 expression on lung epithelial cells.

    PubMed

    Nakayama, Yuko; Ishikawa, Chie; Tamaki, Kazumi; Senba, Masachika; Fujita, Jiro; Mori, Naoki

    2011-12-01

    The pathogenic mechanism of human T-cell leukaemia virus type I (HTLV-I)-related pulmonary disease, which involves overexpression of intercellular adhesion molecule-1 (ICAM-1) in lung epithelial cells, was investigated. The supernatant of HTLV-I-infected Tax(+) MT-2 and C5/MJ cells induced ICAM-1 expression on A549 cells, a human tumour cell line with the properties of alveolar epithelial cells. Neutralization of ICAM-1 partially inhibited HTLV-I-infected T-cell adhesion to A549 cells. Analysis of the ICAM-1 promoter showed that the nuclear factor-kappa B-binding site was important for supernatant-induced ICAM-1 expression. Induction of interleukin (IL)-1 alpha (IL-1α) expression in MT-2 and C5/MJ cells was observed compared with uninfected controls and HTLV-I-infected Tax-negative cell lines. The significance of IL-1α as a soluble messenger was supported by blocking the biological activities of MT-2 supernatant with an IL-1α-neutralizing mAb. Moreover, Tax and IL-1α expression was demonstrated in the bronchoalveolar lavage cells of patients with HTLV-I-related pulmonary disease. Immunohistochemistry confirmed ICAM-1 and IL-1α expression in lung epithelial cells and lymphocytes of patients with HTLV-I-related pulmonary diseases, and in a transgenic mouse model of Tax expression. These results suggest that IL-1α produced by HTLV-I-infected Tax(+) T cells is crucial for ICAM-1 expression in lung epithelial cells and subsequent adhesion of lymphocytes in HTLV-I-related pulmonary diseases.

  20. Induction of intercellular adhesion molecule-1 on human brain endothelial cells by HIV-1 gp120: role of CD4 and chemokine coreceptors.

    PubMed

    Stins, Monique F; Pearce, Donna; Di Cello, Francescopaolo; Erdreich-Epstein, Anat; Pardo, Carlos A; Sik Kim, Kwang

    2003-12-01

    Central nervous system dysfunction is commonly observed in children with HIV-1 infection, but the mechanisms whereby HIV-1 causes encephalopathy are not completely understood. We have previously shown that human brain microvascular endothelial cells (HBMEC) from children are responsive to gp120 derived from X4 HIV-1 by increasing expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1. However, the mechanisms involved in gp120-mediated up-regulation of cell adhesion molecule expression is unclear. In the present study, we found that gp120 derived from both X4 and R5 HIV-1 induced increased expression of ICAM-1 on HBMEC, but the degree of this up-regulation differed among the various HBMEC isolates. The up-regulation of ICAM-1 was inhibited by anti-CD4 antibodies as well as by specific antibodies directed against chemokine receptors and small-molecule coreceptor inhibitors. Anti-CD4 antibodies inhibited the increase in ICAM-1 expression mediated by gp120 derived from X4 and R5 HIV-1, whereas antibodies against chemokine receptors displayed a differential inhibition depending on the source of gp120. Both X4 and R5 gp120-induced ICAM-1 expression was sensitive to pertussis toxin and involved the nuclear factor-kB pathway. These findings indicate a direct involvement of CD4 and a differential involvement of chemokine receptors in the activation of pediatric HBMEC by X4 and R5 gp120. The activation of brain endothelium of children by HIV-1 protein gp120 by way of CD4 and chemokine receptors may have implications for the pathogenesis of HIV-1 encephalopathy in the pediatric population.

  1. Simple modifications to Methimazole that enhance its inhibitory effect on Tumor Necrosis Factor-α-induced Vascular Cell Adhesion Molecule-1 expression by human endothelial cells

    PubMed Central

    Alapati, Anuja; Deosarkar, Sudhir P.; Lanier, Olivia L.; Qi, Chunyan; Carlson, Grady E.; Burdick, Monica M.; Schwartz, Frank L.; McCall, Kelly D.; Bergmeier, Stephen C.; Goetz, Douglas J.

    2015-01-01

    The expression of vascular cell adhesion molecule-1 (VCAM-1) on the vascular endothelium can be increased by pro-inflammatory cytokines [e.g. tumor necrosis factor – α (TNF-α)]. VCAM-1 contributes to leukocyte adhesion to, and emigration from, the vasculature which is a key aspect of pathological inflammation. As such, a promising therapeutic approach for pathological inflammation is to inhibit the expression of VCAM-1. Methimazole [3-methyl-1, 3 imidazole-2 thione (MMI)] is routinely used for the treatment of Graves’ disease and patients treated with MMI have decreased levels of circulating VCAM-1. In this study we used cultured human umbilical vein endothelial cells (HUVEC) to investigate the effect of MMI structural modifications on TNF-α induced VCAM-1 expression. We found that addition of a phenyl ring at the 4-nitrogen of MMI yields a compound that is significantly more potent than MMI at inhibiting 24 h TNF-α-induced VCAM-1 protein expression. Addition of a para methoxy to the appended phenyl group increases the inhibition while substitution of a thiazole ring for an imidazole ring in the phenyl derivatives yields no clear difference in inhibition. Addition of the phenyl ring to MMI appears to increase toxicity as does substitution of a thiazole ring for an imidazole ring in the phenyl MMI derivatives. Each of the compounds reduced TNF-α-induced VCAM-1 mRNA expression and had a functional inhibitory effect, i.e. each inhibited monocytic cell adhesion to 24 h TNF-α-activated HUVEC under fluid flow conditions. Combined, these studies provide important insights into the design of MMI-related anti-inflammatory compounds. PMID:25641748

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

    PubMed Central

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

    2016-01-01

    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. PMID:27446295

  3. Increased plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell molecule-1 (sVCAM-1) associated with disease severity in a primate model for severe human malaria: Plasmodium coatneyi-Infected Japanese macaques (Macaca fuscata).

    PubMed

    Kawai, Satoru; Matsumoto, Jun; Aikawa, Masamichi; Matsuda, Hajime

    2003-05-01

    In the present study, we investigated plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in seven Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi. Concentrations of sICAM-1 and sVCAM-1 were significantly elevated in the severe phase; the levels were maximally increased up to six times and three times those before infection, respectively. We subsequently examined kinetic profiles of sICAM-1 and sVCAM-1 concentration in plasma obtained from two infected monkeys. Both infected monkeys had markedly increased levels of these adhesion molecules when they exhibited severe clinical signs correlated with rapid increase in parasitemia. These results suggest that the elevation of levels of sICAM-1 and sVCAM-1 is a critical step in the pathogenesis of severe malaria in vivo.

  4. Modulation of human leukocyte antigen and intracellular adhesion molecule-1 surface expression in malignant and nonmalignant human thyroid cells by cytokines in the context of extracellular matrix.

    PubMed

    Miller, A; Kraiem, Z; Sobel, E; Lider, O; Lahat, N

    2000-11-01

    Interactions between malignant cells and their environment are achieved via cell-surface receptors and adhesion molecules. The extracellular matrix (ECM) and ECM-bound cytokines modulate the expression of cell-surface molecules on target malignant cells, which may lead to changes in their susceptibility to cytolysis, in their ability to present antigens, and in the induction of local immune-cell activation and patrol. Eventually, these alterations may culminate in either the destruction, or escape and proliferation, of the tumor. We studied the effects of the ECM and its components in a "naive" form or following binding of the inflammatory cytokines interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) on the surface expression of human leukocyte antigen (HLA) class-I, HLA class-II (HLA-DR), and intracellular adhesion molecule-1 (ICAM-1), on nonmalignant and malignant thyroid cells. The basal expression of HLA class-I molecules was not significantly changed either by naive ECM and its components or by ECM-bound cytokines. ECM synergized with IFNgamma and TNFalpha in inducing HLA-DR molecules on nonmalignant and malignant thyrocytes, with higher HLA-DR levels on the malignant cells. The laminin component, in particular, synergized with IFNgamma. Basal ICAM-1 expression on nonneoplastic cells was not significantly affected by the cytokines when grown in the absence of ECM, but was significantly upregulated when cells were cultured on ECM. In contrast, in malignant thyrocyte cultures, ECM significantly attenuated IFNgamma- and TNFalpha-mediated enhancement of ICAM-1 expression. We concluded that signals derived from ECM-embedded cytokines participate in the regulation of key thyroid cell surface molecules and, thus, may affect the final outcome of human thyroid malignancies. PMID:11128721

  5. The Interaction Affinity between Vascular Cell Adhesion Molecule-1 (VCAM-1) and Very Late Antigen-4 (VLA-4) Analyzed by Quantitative FRET

    PubMed Central

    Wu, Shu-Han; Karmenyan, Artashes; Chiou, Arthur

    2015-01-01

    Very late antigen-4 (VLA-4), a member of integrin superfamily, interacts with its major counter ligand vascular cell adhesion molecule-1 (VCAM-1) and plays an important role in leukocyte adhesion to vascular endothelium and immunological synapse formation. However, irregular expressions of these proteins may also lead to several autoimmune diseases and metastasis cancer. Thus, quantifying the interaction affinity of the VCAM-1/VLA-4 interaction is of fundamental importance in further understanding the nature of this interaction and drug discovery. In this study, we report an ‘in solution’ steady state organic fluorophore based quantitative fluorescence resonance energy transfer (FRET) assay to quantify this interaction in terms of the dissociation constant (Kd). We have used, in our FRET assay, the Alexa Fluor 488-VLA-4 conjugate as the donor, and Alexa Fluor 546-VCAM-1 as the acceptor. From the FRET signal analysis, Kd of this interaction was determined to be 41.82 ± 2.36 nM. To further confirm our estimation, we have employed surface plasmon resonance (SPR) technique to obtain Kd = 39.60 ± 1.78 nM, which is in good agreement with the result obtained by FRET. This is the first reported work which applies organic fluorophore based ‘in solution’ simple quantitative FRET assay to obtain the dissociation constant of the VCAM-1/VLA-4 interaction, and is also the first quantification of this interaction. Moreover, the value of Kd can serve as an indicator of abnormal protein-protein interactions; hence, this assay can potentially be further developed into a drug screening platform of VLA-4/VCAM-1 as well as other protein-ligand interactions. PMID:25793408

  6. Interaction of actin with carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) receptor in liposomes is Ca2+- and phospholipid-dependent.

    PubMed

    Lu, Rongze; Niesen, Michiel J M; Hu, Weidong; Vaidehi, Nagarajan; Shively, John E

    2011-08-01

    The regulation of binding of G-actin to cytoplasmic domains of cell surface receptors is a common mechanism to control diverse biological processes. To model the regulation of G-actin binding to a cell surface receptor we used the cell-cell adhesion molecule carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1-S) in which G-actin binds to its short cytoplasmic domain (12 amino acids; Chen, C. J., Kirshner, J., Sherman, M. A., Hu, W., Nguyen, T., and Shively, J. E. (2007) J. Biol. Chem. 282, 5749-5760). A liposome model system demonstrates that G-actin binds to the cytosolic domain peptide of CEACAM1-S in the presence of negatively charged palmitoyl-oleoyl phosphatidylserine (POPS) liposomes and Ca(2+). In contrast, no binding of G-actin was observed in palmitoyl-oleoyl phosphatidylcholine (POPC) liposomes or when a key residue in the peptide, Phe-454, is replaced with Ala. Molecular Dynamics simulations on CEACAM1-S in an asymmetric phospholipid bilayer show migration of Ca(2+) ions to the lipid leaflet containing POPS and reveal two conformations for Phe-454 explaining the reversible availability of this residue for G-actin binding. NMR transverse relaxation optimized spectroscopic analysis of (13)C-labeled Phe-454 CEACAM1-S peptide in liposomes plus actin further confirmed the existence of two peptide conformers and the Ca(2+) dependence of actin binding. These findings explain how a receptor with a short cytoplasmic domain can recruit a cytosolic protein in a phospholipid and Ca(2+)-specific manner. In addition, this model system provides a powerful approach that can be applied to study other membrane protein interactions with their cytosolic targets.

  7. Carcinoembryonic antigen-related cell adhesion molecule 1 negatively regulates granulocyte colony-stimulating factor production by breast tumor-associated macrophages that mediate tumor angiogenesis.

    PubMed

    Samineni, Sridhar; Zhang, Zhifang; Shively, John E

    2013-07-15

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a cell adhesion molecule expressed on epithelial cells and activated immune cells, is downregulated in many cancers and plays a role in inhibition of inflammation in part by inhibition of granulocyte colony-stimulating factor (G-CSF) production by myeloid cells. As macrophages are associated with a poor prognosis in breast cancer, but play important roles in normal breast, we hypothesized that CEACAM1 downregulation would lead to tumor promotion under inflammatory conditions. Cocultures of proinflammatory M1 macrophages with CEACAM1 negative MCF7 breast cells produced high levels of G-CSF (10 ng/mL) compared to CEACAM1-transfected MCF7/4S cells (1 ng/mL) or anti-inflammatory M2 macrophage cocultures (0.5 or 0.1 ng/mL, MCF7 or MCF7/4S, respectively). The expression of CEACAM1 on M1s was much greater than for M2s and was observed only in cocultures with either MCF7 or MCF7/4S cells. When M1 macrophages were mixed with MCF7 cells and implanted in murine mammary fat pads of nonobese diabetic/severe combined immunodeficient mice, tumor size and blood vessel density were significantly greater than MCF7 or MCF7/4S only tumors which were hardly detected after 8 weeks of growth. In contrast, M1 cells had a much reduced effect on MCF7/4S tumor growth and blood vessel density, indicating that the tumor inhibitory effect of CEACAM1 is most likely related to its anti-inflammatory action on inflammatory macrophages. These results support our previous finding that CEACAM1 inhibits both G-CSF production by myeloid cells and G-CSF-stimulated tumor angiogenesis.

  8. The P2Y2 nucleotide receptor mediates UTP-induced vascular cell adhesion molecule-1 expression in coronary artery endothelial cells.

    PubMed

    Seye, Cheikh I; Yu, Ningpu; Jain, Renu; Kong, Qiongman; Minor, Tess; Newton, Jessica; Erb, Laurie; González, Fernando A; Weisman, Gary A

    2003-07-01

    P2Y2 receptor up-regulation and activation induces intimal hyperplasia and monocyte/macrophage infiltration in the collared rabbit carotid artery model of vascular injury, suggesting a potential role for P2Y2 receptors in monocyte recruitment by vascular endothelium. In this study, we addressed the hypothesis that activation of P2Y2 receptors by extracellular nucleotides modulates the expression of adhesion molecules on vascular endothelial cells that are important for monocyte recruitment. Results indicated that the equipotent P2Y2 receptor agonists UTP or ATP (1-100 microm) stimulated the expression of vascular cell adhesion molecule-1 (VCAM-1) in human coronary artery endothelial cells (HCAEC) in a time- and dose-dependent manner. P2Y2 antisense oligonucleotides inhibited VCAM-1 expression induced by UTP but not by tumor necrosis factor-alpha. Furthermore, UTP induced VCAM-1 expression in human 1321N1 astrocytoma cell transfectants expressing the recombinant P2Y2 receptor, whereas vector-transfected control cells did not respond to UTP. The effect of UTP on VCAM-1 expression in HCAEC was prevented by depletion of intracellular calcium stores with thapsigargin or by inhibition of p38 mitogen-activated protein kinase or Rho kinase, but was not affected by inhibitors of the mitogen-activated protein/extracellular signal-regulated kinase pathway (i.e. MEK1/2). Consistent with a role for VCAM-1 in the recruitment of monocytes, UTP or ATP increased the adherence of monocytic U937 cells to HCAEC, an effect that was inhibited by anti-VCAM-1 antibodies. These findings suggest a novel role for the P2Y2 receptor in the p38- and Rho kinase-dependent expression of VCAM-1 that mediates the recruitment of monocytes by vascular endothelium associated with the development of atherosclerosis.

  9. EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells

    PubMed Central

    Leng, Weiling; Lei, Xiaotian; Meng, Hao; Ouyang, Xinshou; Liang, Ziwen

    2015-01-01

    Our research group firstly discovered endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number AY074889) as a lipopolysaccharide (LPS) responsive gene in ECV304 cells. The previous studies have further demonstrated the association of EOLA1 with metallothionein 2A (MT2A), while the role of EOLA1 during LPS-induced inflammatory response in ECV304 cells is unknown. In this report, we determined the subcellular localization of EOLA1 and the regulatory capacity of EOLA1 on vascular cell adhesion molecule-1 (VCAM-1) in response to LPS in ECV304 cells. Our results show that EOLA1 is broadly diffuse in the cells, and EOLA1 expression is dramatically induced by LPS. EOLA1 knockdown results in significant enhancement of LPS-induced VCAM-1 production. Consistent with this, overexpression of EOLA1 leads to the reduction of LPS-induced VCAM-1 production. Furthermore, MT2A knockdown reduces LPS-induced VCAM-1 production. Collectively, our results demonstrate a negative regulatory role of EOLA1 on LPS-induced VCAM-1 expression involving its association with MT2A in ECV304 cells. PMID:26881174

  10. Acquired and congenital cholesteatoma: determination of tumor necrosis factor-alpha, intercellular adhesion molecule-1, interleukin-1-alpha and lymphocyte functional antigen-1 in the inflammatory process.

    PubMed

    Akimoto, R; Pawankar, R; Yagi, T; Baba, S

    2000-01-01

    The molecular and cellular factors resulting in the pathologic features of acquired and congenital cholesteatomas are not completely known. Recently, proinflammatory cytokines like interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) have been shown to induce bone resorption, in vitro. To elucidate the key molecules involved in bone resorption and cell infiltration associated with cholesteatoma, we examined the in vivo levels of IL-1 alpha and TNF-alpha, intercellular adhesion molecule-1 (ICAM-1) and lymphocyte functional antigen-1 (LFA-1) in acquired and congenital cholesteatomas, by reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ELISA. Increased levels of IL-1 and TNF-alpha were detected in both types of cholesteatomas as compared to normal skin. Increased ICAM-1 expression and LFA-1+ cells were detected in acquired but not congenital cholesteatoma. Strong correlation was detected between TNF-alpha and bone resorption in both types of cholesteatoma, and between TNF-alpha and ICAM, TNF-alpha and severity of infection, or cell infiltration in acquired cholesteatoma. No correlation existed between various parameters and IL-1 alpha. These results suggest that TNF-alpha may play a crucial role in the pathogenesis of both acquired and congenital cholesteatomas by regulating bone resorption and cell infiltration.

  11. Human Peripheral Blood Eosinophils Express a Functional c-kit Receptor for Stem Cell Factor that Stimulates Very Late Antigen 4 (VLA-4)–mediated Cell Adhesion to Fibronectin and Vascular Cell Adhesion Molecule 1 (VCAM-1)

    PubMed Central

    Yuan, Qian; Austen, K. Frank; Friend, Daniel S.; Heidtman, Matthew; Boyce, Joshua A.

    1997-01-01

    We evaluated mature peripheral blood eosinophils for their expression of the surface tyrosine kinase, c-kit, the receptor for the stromal cell–derived cytokine, stem cell factor (SCF). Cytofluorographic analysis revealed that c-kit was expressed on the purified peripheral blood eosinophils from 8 of 8 donors (4 nonatopic and 4 atopic) (mean channel fluorescence intensity 2.0– 3.6-fold, average 2.8 ± 0.6-fold, greater than the negative control). The uniform and selective expression of c-kit by eosinophils was confirmed by immunohistochemical analysis of peripheral blood buffy coats. The functional integrity of c-kit was demonstrated by the capacity of 100 ng/ml (5 nM) of recombinant human (rh) SCF to increase eosinophil adhesion to 3, 10, and 30 μg/ml of immobilized FN40, a 40-kD chymotryptic fragment of plasma fibronectin, in 15 min by 7.7 ± 1.4-, 5.3 ± 3.3-, and 5.4 ± 0.2-fold, respectively, and their adhesion to 0.1, 0.5, and 1.0 μg/ml vascular cell adhesion molecule-1 (VCAM-1), by 12.7 ± 9.2-, 3.8 ± 2.5-, and 1.7 ± 0.6-fold, respectively. The SCF-stimulated adhesion occurred without concomitant changes in surface integrin expression, thereby indicating an avidity-based mechanism. rhSCF (100 ng/ml, 5 nM) was comparable to rh eotaxin (200 ng/ml, 24 nM) in stimulating adhesion. Cell adhesion to FN40 was completely inhibited with antibodies against the α4 and β1 integrin subunits, revealing that the SCF/c-kit adhesion effect was mediated by a single integrin heterodimer, very late antigen 4 (VLA-4). Thus, SCF represents a newly recognized stromal ligand for the activation of eosinophils for VLA-4–mediated adhesion, which could contribute to the exit of these cells from the blood, their tissue localization, and their prominence in inflammatory lesions. PMID:9221761

  12. Interleukin-8 and Intercellular Adhesion Molecule 1 Regulation in Oral Epithelial Cells by Selected Periodontal Bacteria: Multiple Effects of Porphyromonas gingivalis via Antagonistic Mechanisms

    PubMed Central

    Huang, George T.-J.; Kim, Daniel; Lee, Jonathan K.-H.; Kuramitsu, Howard K.; Haake, Susan Kinder

    2001-01-01

    Interaction of bacteria with mucosal surfaces can modulate the production of proinflammatory cytokines and adhesion molecules produced by epithelial cells. Previously, we showed that expression of interleukin-8 (IL-8) and intercellular adhesion molecule 1 (ICAM-1) by gingival epithelial cells increases following interaction with several putative periodontal pathogens. In contrast, expression of IL-8 and ICAM-1 is reduced after Porphyromonas gingivalis ATCC 33277 challenge. In the present study, we investigated the mechanisms that govern the regulation of these two molecules in bacterially infected gingival epithelial cells. Experimental approaches included bacterial stimulation of gingival epithelial cells by either a brief challenge (1.5 to 2 h) or a continuous coculture throughout the incubation period. The kinetics of IL-8 and ICAM-1 expression following brief challenge were such that (i) secretion of IL-8 by gingival epithelial cells reached its peak 2 h following Fusobacterium nucleatum infection whereas it rapidly decreased within 2 h after P. gingivalis infection and remained decreased up to 30 h and (ii) IL-8 and ICAM-1 mRNA levels were up-regulated rapidly 2 to 4 h postinfection and then decreased to basal levels 8 to 20 h after infection with either Actinobacillus actinomycetemcomitans, F. nucleatum, or P. gingivalis. Attenuation of IL-8 secretion was facilitated by adherent P. gingivalis strains. The IL-8 secreted from epithelial cells after F. nucleatum stimulation could be down-regulated by subsequent infection with P. gingivalis or its culture supernatant. Although these results suggested that IL-8 attenuation at the protein level might be associated with P. gingivalis proteases, the Arg- and Lys-gingipain proteases did not appear to be solely responsible for IL-8 attenuation. In addition, while P. gingivalis up-regulated IL-8 mRNA expression, this effect was overridden when the bacteria were continuously cocultured with the epithelial cells. The IL-8

  13. Cyclic stretching of mesangial cells up-regulates intercellular adhesion molecule-1 and leukocyte adherence: a possible new mechanism for glomerulosclerosis.

    PubMed

    Riser, B L; Varani, J; Cortes, P; Yee, J; Dame, M; Sharba, A K

    2001-01-01

    Intraglomerular hypertension is a primary causal factor in the progressive glomerulosclerosis that characterizes diabetic nephropathy or severe renal ablation. However, inflammation of the glomerular mesangium also participates in at least the early phase of these diseases. In glomerulonephritis, where inflammation is thought to be the predominant causal factor, intraglomerular hypertension is also often present. Mesangial cells (MCs) are critical in orchestrating key functions of the glomerulus including extracellular matrix metabolism, cytokine production, and interaction with leukocytes. Because MCs are subject to increased stretching when intraglomerular hypertension is present, and in glomerulonephritis MC/leukocyte interactions seem to be mediated primarily via the up-regulation of intercellular adhesion molecule-1 (ICAM-1), we examine the possibility that cyclic stretching is a stimulus for increased MC ICAM-1 activity. We demonstrate that the normal low levels of MC ICAM-1 mRNA and protein are dramatically up-regulated by even short intervals of cyclic stretch. This effect is dose- and time-dependent, and requires little amplitude and a brief period of elongation for significant induction. Stretch-induced MC ICAM-1 also leads to a marked elevation in phagocytic leukocyte adherence. This stimulated adherence is equal or greater than that induced by the inflammatory cytokine tumor necrosis factor-alpha, whereas an additive effect occurs when both are applied in combination. Our results indicate that stretch-induced ICAM-1 may provide a direct link between hypertension and inflammation in the progression of injury and glomerulosclerosis in diabetes, renal ablation, and other forms of glomerulonephritis. PMID:11141473

  14. Intercellular adhesion molecule-1 inhibits osteogenic differentiation of mesenchymal stem cells and impairs bio-scaffold-mediated bone regeneration in vivo.

    PubMed

    Xu, Fen-Fen; Zhu, Heng; Li, Xi-Mei; Yang, Fei; Chen, Ji-De; Tang, Bo; Sun, Hong-Guang; Chu, Ya-Nan; Zheng, Rong-Xiu; Liu, Yuan-Lin; Wang, Li-Sheng; Zhang, Yi

    2014-10-01

    Mesenchymal stem cell (MSC) loaded bio-scaffold transplantation is a promising therapeutic approach for bone regeneration and repair. However, growing evidence shows that pro-inflammatory mediators from injured tissues suppress osteogenic differentiation and impair bone formation. To improve MSC-based bone regeneration, it is important to understand the mechanism of inflammation mediated osteogenic suppression. In the present study, we found that synovial fluid from rheumatoid arthritis patients and pro-inflammatory cytokines including interleukin-1α, interleukin-1β, and tumor necrosis factor α, stimulated intercellular adhesion molecule-1(ICAM-1) expression and impaired osteogenic differentiation of MSCs. Interestingly, overexpression of ICAM-1 in MSCs using a genetic approach also inhibited osteogenesis. In contrast, ICAM-1 knockdown significantly reversed the osteogenic suppression. In addition, after transplanting a traceable MSC-poly(lactic-co-glycolic acid) construct in rat calvarial defects, we found that ICAM-1 suppressed MSC osteogenic differentiation and matrix mineralization in vivo. Mechanistically, we found that ICAM-1 enhances MSC proliferation but causes stem cell marker loss. Furthermore, overexpression of ICAM-1 stably activated the MAPK and NF-κB pathways but suppressed the PI3K/AKT pathway in MSCs. More importantly, specific inhibition of the ERK/MAPK and NF-κB pathways or activation of the PI3K/AKT pathway partially rescued osteogenic differentiation, while inhibition of the p38/MAPK and PI3K/AKT pathway caused more serious osteogenic suppression. In summary, our findings reveal a novel function of ICAM-1 in osteogenesis and suggest a new molecular target to improve bone regeneration and repair in inflammatory microenvironments.

  15. Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1.

    PubMed Central

    Baruch, D I; Gormely, J A; Ma, C; Howard, R J; Pasloske, B L

    1996-01-01

    Adherence of mature Plasmodium falciparum parasitized erythrocytes (PRBCs) to microvascular endothelium contributes directly to acute malaria pathology. We affinity purified molecules from detergent extracts of surface-radioiodinated PRBCs using several endothelial cell receptors known to support PRBC adherence, including CD36, thrombospondin (TSP), and intercellular adhesion molecule 1 (ICAM-1). All three host receptors affinity purified P. falciparum erythrocyte membrane protein 1 (PfEMP1), a very large malarial protein expressed on the surface of adherent PRBCs. Binding of PfEMP1 to particular host cell receptors correlated with the binding phenotype of the PRBCs from which PfEMP1 was extracted. Preadsorption of PRBC extracts with anti-PfEMP1 antibodies, CD36, or TSP markedly reduced PfEMP1 binding to CD36 or TSP. Mild trypsinization of intact PRBCs of P. falciparum strains shown to express antigenically different PfEMP1 released different (125)I-labeled tryptic fragments of PfEMP1 that bound specifically to CD36 and TSP. In clone C5 and strain MC, these activities resided on different tryptic fragments, but a single tryptic fragment from clone ItG-ICAM bound to both CD36 and TSP. Hence, the CD36- and TSP-binding domains are distinct entities located on a single PfEMP1 molecule. PfEMP1, the malarial variant antigen on infected erythrocytes, is therefore a receptor for CD36, TSP, and ICAM-1. A therapeutic approach to block or reverse adherence of PRBCs to host cell receptors can now be pursued with the identification of PfEMP1 as a malarial receptor for PRBC adherence to host proteins. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8622965

  16. Implication of intercellular adhesion molecule-1 (ICAM-1) and serum N(G)-hydroxy-L-arginine (L-NHA) in the pathogenesis of systemic sclerosis.

    PubMed

    Zamzam, Mona Lotfy; Yassin, Manal Mohamed; Sallam, Maha Mohamed

    2003-01-01

    In a trial to throw light on the implication of intercellular adhesion molecule-1 (ICAM-1) and N(G)-hydroxy-L-arginine (L-NHA) in the pathogenesis of systemic sclerosis or Scleroderma, (SSc), their serum levels were estimated in twenty SSc patients using ELISA and high performance liquid chromatography respectively. In situ "local" expression of ICAM-1 in lesional skin of these patients was also assessed using biotinstreptavidin amplified detection system. Patients were divided into 3 groups according to the cutaneous extension of sclerosis (Grades I; II & III). A significant (P < 0.001) difference was found between patients (n = 20) and controls (n = 10) regarding soluble ICAM-1 (s ICAM-1) and L-NHA levels. Among patients, a significant difference (P < 0.001, 0.05 respectively) in sICAM-1 & L-NHA serum levels was found between patients who had musculoskeletal manifestations and those who had not. A significant (P < 0.001) difference in L-NHA level was found between patients with grade I, II, III. Among patients, there was a negative correlation (r = -0.413) between serum sICAM-1 and the duration of the disease, and a positive correlation (r = +0.514) between sICAM-1 and L-NHA serum levels. 4 patients (23.6%) showed mild immunostaining, 8 patients (47%) showed moderate staining, and 5 patients (29.4%) showed intense staining, while control specimens showed negative immunostaining. In conclusion, ICAM-1 and serum L-NHA are probably implicated in the pathogenesis of SSc. Elevated sICAM-1 and L-NHA serum could be used as a quantitative marker of tissue sclerosis, allowing better follow up of patients.

  17. Serum Interleukin-18, Fetuin-A, Soluble Intercellular Adhesion Molecule-1, and Endothelin-1 in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome

    PubMed Central

    Przepiera-Będzak, Hanna; Fischer, Katarzyna; Brzosko, Marek

    2016-01-01

    To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC. PMID:27527149

  18. Tumour-derived interleukin 1alpha (IL-1alpha) up-regulates the release of soluble intercellular adhesion molecule-1 (sICAM-1) by endothelial cells.

    PubMed Central

    Fonsatti, E.; Altomonte, M.; Coral, S.; Cattarossi, I.; Nicotra, M. R.; Gasparollo, A.; Natali, P. G.; Maio, M.

    1997-01-01

    Levels of circulating soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in patients affected by solid malignancies; however, the cellular sources generating high levels of sICAM-1 remain to be characterized. Using conditioned media (CM) from seven ICAM-1-positive or -negative neoplastic cells, we demonstrate that tumour-derived interleukin 1alpha (IL-1alpha) significantly (P < 0.05) up-regulates the release of sICAM-1 by human umbilical vein endothelial cells. The intensity of the effect correlated with the amounts of IL-1alpha detectable in CM. Levels of ICAM-1 mRNA were also up-regulated by tumour-secreted IL-1alpha. The up-regulation of the shedding of sICAM-1 and of its expression at protein and mRNA level were completely reversed by the addition of anti-IL-1alpha neutralizing antibodies. Consistent with the in vitro data, tumour endothelia were strongly stained for ICAM-1 compared with autologous normal tissue endothelia. Taken altogether, our observations reveal an IL-1alpha-mediated tumour-endothelium relationship sustaining the shedding of sICAM-1 by endothelial cells. This is a general phenomenon in solid malignancies that correlates with the ability of neoplastic cells to secrete IL-1alpha rather than with their expression of ICAM-1 and/or histological origin. sICAM-1 has been previously shown to inhibit LFA-1/ICAM-1-mediated cell-cell interactions; therefore, the ability of neoplastic cells to secrete IL-1alpha is likely to represent a mechanism for their escape from immune interaction. Images Figure 5 Figure 6 PMID:9374368

  19. P2Y2 nucleotide receptor activation up-regulates vascular cell adhesion molecule-1 [corrected] expression and enhances lymphocyte adherence to a human submandibular gland cell line.

    PubMed

    Baker, Olga J; Camden, Jean M; Rome, Danny E; Seye, Cheikh I; Weisman, Gary A

    2008-01-01

    Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS.

  20. The P2Y2 nucleotide receptor mediates vascular cell adhesion molecule-1 expression through interaction with VEGF receptor-2 (KDR/Flk-1).

    PubMed

    Seye, Cheikh I; Yu, Ningpu; González, Fernando A; Erb, Laurie; Weisman, Gary A

    2004-08-20

    UTP stimulates the expression of pro-inflammatory vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells through activation of the P2Y(2) nucleotide receptor P2Y(2)R. Here, we demonstrated that activation of the P2Y(2)R induced rapid tyrosine phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2 in human coronary artery endothelial cells (HCAEC). RNA interference targeting VEGFR-2 or inhibition of VEGFR-2 tyrosine kinase activity abolishes P2Y(2)R-mediated VCAM-1 expression. Furthermore, VEGFR-2 and the P2Y(2)R co-localize upon UTP stimulation. Deletion or mutation of two Src homology-3-binding sites in the C-terminal tail of the P2Y(2)R or inhibition of Src kinase activity abolished the P2Y(2)R-mediated transactivation of VEGFR-2 and subsequently inhibited UTP-induced VCAM-1 expression. Moreover, activation of VEGFR-2 by UTP leads to the phosphorylation of Vav2, a guanine nucleotide exchange factor for Rho family GTPases. Using a binding assay to measure the activity of the small GTPases Rho, we found that stimulation of HCAEC by UTP increased the activity of RhoA and Rac1 (but not Cdc42). Significantly, a dominant negative form of RhoA inhibited P2Y(2)R-mediated VCAM-1 expression, whereas expression of dominant negative forms of Cdc42 and Rac1 had no effect. These data indicate a novel mechanism whereby a nucleotide receptor transactivates a receptor tyrosine kinase to generate an inflammatory response associated with atherosclerosis.

  1. Serum Interleukin-18, Fetuin-A, Soluble Intercellular Adhesion Molecule-1, and Endothelin-1 in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome.

    PubMed

    Przepiera-Będzak, Hanna; Fischer, Katarzyna; Brzosko, Marek

    2016-01-01

    To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC. PMID:27527149

  2. Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium falciparum-Infected Erythrocytes to Endothelial Cells

    PubMed Central

    Avril, Marion; Bernabeu, Maria; Benjamin, Maxwell; Brazier, Andrew Jay

    2016-01-01

    ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum-infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. PMID:27406562

  3. The Serum Changes of Neuron-Specific Enolase and Intercellular Adhesion Molecule-1 in Patients With Diffuse Axonal Injury Following Progesterone Administration: A Randomized Clinical Trial

    PubMed Central

    Shahrokhi, Nader; Soltani, Zahra; Khaksari, Mohammad; Karamouzian, Saeid; Mofid, Behshad; Asadikaram, Gholamreza

    2016-01-01

    Background Improvement of neurologic outcome in progesterone-administered patients with diffuse axonal injury (DAI) has been found in a recent study. Also, there has been interest in the importance of serum parameters as predictors of outcome in traumatic brain injury. Objectives The aim of this study was to examine the effect of progesterone administration on serum levels of neuron-specific enolase (NSE), and intercellular adhesion molecule-1 (ICAM-1) in clinical DAI. Patients and Methods In this study, the serum levels of ICAM-1 and NSE of 32 male DAI patients (18 - 60 years of age, a Glasgow coma scale of 12 or less, and admitted within 4 hours after injury) who were randomized for a controlled phase II trial of progesterone were analyzed. The analysis was performed between the control and progesterone groups at admission time, and 24 hours and six days after DAI, respectively. Results A reduction in the serum level of ICAM-1 was noticed in the progesterone group 24 hours after the injury (P < 0.05). There was no significant difference in the serum level of NSE between the study groups during evaluation. At 24 hours after the injury, the level of ICAM-1 in the control group was higher than that at admission time (P < 0.05). The lowest level of NSE in the two groups was seen six days after DAI (P < 0.01). Conclusions In summary, progesterone administration reduced serum ICAM-1, and whereby may attenuate blood brain barrier disruption, the latter needs further investigation for confirmation. PMID:27800469

  4. Characterization of the oligodeoxynucleotide-mediated inhibition of interferon-gamma-induced major histocompatibility complex class I and intercellular adhesion molecule-1.

    PubMed

    Ramanathan, M; Lantz, M; MacGregor, R D; Garovoy, M R; Hunt, C A

    1994-10-01

    The major histocompatibility complex (MHC) Class I and II genes and intercellular adhesion molecule-1 (ICAM-1) are regulated by interferon-gamma in a variety of cell types. We have previously shown that the oligodeoxynucleotide 5'-GGG GTT GGT TGT GTT GGG TGT TGT GT-RNH2 (oligo I) inhibits the interferon-gamma-mediated enhancement of MHC Class I and ICAM-1 proteins in the K562 cell line. We have now investigated the mechanism of action of oligo I and report that it acts by inhibiting the binding of interferon-gamma to cells. We also show that the dose-response curves, the selectivity profile, and the kinetics of oligo I are consistent with this novel mechanism of action. The dose-response curves for oligo I, obtained using antibodies against the MHC Class I heavy chain, beta 2-microglobulin, or ICAM-1, are almost superimposable at each observation time. MHC Class I induction by 6400 units/ml interferon-alpha or interferon-beta or ICAM-1 enhancement by 800 units/ml tumor necrosis factor-alpha is not inhibited by oligo I. However, the synergistic induction of MHC Class I by mixtures of tumor necrosis factor-alpha and interferon-gamma is inhibited. Oligo I belongs to a class of active oligodeoxynucleotides that inhibits interferon-gamma-induced MHC Class I and ICAM-1 in K562 cells. The activity and potency is sequence-dependent, but remarkably different sequences can have comparable effects. The activity of oligo I in the HeLa S3 cell line inhibits the interferon-gamma-mediated enhancement of both ICAM-1 and MHC Class II DR and the interferon-gamma-mediated reduction in transferrin receptor expression. Thus, oligo I appears to specifically inhibit interferon-gamma-induced changes in protein expression, which is consistent with oligo I acting at an early step(s) in the induction process. Taken together, our results show that oligo I exerts its effects by inhibiting the association of interferon-gamma with the cell surface, which is a novel mechanism of action for

  5. Ultraviolet radiation can either suppress or induce expression of intercellular adhesion molecule 1 (ICAM-1) on the surface of cultured human keratinocytes

    SciTech Connect

    Norris, D.A.; Lyons, M.B.; Middleton, M.H.; Yohn, J.J.; Kashihara-Sawami, M. )

    1990-08-01

    Interactions of the ligand/receptor pair LFA-1(CD11a/CD18) and ICAM-1(CD54) initiate and control the cell-cell interactions of leukocytes and interactions of leukocytes with parenchymal cells in all phases of the immune response. Induction of the intercellular adhesion molecule 1 (ICAM-1) on the surface of epidermal keratinocytes has been proposed as an important regulator of contact-dependent aspects of cutaneous inflammation. Ultraviolet radiation (UVR) also modifies cutaneous inflammation, producing both up- and down-regulation of contact hypersensitivity. We have found that UVR has a biphasic effect on the induction of keratinocyte CD54. Using immunofluorescence and FACS techniques to quantitate cell-surface CD54 staining, we have shown that UVR significantly (p less than 0.01) inhibits keratinocyte CD54 induction by gamma interferon 24 h after irradiation. However, at 48, 72, and 96 h after UVR, CD54 expression is significantly induced to levels even greater than are induced by gamma interferon (20 U/ml). In addition, at 48, 72, or 96 h following UVR (30-100 mJ/cm2), the gamma-interferon-induced CD54 expression on human keratinocytes is also strongly (p less than 0.05 to p less than 0.001) enhanced. In this cell-culture system, gamma interferon and TNF-alpha are both strong CD54 inducers and are synergistic, but GM-CSF, TFG-beta, and IL-1 have no direct CD54-inducing effects. Thus the effects of UVR on CD54 induction are biphasic, producing inhibition at 24 h and induction at 48, 72, and 96 h. This effect on CD54 may contribute to the biphasic effects of UVR on delayed hypersensitivity in vivo. The early inhibition of ICAM-1 by UVR may also contribute to the therapeutic effects of UVR. We also speculate that the late induction of ICAM-1 by UVR might be an important step in the induction of photosensitive diseases such as lupus erythematosus.

  6. Expression profile of vascular cell adhesion molecule-1 (CD106) in inflammatory foci using rhenium-188 labelled monoclonal antibody in mice.

    PubMed

    Kairemo, K J; Strömberg, S; Nikula, T K; Karonen, S L

    1998-06-01

    Rhenium (Re)-188 is a generator (W-188/Re-188) produced high energy beta-emitter suitable for radionuclide therapy (T1/2 is 16.9 hrs and Emax 2.1 MeV (range 11 mm)). We have labelled monoclonal antibody (MAb) raised against vascular cell adhesion molecule-1 (VCAM-1) with Re-188 using glucoheptonate chelation technique and SnCl2 as reducing agent. The labelling efficiency, free perrhenate and reduced Re were controlled with thin layer chromatography and the purification of Re-188-MoAbs was performed using gel filtration. Our results indicate that Re-188-labelled antibodies remain in vitro stable and the labelling purity is > 90%. We also have applied these Re-188-MoAbs for detection of inflammatory disease in a mouse. The effective half-lives of organs of interest after an injection of Re-188-anti-VCAM1 were as follows: blood 5.2 hr, kidney 4.7 hr, and liver 9.6 hr. Re-188-anti-VCAM-1 was found to accumulate mainly in kidney and liver. One hour after the injection, the kidney contained in average as high as 12.5% and the liver 2.8 ID/g tissue. After 6 hr, the kidney contained 5.5% ID/g and the liver 2.6% ID/g. At 24 hr, the kidney uptake was 0.5% ID/g and the liver uptake 0.8% ID/g, respectively. The inflamed foci, subcutaneous lesions in the footpad skin, were visualized using gamma camera. From the distribution data the uptakes in the inflamed foci as follows: at 1 hr 2.18 (inflammation) and 1.72% ID/g (control), at 6 hr 1.42 (inflammation) and 0.85% ID/g (control), and at 24 hr 0.17 (inflammation) and 0.084% ID/g (control), respectively. Anti-VCAM-1 MAb showed better targeting as compared to control MoAbs in inflammation (caused by E.coli lipoplysaccaride). In conclusion, Re-188 is suitable for MAb labelling, and MAb against VCAM-1 may be used for detection of local inflammatory disease. PMID:9762472

  7. Residues within a lipid-associated segment of the PECAM-1 cytoplasmic domain are susceptible to inducible, sequential phosphorylation.

    PubMed

    Paddock, Cathy; Lytle, Betsy L; Peterson, Francis C; Holyst, Trudy; Newman, Peter J; Volkman, Brian F; Newman, Debra K

    2011-06-01

    Immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors inhibit cellular responsiveness to immunoreceptor tyrosine-based activation motif (ITAM)-linked receptors. Although tyrosine phosphorylation is central to the initiation of both inhibitory ITIM and stimulatory ITAM signaling, the events that regulate receptor phosphorylation are incompletely understood. Previous studies have shown that ITAM tyrosines engage in structure-inducing interactions with the plasma membrane that must be relieved for phosphorylation to occur. Whether ITIM phosphorylation is similarly regulated and the mechanisms responsible for release from plasma membrane interactions to enable phosphorylation, however, have not been defined. PECAM-1 is a dual ITIM-containing receptor that inhibits ITAM-dependent responses in hematopoietic cells. We found that the PECAM-1 cytoplasmic domain is unstructured in an aqueous environment but adopts an α-helical conformation within a localized region on interaction with lipid vesicles that mimic the plasma membrane. The lipid-interacting segment contains the C-terminal ITIM tyrosine and a serine residue that undergo activation-dependent phosphorylation. The N-terminal ITIM is excluded from the lipid-interacting segment, and its phosphorylation is secondary to phosphorylation of the membrane-interacting C-terminal ITIM. On the basis of these findings, we propose a novel model for regulation of inhibitory signaling by ITIM-containing receptors that relies on reversible plasma membrane interactions and sequential ITIM phosphorylation. PMID:21464369

  8. Platelet adhesion signalling and the regulation of thrombus formation.

    PubMed

    Gibbins, Jonathan M

    2004-07-15

    Platelets perform a central role in haemostasis and thrombosis. They adhere to subendothelial collagens exposed at sites of blood vessel injury via the glycoprotein (GP) Ib-V-IX receptor complex, GPVI and integrin alpha(2)beta(1). These receptors perform distinct functions in the regulation of cell signalling involving non-receptor tyrosine kinases (e.g. Src, Fyn, Lyn, Syk and Btk), adaptor proteins, phospholipase C and lipid kinases such as phosphoinositide 3-kinase. They are also coupled to an increase in cytosolic calcium levels and protein kinase C activation, leading to the secretion of paracrine/autocrine platelet factors and an increase in integrin receptor affinities. Through the binding of plasma fibrinogen and von Willebrand Factor to integrin alpha(IIb)beta(3), a platelet thrombus is formed. Although increasing evidence indicates that each of the adhesion receptors GPIb-V-IX and GPVI and integrins alpha(2)beta(1) and alpha(IIb)beta(3) contribute to the signalling that regulates this process, the individual roles of each are only beginning to be dissected. By contrast, adhesion receptor signalling through platelet endothelial cell adhesion molecule 1 (PECAM-1) is implicated in the inhibition of platelet function and thrombus formation in the healthy circulation. Recent studies indicate that understanding of platelet adhesion signalling mechanisms might enable the development of new strategies to treat and prevent thrombosis. PMID:15252124

  9. Lipid rafts facilitate the interaction of PECAM-1 with the glycoprotein VI-FcR gamma-chain complex in human platelets.

    PubMed

    Lee, Fiona A; van Lier, Marjolijn; Relou, Ingrid A M; Foley, Loraine; Akkerman, Jan-Willem N; Heijnen, Harry F G; Farndale, Richard W

    2006-12-22

    Glycoprotein (GP) VI, the main signaling receptor for collagen on platelets, is expressed in complex with the FcR gamma-chain. The latter contains an immunoreceptor tyrosine-based activation motif, which becomes phosphorylated, initiating a signaling cascade leading to the rapid activation and aggregation of platelets. Previous studies have shown that signaling by immunoreceptor tyrosine-based activation motif-containing receptors is counteracted by signals from receptors with immunoreceptor tyrosine-based inhibitory motifs. Here we show, by immunoprecipitation, that the GPVI-FcR gamma-chain complex associates with the immunoreceptor tyrosine-based inhibitory motif-containing receptor, PECAM-1. In platelets stimulated with collagen-related peptide (CRP-XL), tyrosine phosphorylation of PECAM-1 precedes that of the FcR gamma-chain, implying direct regulation of the former. The GPVI-FcR gamma-chain complex and PECAM-1 were present in both lipid raft and soluble fractions in human platelets; this distribution was unaltered by activation with CRP-XL. Their association occurred in lipid rafts and was lost after lipid raft depletion using methyl-beta-cyclodextrin. We propose that lipid raft clustering facilitates the interaction of PECAM-1 with the GPVI-FcR gamma-chain complex, leading to the down-regulation of the latter. PMID:17068334

  10. Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils.

    PubMed Central

    Parkos, C. A.; Colgan, S. P.; Diamond, M. S.; Nusrat, A.; Liang, T. W.; Springer, T. A.; Madara, J. L.

    1996-01-01

    BACKGROUND: Epithelial dysfunction and patient symptoms in inflammatory intestinal diseases such as ulcerative colitis and Crohn's disease correlate with migration of neutrophils (PMN) across the intestinal epithelium. In vitro modeling of PMN transepithelial migration has revealed distinct differences from transendothelial migration. By using polarized monolayers of human intestinal epithelia (T84), PMN transepithelial migration has been shown to be dependent on the leukocyte integrin CD11b/CD18 (Mac-1), but not on CD11a/CD18 (LFA-1). Since intercellular adhesion molecule-I (ICAM-1) is an important endothelial counterreceptor for these integrins, its expression in intestinal epithelia and role in PMN-intestinal epithelial interactions was investigated. MATERIALS AND METHODS: A panel of antibodies against different domains of ICAM-1, polarized monolayers of human intestinal epithelia (T84), and natural human colonic epithelia were used to examine the polarity of epithelial ICAM-1 surface expression and the functional role of ICAM-1 in neutrophil-intestinal epithelial adhesive interactions. RESULTS: While no surface expression of ICAM-1 was detected on unstimulated T84 cells, interferon-gamma (IFN gamma) elicited a marked expression of ICAM-1 that selectively polarized to the apical epithelial membrane. Similarly, apically restricted surface expression of ICAM-1 was detected in natural human colonic epithelium only in association with active inflammation. With or without IFN gamma pre-exposure, physiologically directed (basolateral-to-apical) transepithelial migration of PMN was unaffected by blocking monoclonal antibodies (mAbs) to ICAM-1. In contrast, PMN migration across IFN gamma-stimulated monolayers in the reverse (apical-to-basolateral) direction was inhibited by anti-ICAM-1 antibodies. Adhesion studies revealed that T84 cells adhered selectively to purified CD11b/CD18 and such adherence, with or without IFN gamma pre-exposure, was unaffected by ICAM-1 m

  11. Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease.

    PubMed

    Nakamura, Tatsufumi; Satoh, Katsuya; Fukuda, Taku; Kinoshita, Ikuo; Nishiura, Yoshihiro; Nagasato, Kunihiko; Yamauchi, Atsushi; Kataoka, Yasufumi; Nakamura, Tadahiro; Sasaki, Hitoshi; Kumagai, Kenji; Niwa, Masami; Noguchi, Mitsuru; Nakamura, Hideki; Nishida, Noriyuki; Kawakami, Atsushi

    2014-06-01

    The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

  12. Nuclear factor-kappa B directs carcinoembryonic antigen-related cellular adhesion molecule 1 receptor expression in Neisseria gonorrhoeae-infected epithelial cells.

    PubMed

    Muenzner, Petra; Billker, Oliver; Meyer, Thomas F; Naumann, Michael

    2002-03-01

    The human-specific pathogen Neisseria gonorrhoeae expresses opacity-associated (Opa) protein adhesins that bind to various members of the carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) family. In this study, we have analyzed the mechanism underlying N. gonorrhoeae-induced CEACAM up-regulation in epithelial cells. Epithelial cells represent the first barrier for the microbial pathogen. We therefore characterized CEACAM expression in primary human ovarian surface epithelial (HOSE) cells and found that CEACAM1-3 (L, S) and CEACAM1-4 (L, S) splice variants mediate an increased Opa(52)-dependent gonoccocal binding to HOSE cells. Up-regulation of these CEACAM molecules in HOSE cells is a direct process that takes place within 2 h postinfection and depends on close contact between microbial pathogen and HOSE cells. N. gonorrhoeae-triggered CEACAM1 up-regulation involves activation of the transcription factor nuclear factor kappaB (NF-kappaB), which translocates as a p50/p65 heterodimer into the nucleus, and an NF-kappaB-specific inhibitory peptide inhibited CEACAM1-receptor up-regulation in N. gonorrhoeae-infected HOSE cells. Bacterial lipopolysaccharides did not induce NF-kappaB and CEACAM up-regulation, which corresponds to our findings that HOSE cells do not express toll-like receptor 4. The ability of N. gonorrhoeae to up-regulate its epithelial receptor CEACAM1 through NF-kappaB suggests an important mechanism allowing efficient bacterial colonization during the initial infection process. PMID:11751883

  13. 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

    PubMed Central

    Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

    2016-01-01

    Objective: 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 (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. Results: 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. 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 might thus improve cardiovascular outcomes. PMID:27610083

  14. 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

    PubMed Central

    Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

    2016-01-01

    Objective: 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 (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. Results: 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. 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 might thus improve cardiovascular outcomes.

  15. α4-Integrin Antibody Treatment Blocks Monocyte/Macrophage Traffic to, Vascular Cell Adhesion Molecule-1 Expression in, and Pathology of the Dorsal Root Ganglia in an SIV Macaque Model of HIV-Peripheral Neuropathy.

    PubMed

    Lakritz, Jessica R; Thibault, Derek M; Robinson, Jake A; Campbell, Jennifer H; Miller, Andrew D; Williams, Kenneth C; Burdo, Tricia H

    2016-07-01

    Traffic of activated monocytes into the dorsal root ganglia (DRG) is critical for pathology in HIV peripheral neuropathy. We have shown that accumulation of recently recruited (bromodeoxyuridine(+) MAC387(+)) monocytes is associated with severe DRG pathology and loss of intraepidermal nerve fibers in SIV-infected macaques. Herein, we blocked leukocyte traffic by treating animals with natalizumab, which binds to α4-integrins. SIV-infected CD8-depleted macaques treated with natalizumab either early (the day of infection) or late (28 days after infection) were compared with untreated SIV-infected animals sacrificed at similar times. Histopathology showed diminished DRG pathology with natalizumab treatment, including decreased inflammation, neuronophagia, and Nageotte nodules. Natalizumab treatment resulted in a decrease in the number of bromodeoxyuridine(+) (early), MAC387(+) (late), CD68(+) (early and late), and SIVp28(+) (late) macrophages in DRG tissues. The number of CD3(+) T lymphocytes in DRGs was not affected by natalizumab treatment. Vascular cell adhesion molecule 1, an adhesion molecule that mediates leukocyte traffic, was diminished in DRGs of all natalizumab-treated animals. These data show that blocking monocyte, but not T lymphocyte, traffic to the DRG results in decreased inflammation and pathology, supporting a role for monocyte traffic and activation in HIV peripheral neuropathy. PMID:27157989

  16. A preliminary study of pamidronic acid downregulation of angiogenic factors IGF-1/PECAM-1 expression in circulating level in bone metastatic breast cancer patients

    PubMed Central

    Wang, Zeng; Lei, Lei; Cai, Xin-jun; Chen, Ling Ya; Yuan, Meiqin; Yang, Guonong; Huang, Ping; Wang, Xiaojia

    2016-01-01

    Objective To evaluate the expressions of circulating angiogenic factors affected by pamidronic acid (PA) intravenous infusion in bone metastatic breast cancer patients and the impact on their prognosis. Methods Peripheral blood of ten bone metastatic breast cancer patients was collected for serum insulin-like growth factor-1 (IGF-1) and platelet endothelial cell adhesion molecule-1 expression detection just before and 2 days after PA infusion. Results Both IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations decreased after PA treatment for 48 hours (P<0.05). Modification was defined as >20% decrease recorded 2 days after PA administration. The decrease of IGF-1 was more significant in breast cancer patients who had received previous hormonotherapy. Moreover, the progression-free survival of first-line chemotherapy treatment of IGF-1 modified patients was longer than that of IGF-1 unmodified patients (P=0.009). Conclusion PA treatment could suppress circulating serum IGF-1 and platelet endothelial cell adhesion molecule-1 concentrations; moreover, the prognosis of patients in IGF-1 unmodified group was relatively poor. PMID:27307756

  17. Beneficial Effects of Coenzyme Q10 Supplementation on Lipid Profile and Intereukin-6 and Intercellular Adhesion Molecule-1 Reduction, Preliminary Results of a Double-blind Trial in Acute Myocardial Infarction

    PubMed Central

    Mohseni, Mona; Vafa, Mohammadreza; Zarrati, Mitra; Shidfar, Farzad; Hajimiresmail, Seyed Javad; Rahimi Forushani, Abbas

    2015-01-01

    Background: The present investigation was aimed to improve the inflammatory factors and lipoproteins concentration in patients with myocardial infarction (MI) by supplementation with coenzyme Q10 (CoQ10). Methods: In a double-blind, placebo-controlled study, we measured serum concentrations of one soluble cell adhesion molecules (intercellular adhesion molecule-1 [ICAM-1]), serum concentration of intereukin-6 (IL-6) and lipid profiles (high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], total cholesterol and triglyceride [TG]) in CoQ10 supplementation group (n = 26) compared with placebo group (n = 26) in hyperlipidemic patients with MI. Fifty-two patients were randomized to receive 200 mg/day of CoQ10 or placebo for 12 weeks. Results: There were no significant differences for serum LDL-C, total cholesterol, and TG between two mentioned groups after the intervention. A significant enhancement in serum HDL-C level was observed between groups after the intervention (55.46 ± 6.87 and 44.07 ± 6.99 mg/dl in CoQ10 and placebo groups, respectively P < 0.001). Concentrations of ICAM-1 (415.03 ± 96.89 and 453.38 ± 0.7 ng/dl CoQ10 and placebo groups, respectively, P = 0.001) and IL-6 (11 ± 9.57 and 12.55 ± 8.76 pg/ml CoQ10 and placebo groups, respectively P = 0.001) in serum were significantly decreased in CoQ10 group. Conclusions: Supplementation with CoQ10 in hyperlipidemic patients with MI that have statin therapy has beneficial effects on their aspects of health. PMID:26330989

  18. Small GTPase Rho signaling is involved in {beta}1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor {kappa}B ligand on osteoblasts and osteoclast maturation

    SciTech Connect

    Hirai, Fumihiko; Nakayamada, Shingo; Okada, Yosuke; Saito, Kazuyoshi; Kurose, Hitoshi; Mogami, Akira; Tanaka, Yoshiya . E-mail: tanaka@med.uoeh-u.ac.jp

    2007-04-27

    We assessed the characteristics of human osteoblasts, focusing on small GTPase Rho signaling. {beta}1 Integrin were highly expressed on osteoblasts. Engagement of {beta}1 integrins by type I collagen augmented expression of intercellular adhesion molecule 1 (ICAM-1) and receptor activator of nuclear factor {kappa}B ligand (RANKL) on osteoblasts. Rho was activated by {beta}1 stimulation in osteoblasts. {beta}1 Integrin-induced up-regulation of ICAM-1 and RANKL was inhibited by transfection with adenoviruses encoding C3 transferase or pretreated with Y-27632, specific Rho and Rho-kinase inhibitors. Engagement of {beta}1 integrin on osteoblasts induced formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNC) in a coculture system of osteoblasts and peripheral monocytes, but this action was completely abrogated by transfection of C3 transferase. Our results indicate the direct involvement of Rho-mediated signaling in {beta}1 integrin-induced up-regulation of ICAM-1 and RANKL and RANKL-dependent osteoclast maturation. Thus, Rho-mediated signaling in osteoblasts seems to introduce major biases to bone resorption.

  19. Mechanistic Control of Carcinoembryonic Antigen-related Cell Adhesion Molecule-1 (CEACAM1) Splice Isoforms by the Heterogeneous Nuclear Ribonuclear Proteins hnRNP L, hnRNP A1, and hnRNP M*

    PubMed Central

    Dery, Kenneth J.; Gaur, Shikha; Gencheva, Marieta; Yen, Yun; Shively, John E.; Gaur, Rajesh K.

    2011-01-01

    Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is expressed in a variety of cell types and is implicated in carcinogenesis. Alternative splicing of CEACAM1 pre-mRNA generates two cytoplasmic domain splice variants characterized by the inclusion (L-isoform) or exclusion (S-isoform) of exon 7. Here we show that the alternative splicing of CEACAM1 pre-mRNA is regulated by novel cis elements residing in exon 7. We report the presence of three exon regulatory elements that lead to the inclusion or exclusion of exon 7 CEACAM1 mRNA in ZR75 breast cancer cells. Heterologous splicing reporter assays demonstrated that the maintenance of authentic alternative splicing mechanisms were independent of the CEACAM1 intron sequence context. We show that forced expression of these exon regulatory elements could alter CEACAM1 splicing in HEK-293 cells. Using RNA affinity chromatography, three members of the heterogeneous nuclear ribonucleoprotein family (hnRNP L, hnRNP A1, and hnRNP M) were identified. RNA immunoprecipitation of hnRNP L and hnRNP A1 revealed a binding motif located central and 3′ to exon 7, respectively. Depletion of hnRNP A1 or L by RNAi in HEK-293 cells promoted exon 7 inclusion, whereas overexpression led to exclusion of the variable exon. By contrast, overexpression of hnRNP M showed exon 7 inclusion and production of CEACAM1-L mRNA. Finally, stress-induced cytoplasmic accumulation of hnRNP A1 in MDA-MB-468 cells dynamically alters the CEACAM1-S:CEACAM1:L ratio in favor of the l-isoform. Thus, we have elucidated the molecular factors that control the mechanism of splice-site recognition in the alternative splicing regulation of CEACAM1. PMID:21398516

  20. Zinc oxide nanoparticles-induced intercellular adhesion molecule 1 expression requires Rac1/Cdc42, mixed lineage kinase 3, and c-Jun N-terminal kinase activation in endothelial cells.

    PubMed

    Li, Ching-Hao; Liao, Po-Lin; Shyu, Ming-Kwang; Liu, Chen-Wei; Kao, Chen-Chieh; Huang, Shih-Hsuan; Cheng, Yu-Wen; Kang, Jaw-Jou

    2012-03-01

    The explosive development of nanotechnology has caused an increase in unintended biohazards in humans and in the ecosystem. Similar to particulate matter, nanoparticles (NPs) are strongly correlated with the increase in incidences of cardiovascular diseases, yet the mechanisms behind this correlation remain unclear. Within the testing concentrations of 0.1-10 μg/ml, which did not cause a marked drop in cell viability, zinc oxide NPs (ZnO-NPs) induced intercellular adhesion molecule-1 (ICAM-1) messenger RNA, and protein expression in both concentration- and time-dependent manner in treated human umbilical vein endothelial cells (HUVECs). ZnO-NPs treatment cause the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1)/cell division control protein 42 homolog (Cdc42) and protein accumulation of mixed lineage kinase 3 (MLK3), followed by c-Jun N-terminal kinase (JNK) and transcription factor c-Jun activation. Induction of ICAM-1 and phosphorylation of JNK and c-Jun could be inhibited by either JNK inhibitor SP600125 or Rac guanosine triphosphatase inhibitor NSC23766 pretreatment. In addition, pretreatment with NSC23766 significantly reduced MLK3 accumulation, suggesting the involvement of Rac1/Cdc42-MLK3-JNK-c-Jun signaling in the regulation of ZnO-NPs-induced ICAM-1 expression, whereas these signaling factors were not activated in zinc oxide microparticles (ZnO-MPs)-treated HUVECs. The increase of ICAM-1 expression on ZnO-NPs-treated HUVECs enables leukocytes to adhere and has been identified as an indicator of vascular inflammation. Our data are essential for safety evaluation of the clinical usage of ZnO-NPs in daily supplements, cosmetics, and biomedicines.

  1. Aldosterone stimulates nuclear factor-kappa B activity and transcription of intercellular adhesion molecule-1 and connective tissue growth factor in rat mesangial cells via serum- and glucocorticoid-inducible protein kinase-1.

    PubMed

    Terada, Yoshio; Ueda, Satoko; Hamada, Kazu; Shimamura, Yoshiko; Ogata, Koji; Inoue, Kosuke; Taniguchi, Yoshinori; Kagawa, Toru; Horino, Taro; Takao, Toshihiro

    2012-02-01

    Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. To determine the signaling pathway of aldosterone in relation to fibrosis and inflammation in mesangial cells, we investigated the effects of aldosterone on expression and activation of serum- and glucocorticoid-inducible protein kinase-1 (SGK1), the activation of nuclear factor-kappa B (NF-κB activation, and the expressions of intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF). Aldosterone stimulated SGK1 expression, phosphorylation (Ser-256), and kinase activity. The increments of phosphorylation and expression of SGK1 induced by aldosterone were inhibited by mineralocorticoid receptor (MR) inhibitor (eplerenone). Aldosterone stimulated NF-κB activity measured by NF-κB responsive elements, luciferase assay, and the levels of inhibitor of kappa B (IκB) phosphorylation. This aldosterone-induced activation of NF-κB was inhibited by the transfection of dominant-negative SGK1. Furthermore, aldosterone augmented the promoter activities and protein expressions of ICAM-1 and CTGF. The effects of aldosterone on ICAM-1 and CTGF promoter activities and protein expressions were inhibited by the transfection of dominant-negative SGK1 and dominant-negative IκBα. We also found that the MR antagonist significantly ameliorated the glomerular injury and enhancements in SGK1, ICAM-1, and CTGF expressions induced by 1% sodium chloride and aldosterone in vivo. In conclusion, our findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via activation of SGK1 and NF-κB, which may be involved in the progression of aldosterone-induced mesangial fibrosis and inflammation. MR antagonists may serve as useful therapeutic targets for the treatment of glomerular inflammatory disease.

  2. Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum, the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections

    PubMed Central

    Lee, Sung-Hoon; Kim, Kack-Kyun; Choi, Bong-Kyu

    2005-01-01

    Treponema maltophilum and Treponema lecithinolyticum belong to the group IV oral spirochetes and are associated with endodontic infections, as well as periodontitis. Recently, the genes encoding the major surface proteins (Msps) of these bacteria (MspA and MspTL, respectively) were cloned and sequenced. The amino acid sequences of these proteins showed significant similarity. In this study we analyzed the functional role of these homologous proteins in human monocytic THP-1 cells and primary cultured periodontal ligament (PDL) cells using recombinant proteins. The complete genes encoding MspA and MspTL without the signal sequence were cloned into Escherichia coli by using the expression vector pQE-30. Fusion proteins tagged with N-terminal hexahistidine (recombinant MspA [rMspA] and rMspTL) were obtained, and any possible contamination of the recombinant proteins with E. coli endotoxin was removed by using polymyxin B-agarose. Flow cytometry showed that rMspA and rMspTL upregulated the expression of intercellular adhesion molecule 1 (ICAM-1) in both THP-1 and PDL cells. Expression of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, was also induced significantly in both cell types by the Msps, as determined by reverse transcription-PCR and an enzyme-linked immunosorbent assay, whereas IL-1β synthesis could be detected only in the THP-1 cells. The upregulation of ICAM-1, IL-6, and IL-8 was completely inhibited by pretreating the cells with an NF-κB activation inhibitor, l-1-tosylamido-2-phenylethyl chloromethyl ketone. This suggests involvement of NF-κB activation. The increased ICAM-1 and IL-8 expression in the THP-1 cells obtained with rMsps was not inhibited in the presence of the IL-1 receptor antagonist (IL-1ra), a natural inhibitor of IL-1. Our results show that the Msps of the group IV oral spirochetes may play an important role in amplifying the local immune response by continuous inflammatory cell recruitment and retention at an

  3. Adhesion

    MedlinePlus

    ... as the shoulder Eyes Inside the abdomen or pelvis Adhesions can become larger or tighter over time. ... Other causes of adhesions in the abdomen or pelvis include: Appendicitis , most often when the appendix breaks ...

  4. R643G polymorphism in PECAM-1 influences transendothelial migration of monocytes and is associated with progression of CHD and CHD events.

    PubMed

    Elrayess, Mohamed A; Webb, Karen E; Bellingan, Geoff J; Whittall, Ros A; Kabir, Jahangir; Hawe, Emma; Syvänne, Mikko; Taskinen, Marja-Riitta; Frick, M Heikki; Nieminen, Markku S; Kesäniemi, Y Antero; Pasternack, Amos; Miller, George J; Humphries, Steve E

    2004-11-01

    The 643R allele of R643G polymorphism (also known as R670G in the premature protein) in PECAM-1 has been associated with risk of myocardial infarction (MI), while the 643G allele has been associated with risk of coronary artery stenosis (CAS). The aim of this study was to investigate this apparently conflicting association. The association of R643G with risk of MI was determined in the second Northwick Park Heart study (2037 men with 138 CHD events; mean age: 56 years). Smokers homozygous for the 643R allele showed increased risk of MI with a hazard ratio of 2.47 (95% CI: 1.23-4.97; P=0.01) compared to smokers homozygous for the 643G allele. Progression of disease was determined in the Lopid Coronary Angiography Trial (279 men; mean age: 58.9 years). The 643G homozygotes showed greater focal (-0.08 +/- 0.02 mm) and diffuse (-0.01 +/- 0.01 mm) progression of CAS compared to 643R homozygotes (-0.02 +/- 0.02 mm and 0.001 +/- 0.01 mm, respectively; P=0.04). While there was no genotype effect on platelet aggregation, PECAM-1 tyrosine phosphorylation in HUVECs of GG genotype was 2.4-fold greater (P <0.01) than cells of RR genotype, and the level of transendothelial migration of monocytes of GG genotype was greater than that of monocytes of RR genotype following stimulation with either IL-1beta (12% higher, P <0.01) or TNF-alpha (10% higher, P=0.05). These data confirm the association of the R643G polymorphism with MI and CAS and suggest that greater influx of monocytes in individuals homozygous for the 643G may explain the association with CAS. PMID:15488875

  5. Role of lateral cell-cell border location and extracellular/transmembrane domains in PECAM/CD31 mechanosensation.

    PubMed

    Kaufman, David A; Albelda, Steven M; Sun, Jing; Davies, Peter F

    2004-08-01

    Phosphorylation of tyrosine residues on platelet-endothelial cell adhesion molecule-1 (PECAM-1), followed by signal transduction events, has been described in endothelial cells following exposure to hyperosmotic and fluid shear stress. However, it is unclear whether PECAM-1 functions as a primary mechanosensor in this process. Utilizing a PECAM-1-null EC-like cell line, we examined the importance of cellular localization and the extracellular and transmembrane domains in PECAM-1 phosphorylation responses to mechanical stress. Tyrosine phosphorylation of PECAM-1 was stimulated in response to mechanical stress in null cells transfected either with full length PECAM-1 or with PECAM-1 mutants that do not localize to the lateral cell-cell adhesion site and that do not support homophilic binding between PECAM-1 molecules. Furthermore, null cells transfected with a construct that contains the intact cytoplasmic domain of PECAM-1 fused to the extracellular and transmembrane domains of the interleukin-2 receptor also underwent mechanical stress-induced PECAM-1 tyrosine phosphorylation. These findings suggest that mechanosensitive PECAM-1 may lie downstream of a primary mechanosensor that activates a tyrosine kinase. PMID:15249199

  6. Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of PECAM-1

    PubMed Central

    1995-01-01

    During the inflammatory response, the adhesion molecule PECAM plays a crucial role in transendothelial migration, the passage of leukocytes across endothelium. We report here an additional role for PECAM in the subsequent migration of monocytes through the subendothelial extracellular matrix. PECAM has six immunoglobulin (Ig) superfamily domains. Monoclonal antibodies whose epitopes map to domains 1 and/or 2 selectively block monocyte migration through the endothelial junction, whereas those that map to domain 6 block only the migration through the extracellular matrix, trapping the monocyte between the endothelium and its basal lamina. Therefore, transendothelial migration (diapedesis) and passage through extracellular matrix (interstitial migration) are distinct and separable phases of monocyte emigration. Furthermore, distinct and separate Ig domains of PECAM are involved in mediating these two steps. PMID:7595204

  7. Control of vascular permeability by adhesion molecules

    PubMed Central

    Sarelius, Ingrid H; Glading, Angela J

    2014-01-01

    Vascular permeability is a vital function of the circulatory system that is regulated in large part by the limited flux of solutes, water, and cells through the endothelial cell layer. One major pathway through this barrier is via the inter-endothelial junction, which is driven by the regulation of cadherin-based adhesions. The endothelium also forms attachments with surrounding proteins and cells via 2 classes of adhesion molecules, the integrins and IgCAMs. Integrins and IgCAMs propagate activation of multiple downstream signals that potentially impact cadherin adhesion. Here we discuss the known contributions of integrin and IgCAM signaling to the regulation of cadherin adhesion stability, endothelial barrier function, and vascular permeability. Emphasis is placed on known and prospective crosstalk signaling mechanisms between integrins, the IgCAMs- ICAM-1 and PECAM-1, and inter-endothelial cadherin adhesions, as potential strategic signaling nodes for multipartite regulation of cadherin adhesion. PMID:25838987

  8. Control of vascular permeability by adhesion molecules.

    PubMed

    Sarelius, Ingrid H; Glading, Angela J

    2015-01-01

    Vascular permeability is a vital function of the circulatory system that is regulated in large part by the limited flux of solutes, water, and cells through the endothelial cell layer. One major pathway through this barrier is via the inter-endothelial junction, which is driven by the regulation of cadherin-based adhesions. The endothelium also forms attachments with surrounding proteins and cells via 2 classes of adhesion molecules, the integrins and IgCAMs. Integrins and IgCAMs propagate activation of multiple downstream signals that potentially impact cadherin adhesion. Here we discuss the known contributions of integrin and IgCAM signaling to the regulation of cadherin adhesion stability, endothelial barrier function, and vascular permeability. Emphasis is placed on known and prospective crosstalk signaling mechanisms between integrins, the IgCAMs- ICAM-1 and PECAM-1, and inter-endothelial cadherin adhesions, as potential strategic signaling nodes for multipartite regulation of cadherin adhesion. PMID:25838987

  9. Adhesions

    MedlinePlus

    ... surfaces so they can shift easily as the body moves. Adhesions cause tissues and organs to stick together. They might connect the loops of the intestines to each other, to nearby ... can occur anywhere in the body. But they often form after surgery on the ...

  10. Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions

    PubMed Central

    1996-01-01

    Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE- cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE- cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen- reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE

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

    PubMed

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

    2013-11-01

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

  12. Brucella abortus as a potential vaccine candidate: induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion molecule 1 surface expression in elutriated human monocytes stimulated by heat-inactivated B. abortus.

    PubMed Central

    Zaitseva, M; Golding, H; Manischewitz, J; Webb, D; Golding, B

    1996-01-01

    Development of a vaccine which is capable of generating a strong cellular immune response associated with gamma interferon (IFN-gamma) production and cytotoxic T-cell development requires that the immunogen be capable of inducing the secretion of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram-negative bacterium Brucella abortus can induce IFN-gamma secretion by T cells. In the present study, we demonstrate that B. abortus and lipopolysaccharide (LPS) from B. abortus can induce IL-12 p40 mRNA expression and protein secretion by human elutriated monocytes (99% pure). p40 mRNA was detected within 4 h, and p40 protein could be measured at 24 h. This induction was abrogated by anti-CD14 monoclonal antibody, suggesting that monocytes recognize B. abortus via their receptor for LPS. The biological activity of IL-12 secreted by B. abortus-stimulated monocytes was demonstrated by its ability to upregulate IFN-gamma mRNA expression in T cells separated from monocytes and B. abortus by a transwell membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity against K562 target cells. B. abortus was shown to rapidly increase the expression of the costimulatory molecules B7.1 and B7.2 and intercellular adhesion molecule 1 on human monocytes. Together, these data indicate that B. abortus can directly activate human monocytes and provide the cytokine milieu which would direct the immune response towards Th1-Tc1 differentiation. PMID:8757841

  13. Novel role of lactosylceramide in vascular endothelial growth factor-mediated angiogenesis in human endothelial cells.

    PubMed

    Rajesh, Mohanraj; Kolmakova, Antonina; Chatterjee, Subroto

    2005-10-14

    Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis associated with coronary heart disease, vascular complications in diabetes, inflammatory vascular diseases, and tumor metastasis. The mechanism of VEGF-driven angiogenesis involving glycosphingolipids such as lactosylceramide (LacCer), however, is not known. To demonstrate the involvement of LacCer in VEGF-induced angiogenesis, we used small interfering RNA (siRNA)-mediated silencing of LacCer synthase expression (GalT-V) in human umbilical vein endothelial cells. This gene silencing markedly inhibited VEGF-induced platelet endothelial cell adhesion molecule-1 (PECAM-1) expression and angiogenesis. Second, we used D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of LacCer synthase and glucosylceramide synthase, that significantly mitigated VEGF-induced PECAM-1 expression and angiogenesis. Interestingly, these phenotypic changes were reversed by LacCer but not by structurally related compounds such as glucosylceramide, digalactosylceramide, and ceramide. In a human mesothelioma cell line (REN) that lacks the endogenous expression of PECAM-1, VEGF/LacCer failed to stimulate PECAM-1 expression and tube formation/angiogenesis. In REN cells expressing human PECAM-1 gene/protein, however, both VEGF and LacCer-induced PECAM-1 protein expression and tube formation/angiogenesis. In fact, VEGF-induced but not LacCer-induced angiogenesis was mitigated by SU-1498, a VEGF receptor tyrosine kinase inhibitor. Also, VEGF/LacCer-induced PECAM-1 expression and angiogenesis was mitigated by protein kinase C and phospholipase A2 inhibitors. These results indicate that LacCer generated in VEGF-treated endothelial cells may serve as an important signaling molecule for PECAM-1 expression and in angiogenesis. This finding and the reagents developed in our report may be useful as anti-angiogenic drugs for further studies in vitro and in vivo. PMID:16151023

  14. Intercellular adhesion molecule-1 concentration, in utero, decreases after antibiotic treatment.

    PubMed

    Hadar, Amnon; Shani-Shrem, Noa; Horowitz, Shulamith

    2005-03-01

    A parturient suffering from preterm premature rupture of membranes at 29-weeks of gestation was hospitalized and staphylococcus was detected in her amniotic fluid. After treatment with antibiotics she delivered a healthy neonate three weeks later. ICAM-1 levels decreased by 20 fold correlating with elimination of the bacteria and prolongation of the pregnancy. PMID:16147830

  15. CCL2 disrupts the adherens junction: implications for neuroinflammation.

    PubMed

    Roberts, Toni K; Eugenin, Eliseo A; Lopez, Lillie; Romero, Ignacio A; Weksler, Babette B; Couraud, Pierre-Olivier; Berman, Joan W

    2012-08-01

    Alterations to blood-brain barrier (BBB) adhesion molecules and junctional integrity during neuroinflammation can promote central nervous system (CNS) pathology. The chemokine CCL2 is elevated during CNS inflammation and is associated with endothelial dysfunction. The effects of CCL2 on endothelial adherens junctions (AJs) have not been defined. We demonstrate that CCL2 transiently induces Src-dependent disruption of human brain microvascular endothelial AJ. β-Catenin is phosphorylated and traffics from the AJ to PECAM-1 (platelet endothelial cell adhesion molecule-1), where it is sequestered at the membrane. PECAM-1 is also tyrosine-phosphorylated, an event associated with recruitment of the phosphatase SHP-2 (Src homology 2 domain-containing protein phosphatase) to PECAM-1, β-catenin release from PECAM-1, and reassociation of β-catenin with the AJ. Surface localization of PECAM-1 is increased in response to CCL2. This may enable the endothelium to sustain CCL2-induced alterations in AJ and facilitate recruitment of leukocytes into the CNS. Our novel findings provide a mechanism for CCL2-mediated disruption of endothelial junctions that may contribute to BBB dysfunction and increased leukocyte recruitment in neuroinflammatory diseases. PMID:22641100

  16. TNF-α and IFN-γ promote lymphocyte adhesion to endothelial junctional regions facilitating transendothelial migration.

    PubMed

    Jaczewska, Justyna; Abdulreda, Midhat H; Yau, Chi Y; Schmitt, Martin M; Schubert, Irene; Berggren, Per-Olof; Weber, Christian; Koenen, Rory R; Moy, Vincent T; Wojcikiewicz, Ewa P

    2014-02-01

    Inflammatory conditions induce redistribution of junctional adhesion receptors toward the apical regions of endothelial cells promoting lymphocyte TEM. Much of the molecular structures of TEM have been revealed; however, the biophysical mechanisms underlying this process remain to be fully elucidated. Here, we used immunofluorescence microscopy and AFM to study endothelial distribution of adhesion molecules upon lymphocyte activation and transmigration. Our immunofluorescence results revealed redistribution of JAM-A and PECAM-1 but not ICAM-1 or VCAM-1 toward the apical junctional regions of HUVECs following a 6-h stimulation with TNF-α and IFN-γ. Consistently, our SCFS studies revealed that Jurkat cell adhesion to stimulated HUVEC monolayers was significantly greater in junctional regions. Enhanced adhesion was mediated mostly by JAM-A receptors. Further AFM adhesion mapping of the homophilic JAM-A/JAM-A interaction on the surfaces of HUVECs revealed a greater number of JAM-A receptors available for binding along junctional regions after TNF-α and IFN-γ stimulation. Our data reveal for the first time that adhesion "hot spots" of JAM-A receptors are involved in initiating lymphocyte TEM under inflammatory conditions. PMID:24072879

  17. TNF-α and IFN-γ promote lymphocyte adhesion to endothelial junctional regions facilitating transendothelial migration

    PubMed Central

    Jaczewska, Justyna; Abdulreda, Midhat H.; Yau, Chi Y.; Schmitt, Martin M.; Schubert, Irene; Berggren, Per-Olof; Weber, Christian; Koenen, Rory R.; Moy, Vincent T.; Wojcikiewicz, Ewa P.

    2014-01-01

    Inflammatory conditions induce redistribution of junctional adhesion receptors toward the apical regions of endothelial cells promoting lymphocyte TEM. Much of the molecular structures of TEM have been revealed; however, the biophysical mechanisms underlying this process remain to be fully elucidated. Here, we used immunofluorescence microscopy and AFM to study endothelial distribution of adhesion molecules upon lymphocyte activation and transmigration. Our immunofluorescence results revealed redistribution of JAM-A and PECAM-1 but not ICAM-1 or VCAM-1 toward the apical junctional regions of HUVECs following a 6-h stimulation with TNF-α and IFN-γ. Consistently, our SCFS studies revealed that Jurkat cell adhesion to stimulated HUVEC monolayers was significantly greater in junctional regions. Enhanced adhesion was mediated mostly by JAM-A receptors. Further AFM adhesion mapping of the homophilic JAM-A/JAM-A interaction on the surfaces of HUVECs revealed a greater number of JAM-A receptors available for binding along junctional regions after TNF-α and IFN-γ stimulation. Our data reveal for the first time that adhesion “hot spots” of JAM-A receptors are involved in initiating lymphocyte TEM under inflammatory conditions. PMID:24072879

  18. HEMCAM, an adhesion molecule expressed by c-kit+ hemopoietic progenitors

    PubMed Central

    1996-01-01

    We have characterized the adhesion molecule HEMCAM, which is expressed by hemopoietic progenitors of embryonic bone marrow. HEMCAM belongs to the immunoglobulin superfamily and consists of the V-V-C2-C2-C2 Ig domains. There are three mRNA splice variants. One has a short cytoplasmic tail; another has a long tail; while the third seems to lack transmembrane and cytoplasmic regions. Except for the NH2-terminal sequence, HEMCAM is identical to gicerin, a molecular involved in neurite outgrowth and Wilm's kidney tumor progression in the chicken and it is significantly homologous with MUC18 a molecule involved in melanoma progression and metastasis in human beings. In the bone marrow the HEMCAM+ cell population contains c-kit+ subsets. HEMCAM+ cells coexpressing the receptor tyrosine kinase c-kit give rise to T cells at a frequency of 0.17 when injected intrathymically in congenic animals. As HEMCAM+, c-kit+ cells differentiate into myeloid and erythroid CFU's the double-positive cell population seems to contain precursors for multiple lineages. HEMCAM promotes cell-cell adhesion of transfected cells. Cross-linking of murine HEMCAM leads to cell spreading of T- lymphocyte progenitors adhering to the vascular adhesion molecules, PECAM-1 and VCAM-1. Thus, HEMCAM is likely to be involved in cellular adhesion and homing processes. PMID:8978830

  19. Soluble adhesion molecules correlate with surface expression in an in vitro model of endothelial activation.

    PubMed

    Kjaergaard, Anders G; Dige, Anders; Krog, Jan; Tønnesen, Else; Wogensen, Lise

    2013-10-01

    Endothelial activation is a pivotal event in the development and progression of inflammation. Central to endothelial activation is the up-regulation of cellular adhesion molecules (CAMs) including E-selectin (CD62E), ICAM-1 (CD54), VCAM-1 (CD106) and PECAM-1 (CD31). These CAMs are also found in soluble forms (sCAMs). In this in vitro study of endothelial activation, we examined whether the levels of sCAMs correlate with the endothelial surface expression of CAMs in a dose-dependent and time-dependent manner. Such a correlation would support the use of sCAMs as surrogate markers for endothelial activation in inflammatory conditions. Human umbilical vein endothelial cells (HUVEC) were cultured with various concentrations of TNF-α for 8 hr and at a fixed concentration of TNF-α for various durations. The levels of soluble and surface-bound E-selectin, ICAM-1, VCAM-1 and PECAM-1 were quantified by flow cytometry. TNF-α stimulation increased CAM and sCAM expression in a dose-dependent and time-dependent manner. There was a significant positive correlation between the levels of ICAM-1 and sICAM-1 and between the levels of VCAM and sVCAM-1 in both the dose-response and time-response experiments. A positive correlation between the levels of E-selectin and sE-selectin was observed in the time-response experiment. This study supports the use of sCAMs as potential biomarkers of endothelial activation. In particular, the use of sICAM-1, sVCAM-1 and sE-selectin seems promising.

  20. VE-cadherin is a critical molecule for trophoblast-endothelial cell interaction in decidual spiral arteries

    SciTech Connect

    Bulla, Roberta; Villa, Antonello; Bossi, Fleur; Cassetti, Arianna; Radillo, Oriano; Spessotto, Paola; De Seta, Francesco; Guaschino, Secondo; Tedesco, Francesco . E-mail: tedesco@univ.trieste.it

    2005-02-01

    Fetal cytotrophoblasts colonize the decidual spiral arteries during pregnancy and partially replace the endothelium by an as yet unknown mechanism. To clarify this issue, we cocultured trophoblast cells (TCs) and decidual endothelial cells (DECs) isolated from first trimester placentae and found by electron microscopic analysis that TCs adhered to DECs and migrated through the interendothelial junctions within 24 h. Since extravillous TCs were shown by FACS analysis to express vascular-endothelial (VE)-cadherin and platelet endothelial cell adhesion molecule-1 (PECAM)-1, we investigated the role of these junctional molecules in TC adhesion to DECs and transendothelial migration of cytotrophoblasts. Both VE-cadherin and PECAM-1 were present at the contact sites between TCs and DECs in decidual sections. TC adhesion and migration were markedly inhibited by mAbs to VE-cadherin and marginally by mAb to PECAM-1. Increased expression of VE-cadherin was observed at the contact areas between TCs and DECs, whereas PECAM-1 was found to be redistributed from intercellular junctions. The induction of apoptosis of DECs by TCs, as the mechanism responsible for their replacement, was ruled out by the negative staining with TUNEL of DECs cocultured with TCs and the absence of DNA fragmentation. In conclusion, VE-cadherin is involved in transendothelial migration of TCs, and replacement of DECs by TCs is not the result of apoptosis.

  1. Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells

    PubMed Central

    Collins, Caitlin; Osborne, Lukas D.; Guilluy, Christophe; Chen, Zhongming; O’Brien, E Tim; Reader, John S.; Burridge, Keith; Superfine, Richard; Tzima, Ellie

    2014-01-01

    Endothelial cell (ECs) lining blood vessels express many mechanosensors, including platelet endothelial cell adhesion molecule-1 (PECAM-1), that convert mechanical force to biochemical signals. While it is accepted that mechanical stresses and the mechanical properties of ECs regulate vessel health, the relationship between force and biological response remains elusive. Here we show that ECs integrate mechanical forces and extracellular matrix (ECM) cues to modulate their own mechanical properties. We demonstrate that the ECM influences EC response to tension on PECAM-1. ECs adherent on collagen display divergent stiffening and focal adhesion growth compared to ECs on fibronectin. This is due to PKA-dependent serine phosphorylation and inactivation of RhoA. PKA signaling regulates focal adhesion dynamics and EC compliance in response to shear stress in vitro and in vivo. Our study identifies a ECM-specific, mechanosensitive signaling pathway that regulates EC compliance and may serve as an atheroprotective mechanism maintains blood vessel integrity in vivo. PMID:24917553

  2. Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells.

    PubMed

    Collins, Caitlin; Osborne, Lukas D; Guilluy, Christophe; Chen, Zhongming; O'Brien, E Tim; Reader, John S; Burridge, Keith; Superfine, Richard; Tzima, Ellie

    2014-06-11

    Endothelial cells (ECs) lining blood vessels express many mechanosensors, including platelet endothelial cell adhesion molecule-1 (PECAM-1), that convert mechanical force into biochemical signals. While it is accepted that mechanical stresses and the mechanical properties of ECs regulate vessel health, the relationship between force and biological response remains elusive. Here we show that ECs integrate mechanical forces and extracellular matrix (ECM) cues to modulate their own mechanical properties. We demonstrate that the ECM influences EC response to tension on PECAM-1. ECs adherent on collagen display divergent stiffening and focal adhesion growth compared with ECs on fibronectin. This is because of protein kinase A (PKA)-dependent serine phosphorylation and inactivation of RhoA. PKA signalling regulates focal adhesion dynamics and EC compliance in response to shear stress in vitro and in vivo. Our study identifies an ECM-specific, mechanosensitive signalling pathway that regulates EC compliance and may serve as an atheroprotective mechanism that maintains blood vessel integrity in vivo.

  3. Effect of various metals on intercellular adhesion molecule-1 expression and tumour necrosis factor alpha production by normal human keratinocytes.

    PubMed

    Guéniche, A; Viac, J; Lizard, G; Charveron, M; Schmitt, D

    1994-01-01

    Nickel, cobalt and chromium are metals very often implicated in allergic contact dermatitis. In vivo, keratinocytes, which are the first target cells, can be directly activated to participate in the local reaction, especially through the expression of the membrane antigen ICAM-1, a ligand of the leucocyte antigen LFA-1, and the production of cytokines. Our aim was to assess the effects of sensitizing metal haptens (nickel, cobalt and chromium) compared with the toxic metal cadmium on the induction of ICAM-1 and the production of TNF alpha by epidermal cells. For this purpose, normal human keratinocytes obtained during plastic skin surgery were cultured in low-calcium defined medium (MCDB153) and the metals were used in non-toxic concentrations. Using FACS analysis, ICAM-1 expression was found to be induced only by nickel. This stimulation appeared as early as 24 h after stimulation. All the metals induced a low expression of TNF alpha detectable by immunocytochemistry correlating with the induction of the nuclear stress protein Hsp72 which is closely linked genetically with the TNF alpha locus. However, only Ni2+, Co2+ and Cr2+ induced a significant release of TNF alpha detectable by ELISA after 48 h stimulation. This secretion was lower than that observed with known stimulants such as lipopolysaccharide. These results indicate that the metals studied are able to induce an aggressive cellular effect, and that nickel, by its ICAM-1 induction, may play a major role in the keratinocyte activation state during allergic contact dermatitis. PMID:7864660

  4. Bile acid signaling through FXR induces intracellular adhesion molecule-1 expression in mouse liver and human hepatocytes.

    PubMed

    Qin, Pu; Borges-Marcucci, Lisa A; Evans, Mark J; Harnish, Douglas C

    2005-08-01

    Previous studies have demonstrated a dramatic induction of inflammatory gene expression in livers from mice fed a high-fat, high-cholesterol diet containing cholate after 3-5 wk. To determine the contribution of cholate in mediating these inductions, C57BL/6 mice were fed a chow diet supplemented with increasing concentrations of cholic acid (CA) for 5 days. A dose-dependent induction in the hepatic levels of TNF-alpha, VCAM-1, ICAM-1, and SAA-2 mRNA were observed. As positive controls, a dose-dependent repression of cholesterol 7alpha-hydroxylase and a dose-dependent induction of small heterodimer partner (SHP) expression were also observed, suggesting that farnesoid X receptor (FXR) was activated. In addition, ICAM-1 and SHP mRNA levels were also induced in primary human hepatocytes when treated with chenodeoxycholic acid or GW4064, a FXR-selective agonist. The involvement of FXR in CA-induced inflammatory gene expression was further investigated in the human hepatic cell line HepG2. Both ICAM-1 and SHP expression were induced in a dose- and time-dependent manner by treatment with the FXR-selective agonist GW4064. Moreover, the induction of ICAM-1 by GW4064 was inhibited by the FXR antagonist guggulsterone or with transfection of FXR siRNA. Finally, the activity of FXR was mapped to a retinoic acid response element (RARE) site containing an imbedded farnesoid X response element (FXRE) on the human ICAM-1 promoter and FXR and retinoid X receptor were demonstrated to bind to this site. Finally, FXR-mediated activation of ICAM-1 could be further enhanced by TNF-alpha cotreatment in hepatocytes, suggesting a potential cooperation between cytokine and bile acid-signaling pathways during hepatic inflammatory events.

  5. Interleukin-6 and intercellular cell adhesion molecule-1 expression remains elevated in revived live endothelial cells following spaceflight.

    PubMed

    Muid, S; Froemming, G R A; Ali, A M; Nawawi, H

    2013-12-01

    The effects of spaceflight on cardiovascular health are not necessarily seen immediately after astronauts have returned but can be delayed. It is important to investigate the long term effects of spaceflight on protein and gene expression of inflammation and endothelial activation as a predictor for the development of atherosclerosis and potential cardiovascular problems. The objectives of this study were to investigate the (a) protein and gene expression of inflammation and endothelial activation, (b) expression of nuclear factor kappa B (NFκB), signal transducer and activator of transcription-3 (STAT-3) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC) 3 months post-space flight travel compared to ground controls. HUVEC cultured on microcarriers in fluid processing apparatus were flown to the International Space Station (ISS) by the Soyuz TMA-11 rocket. After landing, the cells were detached from microcarriers and recultured in T-25 cm(2) culture flasks (Revived HUVEC). Soluble protein expression of IL-6, TNF-α, ICAM-1, VCAM-1 and e-selectin were measured by ELISA. Gene expression of these markers and in addition NFκB, STAT-3 and eNOS were measured. Spaceflight induced IL-6 and ICAM-1 remain elevated even after 3 months post spaceflight travel and this is mediated via STAT-3 pathway. The downregulation of eNOS expression in revived HUVEC cells suggests a reduced protection of the cells and the surrounding vessels against future insults that may lead to atherosclerosis. It would be crucial to explore preventive measures, in relation to atherosclerosis and its related complications.

  6. Adhesive plasters

    DOEpatents

    Holcombe, Jr., Cressie E.; Swain, Ronald L.; Banker, John G.; Edwards, Charlene C.

    1978-01-01

    Adhesive plaster compositions are provided by treating particles of Y.sub.2 O.sub.3, Eu.sub.2 O.sub.3, Gd.sub.2 O.sub.3 or Nd.sub.2 O.sub.3 with dilute acid solutions. The resulting compositions have been found to spontaneously harden into rigid reticulated masses resembling plaster of Paris. Upon heating, the hardened material is decomposed into the oxide, yet retains the reticulated rigid structure.

  7. Impact of simulated microgravity on the secretory and adhesive activity of cultured human vascular endothelial cells.

    NASA Astrophysics Data System (ADS)

    Rudimov, Evgeny; Buravkova, Ludmila; Pogodina, Margarita; Andrianova, Irina

    The layer of vascular endothelial cells (ECs) is a dynamic,disseminated organ that perform the function of an interface between the blood and vascular wall. The endothelial monolayer is able to quickly respond to changes in the microenvironment due to its synthesis of vasoactive substances, chemokines, adhesion molecules expression, etc. ECs are highly sensitive to gravitational changes and capable of short-term and long-term responses (Sangha et al., 2001; Buravkova et al., 2005; Infanger et al., 2006, 2007. However, the question remains how to reflect the impact of microgravity on endothelium under the inflammatory process. Therefore, the aim of this study was to investigate secretory and adhesive activity of human umbilical vein endothelial cells (HUVECs) during simulated microgravity and TNF-a activation. HUVECs were isolated according to Gimbrone et al. (1978) in modification A. Antonov (1981) and used for experiments at 2-4 passages. HUVECs were activated by low level of TNF-a (2 ng/ml). Microgravity was generated by Random Positioning Machine (RPM, Dutch Space, Leiden) placed into the thermostat at 37°C. After 24 hours of clinorotation we measured adhesion molecules expression on the cell surface (ICAM-1, VCAM-1, PECAM-1, E-selectin, CD144, endoglin (CD105)) and cell viability using a flow cytometry. To evaluate the level of target gene expression was used the real time RT-PCR. IL-6 and IL-8 concentration was measured in the conditioned medium of HUVECs by using the ELISA test. We found that simulated microgravity within 24 hours caused a decrease of ICAM-1, CD144, and E-selectin expression, at the same time not affect the cell viability, endoglin and PECAM-1 expression on the surface HUVEC. Furthermore, there were no changes of the level of IL-6 and IL-8 gene expression and their products in the culture medium. TNF-activated HUVECs showed an increase in gene expression of interleukins and molecules involved in the adhesion process, which also was confirmed

  8. Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart and kidney microvasculature in spontaneously hypertensive rats.

    PubMed

    Tayebati, Seyed Khosrow; Tomassoni, Daniele; Di Cesare Mannelli, Lorenzo; Amenta, Francesco

    2016-01-01

    Endothelial cells represent an important vascular site of signaling and development of damage during ischemia, inflammation and other pathological conditions. Excessive reactive oxygen species production causes pathological activation of endothelium including exposure of cell to adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells. These molecules represent important markers of endothelial inflammation. The present study was designed to investigate, with immunochemical and immunohistochemical techniques, the effect of treatment with (+/-)-alpha lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an increased oxidative stress status in the heart characterized by thiobarbituric acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher oxidative stress also modifies adhesion molecules expression. In the heart VCAM-1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1 and PECAM-1 expression was significantly greater in the renal endothelium of SHR. (+/-)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly decreased TBARS levels, the nucleic acid oxidation and prevented adhesion molecules expression in cardiac and renal vascular endothelium. These data suggest that endothelial molecules may be used for studying the mechanisms of vascular injury on target organs of hypertension. The effects observed after treatment with (+)-alpha lipoic acid could open new perspectives for countering heart and kidney microvascular injury which represent a common feature in hypertensive end-organs damage.

  9. Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart and kidney microvasculature in spontaneously hypertensive rats.

    PubMed

    Tayebati, Seyed Khosrow; Tomassoni, Daniele; Di Cesare Mannelli, Lorenzo; Amenta, Francesco

    2016-01-01

    Endothelial cells represent an important vascular site of signaling and development of damage during ischemia, inflammation and other pathological conditions. Excessive reactive oxygen species production causes pathological activation of endothelium including exposure of cell to adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells. These molecules represent important markers of endothelial inflammation. The present study was designed to investigate, with immunochemical and immunohistochemical techniques, the effect of treatment with (+/-)-alpha lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an increased oxidative stress status in the heart characterized by thiobarbituric acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher oxidative stress also modifies adhesion molecules expression. In the heart VCAM-1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1 and PECAM-1 expression was significantly greater in the renal endothelium of SHR. (+/-)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly decreased TBARS levels, the nucleic acid oxidation and prevented adhesion molecules expression in cardiac and renal vascular endothelium. These data suggest that endothelial molecules may be used for studying the mechanisms of vascular injury on target organs of hypertension. The effects observed after treatment with (+)-alpha lipoic acid could open new perspectives for countering heart and kidney microvascular injury which represent a common feature in hypertensive end-organs damage. PMID:26207883

  10. Chinese Herbal Cardiotonic Pill Stabilizes Vulnerable Plaques in Rabbits by Decreasing the Expression of Adhesion Molecules

    PubMed Central

    Chen, Liang; Li, Xiaonan; Li, Changjiang; Rong, Yuanyuan; Xiao, Yawei; Xu, Xinsheng; Yao, Guihua; Jiang, Guihua

    2016-01-01

    Abstract: The cardiotonic pill (CP), consisting of a mixture of Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, has been widely used in the prevention and treatment of cardiovascular disease. Adhesion molecules, including intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, are involved in the development of vulnerable plaque. We investigated the effect of the CP in a rabbit model of vulnerable plaque established by local transfection with p53 gene. Compared with the control group, rabbits with vulnerable plaque showed a significantly lower intima-media thickness and plaque burden after CP treatment for 12 weeks. Moreover, the reduction in rate of plaque rupture and vulnerability index was similar. On enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry analysis, the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited with CP treatment. CP treatment could postpone atherosclerotic plaque development and stabilize vulnerable plaque by inhibiting the expression of adhesion molecules in treatment of cardiovascular disease. PMID:27110743

  11. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    PubMed

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2016-02-01

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  12. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    PubMed

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2015-12-04

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  13. Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion.

    PubMed

    Abe, Y; El-Masri, B; Kimball, K T; Pownall, H; Reilly, C F; Osmundsen, K; Smith, C W; Ballantyne, C M

    1998-05-01

    Hypertriglyceridemia may contribute to the development of atherosclerosis by increasing expression of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as markers for CAMs. In this study, we examined the association between sCAMs and other risk factors occurring with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels, and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhesion in vitro. Compared with normal control subjects (n=20), patients with hypertriglyceridemia and low HDL (n=39) had significantly increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316+/-28.8 versus 225+/-16.6 ng/mL), sVCAM-1 (743+/-52.2 versus 522+/-43.6 ng/mL), and soluble E-selectin (83+/-5.9 versus 49+/-3.6 ng/mL). ANCOVA showed that the higher sCAM levels in patients occurred independently of diabetes mellitus and other risk factors. In 27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for > or =7 months, triglyceride level was reduced by 47+/-4.6%, sICAM-1 level was reduced by 9+/-3.4% (P=.02), and soluble E-selectin level was reduced by 16+/-3.2% (P<.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that disorders in triglyceride and HDL metabolism influence CAM expression and treatment with fish oils may alter vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1 at the concentration seen in patients significantly inhibited adhesion of monocytes to interleukin-1-stimulated cultured endothelial cells under conditions of flow by 27.5+/-7.2%. Thus, elevated sCAMs may negatively regulate monocyte adhesion.

  14. Thermal Characterization of Adhesive

    NASA Technical Reports Server (NTRS)

    Spomer, Ken A.

    1999-01-01

    The current Space Shuttle Reusable Solid Rocket Motor (RSRM) nozzle adhesive bond system is being replaced due to obsolescence. Down-selection and performance testing of the structural adhesives resulted in the selection of two candidate replacement adhesives, Resin Technology Group's Tiga 321 and 3M's EC2615XLW. This paper describes rocket motor testing of these two adhesives. Four forty-pound charge motors were fabricated in configurations that would allow side by side comparison testing of the candidate replacement adhesives and the current RSRM adhesives. The motors provided an environment where the thermal performance of adhesives in flame surface bondlines was compared. Results of the FPC testing show that: 1) The phenolic char depths on radial bond lines is approximately the same and vary depending on the position in the blast tube regardless of which adhesive was used; 2) The adhesive char depth of the candidate replacement adhesives is less than the char depth of the current adhesives; 3) The heat-affected depth of the candidate replacement adhesives is less than the heat-affected depth of the current adhesives; and 4) The ablation rates for both replacement adhesives are slower than that of the current adhesives.

  15. Understanding Marine Mussel Adhesion

    PubMed Central

    Roberto, Francisco F.

    2007-01-01

    In addition to identifying the proteins that have a role in underwater adhesion by marine mussels, research efforts have focused on identifying the genes responsible for the adhesive proteins, environmental factors that may influence protein production, and strategies for producing natural adhesives similar to the native mussel adhesive proteins. The production-scale availability of recombinant mussel adhesive proteins will enable researchers to formulate adhesives that are water-impervious and ecologically safe and can bind materials ranging from glass, plastics, metals, and wood to materials, such as bone or teeth, biological organisms, and other chemicals or molecules. Unfortunately, as of yet scientists have been unable to duplicate the processes that marine mussels use to create adhesive structures. This study provides a background on adhesive proteins identified in the blue mussel, Mytilus edulis, and introduces our research interests and discusses the future for continued research related to mussel adhesion. PMID:17990038

  16. Understanding Marine Mussel Adhesion

    SciTech Connect

    H. G. Silverman; F. F. Roberto

    2007-12-01

    In addition to identifying the proteins that have a role in underwater adhesion by marine mussels, research efforts have focused on identifying the genes responsible for the adhesive proteins, environmental factors that may influence protein production, and strategies for producing natural adhesives similar to the native mussel adhesive proteins. The production-scale availability of recombinant mussel adhesive proteins will enable researchers to formulate adhesives that are waterimpervious and ecologically safe and can bind materials ranging from glass, plastics, metals, and wood to materials, such as bone or teeth, biological organisms, and other chemicals or molecules. Unfortunately, as of yet scientists have been unable to duplicate the processes that marine mussels use to create adhesive structures. This study provides a background on adhesive proteins identified in the blue mussel, Mytilus edulis, and introduces our research interests and discusses the future for continued research related to mussel adhesion.

  17. Quantitative Glycoproteomic Analysis Identifies Platelet-Induced Increase of Monocyte Adhesion via the Up-Regulation of Very Late Antigen 5.

    PubMed

    Huang, Jiqing; Kast, Juergen

    2015-08-01

    Physiological stimuli, such as thrombin, or pathological stimuli, such as lysophosphatidic acid (LPA), activate platelets circulating in blood. Once activated, platelets bind to monocytes via P-selectin-PSGL-1 interactions but also release the stored contents of their granules. These platelet releasates, in addition to direct platelet binding, activate monocytes and facilitate their recruitment to atherosclerotic sites. Consequently, understanding the changes platelet releasates induce in monocyte membrane proteins is critical. We studied the glyco-proteome changes of THP-1 monocytic cells affected by LPA- or thrombin-induced platelet releasates. We employed lectin affinity chromatography combined with filter aided sample preparation to achieve high glyco- and membrane protein and protein sequence coverage. Using stable isotope labeling by amino acids in cell culture, we quantified 1715 proteins, including 852 membrane and 500 glycoproteins, identifying the up-regulation of multiple proteins involved in monocyte extracellular matrix binding and transendothelial migration. Flow cytometry indicated expression changes of integrin α5, integrin β1, PECAM-1, and PSGL-1. The observed increase in monocyte adhesion to fibronectin was determined to be mediated by the up-regulation of very late antigen 5 via a P-selectin-PSGL-1 independent mechanism. This novel aspect could be validated on CD14+ human primary monocytes, highlighting the benefits of the improved enrichment method regarding high membrane protein coverage and reliable quantification. PMID:26159767

  18. PH dependent adhesive peptides

    DOEpatents

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  19. Kidney injury molecule-1 (KIM-1) mediates renal epithelial cell repair via ERK MAPK signaling pathway

    PubMed Central

    Zhang, Zhiwei; Cai, Cindy X

    2016-01-01

    The expression of kidney injury molecule-1 (KIM-1), a very promising sensitive and specific urinary biomarker for acute renal injury, is markedly upregulated in injured and regenerating renal proximal tubular epithelial cells following ischemic or toxic insults, suggesting a possible role for this molecule in renal repair process. In the present study we report that expression of KIM-1 facilitates renal tubular epithelial cell repair by promoting cell migration and proliferation. KIM-1 expression also enhances ERK MAPK activation, and the modulatory effect of KIM-1 on cellular repair process is likely mediated via ERK MAPK signaling pathway. PMID:27084535

  20. Mini-review: barnacle adhesives and adhesion.

    PubMed

    Kamino, Kei

    2013-01-01

    Barnacles are intriguing, not only with respect to their importance as fouling organisms, but also in terms of the mechanism of underwater adhesion, which provides a platform for biomimetic and bioinspired research. These aspects have prompted questions regarding how adult barnacles attach to surfaces under water. The multidisciplinary and interdisciplinary nature of the studies makes an overview covering all aspects challenging. This mini-review, therefore, attempts to bring together aspects of the adhesion of adult barnacles by looking at the achievements of research focused on both fouling and adhesion. Biological and biochemical studies, which have been motivated mainly by understanding the nature of the adhesion, indicate that the molecular characteristics of barnacle adhesive are unique. However, it is apparent from recent advances in molecular techniques that much remains undiscovered regarding the complex event of underwater attachment. Barnacles attached to silicone-based elastomeric coatings have been studied widely, particularly with respect to fouling-release technology. The fact that barnacles fail to attach tenaciously to silicone coatings, combined with the fact that the mode of attachment to these substrata is different to that for most other materials, indicates that knowledge about the natural mechanism of barnacle attachment is still incomplete. Further research on barnacles will enable a more comprehensive understanding of both the process of attachment and the adhesives used. Results from such studies will have a strong impact on technology aimed at fouling prevention as well as adhesion science and engineering.

  1. Effect of Linomide on adhesion molecules, TNF-alpha, nitrogen oxide, and cell adhesion.

    PubMed

    Abdul-Hai, A; Hershkoviz, R; Weiss, L; Lider, O; Slavin, S

    2005-02-01

    Linomide (quinoline-3-carboxamide) is an immunomodulator with anti-inflammatory effects in rodents with autoimmune diseases. Its mode of action still remains to be elucidated. We hypothesized that an investigation of T cell interactions with the extracellular matrix (ECM), composed of glycoproteins such as fibronectin (FN) and laminin (LN), might provide better understanding of their in vivo mode of action in extravascular inflammatory sites. We examined the effect of Linomide on T cell adhesion to intact ECM, and separately to LN, and FN, and on the release and production of tumor necrosis factor (TNFalpha) and nitrogen oxide (NO) in relation to adhesive molecules in non-obese diabetic (NOD) female spleen cells, focusing on intracellular adhesion molecule-1 (ICAM-1) and CD44. NOD female mice that developed spontaneous autoimmune insulitis, which destroys pancreatic islets and subsequently leads to insulin-deficient diabetes mellitus, were studied. Linomide, given in the drinking water or added to tissue cultures in vitro, inhibited the beta1 integrin-mediated adhesion of T cells to ECM, FN and LN, as well as the production and release of TNFalpha and NO, which play a major role in the induction and propagation of T cell-mediated insulitis. In addition, exposure of T cells to Linomide resulted in increased expression of CD44 and ICAM-1 molecules on spleen cells of Linomide-treated mice; such an increase in adhesion molecule expression may lead to more effective arrest of T cell migration in vivo. The regulation of T-cell adhesion, adhesion receptor expression, and inhibition of TNFalpha and NO secretion by Linomide may explain its beneficial role and provide a new tool for suppressing self-reactive T cell-dependent autoimmune diseases. PMID:15652754

  2. White blood cell deformation and firm adhesion

    NASA Astrophysics Data System (ADS)

    Szatmary, Alex; Eggleton, Charles

    2011-11-01

    For a white blood cell (WBC) to arrive at infection sites, it forms chemical attachments with activated endothelial cells. First, it bonds with P-selectin, which holds it to the wall, but weakly; this allows the WBC to roll under the shear flow of the blood around it. Later, the WBCs bond with the stronger intracellular adhesion molecule-1 (ICAM-1); it is these ICAM bonds that allow the WBCs to fully resist the flow and stop rolling, allowing them to crawl through the endothelial wall. We model this numerically. Our model uses the immersed boundary method to represent the interaction of the shear flow with the deformable cell membrane. Receptors are on the tips of microvilli-little fingers sticking off of the cell membrane. The microvilli also deform. The receptors stochastically form and break bonds with molecules on the wall. Using this method, the history of each microvillus and its bonds can be found, as well as the distribution of the adhesion traction forces and how all of these vary with the deformability of the white blood cell. At higher shear rates, the white blood cell membrane deforms more, increasing its contact area with the surface; this effect is larger for softer membranes. We investigate how the deformability of the WBC affects the ease with which it forms firm adhesion.

  3. Critical roles of co-activation receptor DNAX accessory molecule-1 in natural killer cell immunity

    PubMed Central

    Xiong, Peng; Sang, Hai-Wei; Zhu, Min

    2015-01-01

    Natural killer (NK) cells, which can exert early and powerful anti-tumour and anti-viral responses, are important components of the innate immune system. DNAX accessory molecule-1 (DNAM-1) is an activating receptor molecule expressed on the surface of NK cells. Recent findings suggest that DNAM-1 is a critical regulator of NK cell biology. DNAM-1 is involved in NK cell education and differentiation, and also plays a pivotal role in the development of cancer, viral infections and immune-related diseases. However, tumours and viruses have developed multiple mechanisms to evade the immune system. They are able to impair DNAM-1 activity by targeting the DNAM-1 receptor–ligand system. We have reviewed the roles of DNAM-1, and its biological functions, with respect to NK cell biology and DNAM-1 chimeric antigen receptor-based immunotherapy. PMID:26235210

  4. Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

    PubMed

    Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

    2015-08-27

    Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner.

  5. Adhesion at metal interfaces

    NASA Technical Reports Server (NTRS)

    Banerjea, Amitava; Ferrante, John; Smith, John R.

    1991-01-01

    A basic adhesion process is defined, the theory of the properties influencing metallic adhesion is outlined, and theoretical approaches to the interface problem are presented, with emphasis on first-principle calculations as well as jellium-model calculations. The computation of the energies of adhesion as a function of the interfacial separation is performed; fully three-dimensional calculations are presented, and universality in the shapes of the binding energy curves is considered. An embedded-atom method and equivalent-crystal theory are covered in the framework of issues involved in practical adhesion.

  6. Gecko adhesion: evolutionary nanotechnology.

    PubMed

    Autumn, Kellar; Gravish, Nick

    2008-05-13

    If geckos had not evolved, it is possible that humans would never have invented adhesive nanostructures. Geckos use millions of adhesive setae on their toes to climb vertical surfaces at speeds of over 1ms-1. Climbing presents a significant challenge for an adhesive in requiring both strong attachment and easy rapid removal. Conventional pressure-sensitive adhesives (PSAs) are either strong and difficult to remove (e.g. duct tape) or weak and easy to remove (e.g. sticky notes). The gecko adhesive differs dramatically from conventional adhesives. Conventional PSAs are soft viscoelastic polymers that degrade, foul, self-adhere and attach accidentally to inappropriate surfaces. In contrast, gecko toes bear angled arrays of branched, hair-like setae formed from stiff, hydrophobic keratin that act as a bed of angled springs with similar effective elastic modulus to that of PSAs. Setae are self-cleaning and maintain function for months during repeated use in dirty conditions. Setae are an anisotropic 'frictional adhesive' in that adhesion requires maintenance of a proximally directed shear load, enabling either a tough bond or spontaneous detachment. Gecko-like synthetic adhesives may become the glue of the future-and perhaps the screw of the future as well.

  7. Electro-dry-adhesion.

    PubMed

    Krahn, Jeffrey; Menon, Carlo

    2012-03-27

    This work presents novel conductive bioinspired dry adhesives with mushroom caps that enable the use of a synergistic combination of electrostatic and van der Waals forces (electro-dry-adhesion). An increase in shear adhesion bond strength of up to 2046% on a wide range of materials is measured when a maximum electrical field of 36.4 V μm(-1) is applied. A suction effect, due to the shape of the dry adhesive fibers, on overall adhesion was not noted for electro-dry-adhesives when testing was performed at both atmospheric and reduced pressure. Utilization of electrostatics to apply a preloading force to dry adhesive fiber arrays allows increased adhesion even after electrostatic force generation has been halted by ensuring the close contact necessary for van der Waals forces to be effective. A comparison is made between self-preloading of the electro-dry-adhesives and the direct application of a normal preloading pressure resulting in nearly the same shear bond strength with an applied voltage of 3.33 kV on the same sample.

  8. Electro-dry-adhesion.

    PubMed

    Krahn, Jeffrey; Menon, Carlo

    2012-03-27

    This work presents novel conductive bioinspired dry adhesives with mushroom caps that enable the use of a synergistic combination of electrostatic and van der Waals forces (electro-dry-adhesion). An increase in shear adhesion bond strength of up to 2046% on a wide range of materials is measured when a maximum electrical field of 36.4 V μm(-1) is applied. A suction effect, due to the shape of the dry adhesive fibers, on overall adhesion was not noted for electro-dry-adhesives when testing was performed at both atmospheric and reduced pressure. Utilization of electrostatics to apply a preloading force to dry adhesive fiber arrays allows increased adhesion even after electrostatic force generation has been halted by ensuring the close contact necessary for van der Waals forces to be effective. A comparison is made between self-preloading of the electro-dry-adhesives and the direct application of a normal preloading pressure resulting in nearly the same shear bond strength with an applied voltage of 3.33 kV on the same sample. PMID:22397643

  9. Reversible Thermoset Adhesives

    NASA Technical Reports Server (NTRS)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  10. Hyperbaric oxygen treatment reduces neutrophil-endothelial adhesion in chronic wound conditions through S-nitrosation.

    PubMed

    Kendall, Alexandra C; Whatmore, Jacqueline L; Winyard, Paul G; Smerdon, Gary R; Eggleton, Paul

    2013-01-01

    Hyperbaric oxygen (HBO) therapy is an effective treatment for diabetic chronic wounds. HBO reduces inflammation and accelerates wound healing, by mechanisms that remain unclear. Here we examined a mechanism by which HBO may reduce neutrophil recruitment, through changes in endothelial and neutrophil adhesion molecule expression and function. Human umbilical vein endothelial cells and neutrophils were exposed to selected chronic wound conditions, comprising hypoxia in the presence of lipopolysaccharide and tumor necrosis factor-alpha, and then treated with HBO. We observed neutrophil adhesion to endothelial cells following treatment with chronic wound conditions, which was reversed by HBO treatment. This was partly explained by reduced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by HBO. No changes in neutrophil adhesion molecule expression (CD18, CD11b, CD62L, CD31) were observed following HBO treatment. However, HBO decreased hydrogen peroxide generation by neutrophils, and induced nitrous oxide-related protein modifications. The transnitrosating agent S-nitroso-L-cysteine ethyl ester (600 μM) also reduced neutrophil adhesion to human umbilical vein endothelial cell monolayers, and the iNOS inhibitor 1400 W (10 μM) and HgCl2, which promotes the decomposition of S-nitrosothiols (1 mM), reversed the effect of HBO, suggesting that S-nitrosation may inhibit neutrophil-endothelial cell adhesion. This study indicates that HBO could reduce inflammation in wounds through reduced neutrophil recruitment, mediated by S-nitrosation. PMID:24134224

  11. Neuron adhesion and strengthening

    NASA Astrophysics Data System (ADS)

    Rocha, Aracely; Jian, Kuihuan; Ko, Gladys; Liang, Hong

    2010-07-01

    Understanding the neuron/material adhesion is important for neuron stimulation and growth. The current challenges remain in the lack of precision of measuring techniques and understanding the behavior of neuron. Here, we report a fluid shear method to investigate adhesion at the neuron/poly-D-lysine interface. In this study, the adhesion of 12-day-old chick embryo-retina neurons cultured on poly-D-lysine coated glass coverslips was measured via parallel disk rotational flow. The shear stress experienced by the cells increases with the disk radius. There is a critical point along the radius (Rc) where the stress experienced by the neurons equals their adhesion. The measured Rc can be used to calculate the neuron adhesion. Our results demonstrate that neurons adhered to the poly-D-lysine had a strain hardening effect. The adhesive shear stress of the neuron-material increased with applied shear (τa). When the τa reached or exceeded the value of 40 dyn/cm2, the adhesion remained constant at approximately 30 dyn/cm2. The present work allowed us not only to quantify the adhesive strength and force but also to evaluate the value of strain hardening at the neuron/poly-D-lysine interface.

  12. Postoperative Peritoneal Adhesions

    PubMed Central

    Ryan, Graeme B.; Grobéty, Jocelyne; Majno, Guido

    1971-01-01

    This paper describes an experimental model of peritoneal adhesions, in the rat, based on two relatively minor accidents that may occur during abdominal surgery in man: drying of the serosa, and bleeding. Drying alone had little effect; drying plus bleeding consistently produced adhesions to the dried area. Fresh blood alone produced adhesions between the three membranous structures [omentum and pelvic fat bodies (PFBs)]. The formation of persistent adhesions required whole blood. Preformed clots above a critical size induced adhesions even without previous serosal injury; they were usually captured by the omentum and PFBs. If all three membranous structures were excised, the clots caused visceral adhesions. The protective role of the omentum, its structure, and the mechanism of omental adhesions, are discussed. These findings are relevant to the pathogenesis of post-operative adhesions in man. ImagesFig 3Fig 4Fig 5Fig 6Fig 7Fig 12Fig 13Fig 1Fig 2Fig 14Fig 15Fig 8Fig 9Fig 10Fig 11 PMID:5315369

  13. Instant acting adhesive system

    NASA Technical Reports Server (NTRS)

    Davis, T. R.; Haines, R. C.

    1971-01-01

    Adhesive developes 80 percent of minimum bond strength of 250 psi less than 30 sec after activation is required. Adhesive is stable, handles easily, is a low toxic hazard, and is useful in industrial and domestic prototype bonding and clamping operations.

  14. Adhesives in larynx repair.

    PubMed

    Lyons, M B; Lyons, G D; Webster, D; Wheeler, V R

    1989-04-01

    Guinea pig laryngeal fractures were used as a model to compare the ease of application and effectiveness of the fibrinogen-adhesive system with the ease of application and effectiveness of cyanoacrylate glue and control fractures stinted with contralateral gelatin film. Seven fibrin adhesive-treated and two cyanoacrylate glue-treated guinea pigs were perfused after 60 and 35 days, respectively. The larynges were serial sectioned, and the wound sites were compared. The fibrinogen adhesive system was easier to dispense than cyanoacrylate glue, did not require a completely dry surface, and stabilized within 3 minutes. Cartilage segment alignment with focal, complete fracture healing and symmetrical chondrocyte proliferation were seen in fibrogen adhesive-stinted larynges. In the cyanoacrylate glue-treated larynges, there was no alignment and minimal, asymmetrical chondrocyte proliferation. Gelatin film-stinted controls exhibited similar features. Thus, fibrogen adhesive was easier to apply and more effectively bound laryngeal fractures than cyanoacrylate glue or gelatin film.

  15. Kidney Injury Molecule-1 and Cardiovascular Diseases: From Basic Science to Clinical Practice

    PubMed Central

    Medić, Branislava; Rovčanin, Branislav; Basta Jovanović, Gordana; Radojević-Škodrić, Sanja; Prostran, Milica

    2015-01-01

    Despite the recent findings concerning pathogenesis and novel therapeutic strategies, cardiovascular disease (CVD) still stays the leading cause of morbidity and mortality in patients with renal dysfunction, especially acute kidney injury (AKI). Early detection of patients with impaired renal function with cardiovascular risk may help ensure more aggressive treatment and improve clinical outcome. Kidney injury molecule-1 (KIM-1) is a new, promising marker of kidney damage which is currently the focus of countless studies worldwide. Some recent animal and human studies established KIM-1 as an important marker of acute tubular necrosis (ATN) and reliable predictor of development and prognosis of AKI. Food and Drug Administration (FDA) in USA acclaimed KIM-1 as an AKI biomarker for preclinical drug development. Recent data suggest the importance of monitoring of KIM-1 for early diagnosis and clinical course not only in patients with various forms of AKI and other renal diseases but also in patients with cardiorenal syndrome, heart failure, cardiopulmonary bypass, cardiothoracic surgical interventions in the pediatric emergency setting, and so forth. The aim of this review article is to summarize the literature data concerning KIM-1 as a potential novel marker in the early diagnosis and prediction of clinical outcome of certain cardiovascular diseases. PMID:26697493

  16. Kidney injury molecule-1 expression is closely associated with renal allograft damage.

    PubMed

    Song, Lianlian; Xue, Lijuan; Yu, Jinyu; Zhao, Jun; Zhang, Wenlan; Fu, Yaowen

    2013-08-01

    The aim of our study was to investigate the expression of kidney injury molecule-1 (KIM-1) in renal allograft biopsy samples and assess the clinical significance of its use as a biomarker for tissue damage. A total of 69 renal allograft biopsy samples from 17 patients with normal serum creatinine and 52 cases of increased serum creatinine were collected. They were divided into different groups according to the Banff 2007 diagnostic criteria. KIM-1 expression was detected by immunohistochemical methods and the association of KIM-1 and blood biochemical indexes was analyzed. KIM-1 expression increased as Banff 2007 classification grade increased and was positively correlated with tubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1 expression was strongly positive in the chronic active antibody-mediated rejection group. Interestingly, KIM-1 was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group, 27.3% (3/11) of the cases with normal serum creatinine level showed weakly positive KIM-1 expression in their renal tissues. KIM-1 expression level is positively correlated with renal allograft damage and tubular cell injury. KIM-1 is expressed in tubular epithelial cells before blood biochemical indexes become elevated and morphological changes occur. KIM-1 expression is an early, sensitive, and specific biomarker to determine renal tubular epithelial cell injury in renal allograft tissue.

  17. Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells.

    PubMed

    Wirrig, Christiane; McKean, Jenny S; Wilson, Heather M; Nixon, Graeme F

    2016-09-01

    Inflammation in de-endothelialised arteries contributes to the development of cardiovascular diseases. The process that initiates this inflammatory response is the adhesion of monocytes/macrophages to exposed vascular smooth muscle cells, typically stimulated by cytokines such as tumour necrosis factor-α (TNF). The aim of this study was to determine the effect of the sphingolipid sphingosylphosphorylcholine (SPC) on the interaction of monocytes/macrophages with vascular smooth muscle cells. Rat aortic smooth muscle cells and rat bone marrow-derived macrophages were co-cultured using an in vitro assay following incubation with sphingolipids to assess inter-cellular adhesion. We reveal that SPC inhibits the TNF-induced adhesion of macrophages to smooth muscle cells. This anti-adhesive effect was the result of SPC-induced changes to the smooth muscle cells (but not the macrophages) and was mediated, at least partly, via the sphingosine 1-phosphate receptor subtype 2. Lipid raft domains were also required. Although SPC did not alter expression or membrane distribution of the adhesion proteins intercellular adhesion molecule-1 and vascular cellular adhesion protein-1 in smooth muscle cells, SPC preincubation inhibited the TNF-induced increase in inducible nitric oxide synthase (NOS2) resulting in a subsequent decrease in nitric oxide production. Inhibiting NOS2 activation in smooth muscle cells led to a decrease in the adhesion of macrophages to smooth muscle cells. This study has therefore delineated a novel pathway which can inhibit the interaction between macrophages and vascular smooth muscle cells via SPC-induced repression of NOS2 expression. This mechanism could represent a potential drug target in vascular disease.

  18. Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells.

    PubMed

    Wirrig, Christiane; McKean, Jenny S; Wilson, Heather M; Nixon, Graeme F

    2016-09-01

    Inflammation in de-endothelialised arteries contributes to the development of cardiovascular diseases. The process that initiates this inflammatory response is the adhesion of monocytes/macrophages to exposed vascular smooth muscle cells, typically stimulated by cytokines such as tumour necrosis factor-α (TNF). The aim of this study was to determine the effect of the sphingolipid sphingosylphosphorylcholine (SPC) on the interaction of monocytes/macrophages with vascular smooth muscle cells. Rat aortic smooth muscle cells and rat bone marrow-derived macrophages were co-cultured using an in vitro assay following incubation with sphingolipids to assess inter-cellular adhesion. We reveal that SPC inhibits the TNF-induced adhesion of macrophages to smooth muscle cells. This anti-adhesive effect was the result of SPC-induced changes to the smooth muscle cells (but not the macrophages) and was mediated, at least partly, via the sphingosine 1-phosphate receptor subtype 2. Lipid raft domains were also required. Although SPC did not alter expression or membrane distribution of the adhesion proteins intercellular adhesion molecule-1 and vascular cellular adhesion protein-1 in smooth muscle cells, SPC preincubation inhibited the TNF-induced increase in inducible nitric oxide synthase (NOS2) resulting in a subsequent decrease in nitric oxide production. Inhibiting NOS2 activation in smooth muscle cells led to a decrease in the adhesion of macrophages to smooth muscle cells. This study has therefore delineated a novel pathway which can inhibit the interaction between macrophages and vascular smooth muscle cells via SPC-induced repression of NOS2 expression. This mechanism could represent a potential drug target in vascular disease. PMID:27402344

  19. Evaluation of soluble cell adhesion molecules in atopic dermatitis.

    PubMed

    Koide, M; Furukawa, F; Tokura, Y; Shirahama, S; Takigawa, M

    1997-02-01

    Recent studies have indicated the importance of cell adhesion molecules (CAMs) between the vascular endothelium and activated leukocytes in various inflammatory skin diseases. Soluble forms of CAMs (sCAMs) have also been detected in sera from such diseases. In order to elucidate the role of the soluble forms in skin inflammation, we determined the serum levels of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with atopic dermatitis (AD). Using an enzyme-linked immunosorbent assay, we quantified sCAMs levels in 21 patients with atopic dermatitis and in 16 healthy controls. In severe AD patients, levels of these three types of sCAMs were markedly elevated. sE-selectin was significantly elevated in severe AD over the levels in mild AD. A positive correlation with individual clinical activity was found for changes in the sE-selectin and sVCAM-1 levels. sE-selectin levels were correlated with the serum IgE levels and the number of eosinophils. The sVCAM-1 level was also significantly correlated with the number of monocytes. Among these three molecules, sE-selectin appeared to be the most sensitive clinical parameter in monitoring the clinical course of AD patients.

  20. Cytotoxicity of denture adhesives.

    PubMed

    de Gomes, Pedro Sousa; Figueiral, Maria Helena; Fernandes, Maria Helena R; Scully, Crispian

    2011-12-01

    Ten commercially available denture adhesives, nine soluble formulations (six creams, three powders) and one insoluble product (pad), were analyzed regarding the cytotoxicity profile in direct and indirect assays using L929 fibroblast cells. In the direct assay, fibroblasts were seeded over the surface of a thick adhesive gel (5%, creams; 2.5%, powders and pad). In the indirect assay, cells were cultured in the presence of adhesive extracts prepared in static and dynamic conditions (0.5-2%, creams; 0.25-1%, powders and pad). Cell toxicity was assessed for cell viability/proliferation (MTT assay) and cell morphology (observation of the F-actin cytoskeleton organization by confocal laser scanning microscopy). Direct contact of the L929 fibroblasts with the thick adhesive gels caused no, or only a slight, decrease in cell viability/proliferation. The adhesive extracts (especially those prepared in dynamic conditions) caused significantly higher growth inhibition of fibroblasts and, in addition, caused dose- and time-dependent effects, throughout the 6-72 h exposure time. Also, dose-dependent effects on cell morphology, with evident disruption of the F-actin cytoskeleton organization, were seen in the presence of most adhesives. In conclusion, the adhesives possessed different degrees of cytotoxicity, but similar dose- and time-dependent biological profiles.

  1. [Endothelial cell adhesion molecules].

    PubMed

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

    2014-01-01

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

  2. Focal adhesions in osteoneogenesis

    PubMed Central

    Biggs, M.J.P; Dalby, M.J

    2010-01-01

    As materials technology and the field of tissue engineering advances, the role of cellular adhesive mechanisms, in particular the interactions with implantable devices, becomes more relevant in both research and clinical practice. A key tenet of medical device technology is to use the exquisite ability of biological systems to respond to the material surface or chemical stimuli in order to help develop next-generation biomaterials. The focus of this review is on recent studies and developments concerning focal adhesion formation in osteoneogenesis, with an emphasis on the influence of synthetic constructs on integrin mediated cellular adhesion and function. PMID:21287830

  3. Cell adhesion force microscopy

    PubMed Central

    Sagvolden, G.; Giaever, I.; Pettersen, E. O.; Feder, J.

    1999-01-01

    The adhesion forces of cervical carcinoma cells in tissue culture were measured by using the manipulation force microscope, a novel atomic force microscope. The forces were studied as a function of time and temperature for cells cultured on hydrophilic and hydrophobic polystyrene substrates with preadsorbed proteins. The cells attached faster and stronger at 37°C than at 23°C and better on hydrophilic than on hydrophobic substrates, even though proteins adsorb much better to the hydrophobic substrates. Because cell adhesion serves to control several stages in the cell cycle, we anticipate that the manipulation force microscope can help clarify some cell-adhesion related issues. PMID:9892657

  4. Adhesive Contact Sweeper

    NASA Technical Reports Server (NTRS)

    Patterson, Jonathan D.

    1993-01-01

    Adhesive contact sweeper removes hair and particles vacuum cleaner leaves behind, without stirring up dust. Also cleans loose rugs. Sweeper holds commercially available spools of inverted adhesive tape. Suitable for use in environments in which air kept free of dust; optics laboratories, computer rooms, and areas inhabited by people allergic to dust. For carpets, best used in tandem with vacuum cleaner; first pass with vacuum cleaner removes coarse particles, and second pass with sweeper extracts fine particles. This practice extends useful life of adhesive spools.

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

    PubMed

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

    2010-09-01

    Viral meningitis is characterized by cerebrospinal fluid (CSF) lymphocyte pleocytosis, although neutrophils may predominate in the early phase. The T helper 1 (Th1)/Th2 cytokine balance and expression of adhesion molecules seem to be involved in the CSF chemotaxis. We aimed to determine expression of cytokines and adhesion molecules in enteroviral meningitis. We investigated the serum and CSF levels of adhesion molecules (E-selectin, L-selectin, vascular cell adhesion molecule-1 [VCAM-1], and intracellular adhesion molecule-1 [ICAM-1]) and cytokines (interleukin-12 [IL-12] and IL-4) in 105 children during an outbreak of enteroviral meningitis. Diagnosis was confirmed with positive polymerase chain reaction (PCR) and/or serology for echovirus or Coxsackie virus, and matched with control subjects for clinical features but with negative PCR and/or serology. Apart from VCAM-1, the CSF levels of all investigated inflammatory molecules were significantly increased. In serum, sL-selectin and ICAM-1 levels were significantly higher than control subjects. Serum and CSF L-selectin, serum VCAM-1, and CSF IL-12 were all observed to be expressed in significantly higher levels in the neutrophil-dominant subgroup (72% had duration of symptoms <24 h) than in the lymphocyte-dominant group (87.5% had duration of symptoms >24 h). Serum and CSF ICAM-1 was found at significantly higher levels in the latter group. Evolving expression of adhesion molecules and cytokines indicates a shift from Th1 to Th2 immune responses as infection progresses.

  6. BLOOD LEUKOCYTE EXPRESSION OF LFA-1 AND INTRACELLULAR ADHESION MOLECULE-1 (ICAM-1) AFTER INHALATION OF ULTRAFINE CARBON PARTICLES. (R827354C003)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  7. P2Y2 Receptor-mediated Lymphotoxin-α Secretion Regulates Intercellular Cell Adhesion Molecule-1 Expression in Vascular Smooth Muscle Cells*

    PubMed Central

    Seye, Cheikh I.; Agca, Yuksel; Agca, Cansu; Derbigny, Wilbert

    2012-01-01

    The proinflammatory cytokine lymphotoxin-α (LTA) is thought to contribute to the pathogenesis of atherosclerosis. However, the mechanisms that regulate its expression in vascular smooth muscle cells (VSMC) are poorly understood. The ability of exogenous nucleotides to stimulate LTA production was evaluated in VSMC by ELISA. The P2Y2 nucleotide receptor (P2Y2R) agonist UTP stimulates a strong and sustained release of LTA from WT but not P2Y2R−/− SMC. Assessment of LTA gene transcription by LTA promoter-luciferase construct indicated that LTA levels are controlled at the level of transcription. We show using RNAi techniques that knockdown of the actin-binding protein filamin-A (FLNa) severely impaired nucleotide-induced Rho activation and consequent Rho-mediated LTA secretion. Reintroduction of FLNa in FLNa RNAi SMC rescued UTP-induced LTA expression. In addition, we found that UTP-stimulated LTA secretion is not sensitive to brefeldin A, which blocks the formation of vesicles involved in protein transport from the endoplasmic reticulum to the Golgi apparatus, suggesting that P2Y2R/filamin-mediated secretion of LTA is independent of the endoplasmic reticulum/Golgi secretory vesicle route. Furthermore, UTP selectively induces ICAM-1 expression in WT but not SMC expressing a truncated P2Y2R deficient in LTA secretion. These data suggest that P2Y2R recruits FLNa to provide a cytoskeletal scaffold necessary for Rho signaling pathway upstream of LTA release and subsequent stimulation of ICAM-1 expression on vascular smooth muscle cells. PMID:22298782

  8. CKIP-1 ameliorates high glucose-induced expression of fibronectin and intercellular cell adhesion molecule-1 by activating the Nrf2/ARE pathway in glomerular mesangial cells.

    PubMed

    Gong, Wenyan; Chen, Cheng; Xiong, Fengxiao; Yang, Zhiying; Wang, Yu; Huang, Junying; Liu, Peiqing; Huang, Heqing

    2016-09-15

    Glucose and lipid metabolism disorders as well as oxidative stress (OSS) play important roles in diabetic nephropathy (DN). Glucose and lipid metabolic dysfunctions are the basic pathological changes of chronic microvascular complications of diabetes mellitus, such as DN. OSS can lead to the accumulation of extracellular matrix and inflammatory factors which will accelerate the progress of DN. Casein kinase 2 interacting protein-1 (CKIP-1) mediates adipogenesis, cell proliferation and inflammation under many circumstances. However, whether CKIP-1 is involved in the development of DN remains unknown. Here, we show that CKIP-1 is a novel regulator of resisting the development of DN and the underlying molecular mechanism is related to activating the nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) antioxidative stress pathway. The following findings were obtained: (1) The treatment of glomerular mesangial cells (GMCs) with high glucose (HG) decreased CKIP-1 levels in a time-dependent manner; (2) CKIP-1 overexpression dramatically reduced fibronectin (FN) and intercellular adhesionmolecule-1 (ICAM-1) expression. Depletion of CKIP-1 further induced the production of FN and ICAM-1; (3) CKIP-1 promoted the nuclear accumulation, DNA binding, and transcriptional activity of Nrf2. Moreover, CKIP-1 upregulated the expression of Nrf2 downstream genes, heme oxygenase (HO-1) and superoxide dismutase 1 (SOD1); and ultimately decreased the levels of reactive oxygen species (ROS). The molecular mechanisms clarify that the advantageous effect of CKIP-1 on DN are well connected with the activation of the Nrf2/ARE antioxidative stress pathway. PMID:27481061

  9. Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM-1) in bladder cancer patients after bacillus Calmette-Guérin (BCG) immunotherapy.

    PubMed Central

    Jackson, A M; Alexandroff, A B; Kelly, R W; Skibinska, A; Esuvaranathan, K; Prescott, S; Chisholm, G D; James, K

    1995-01-01

    Intravesical immunotherapy for carcinoma in situ of the bladder is arguably the most effective form of tumour immunotherapy described to date. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients' urine. This study concerns the production of IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and soluble ICAM-1 (sICAM-1) throughout the six weekly instillations which comprise a therapeutic course. Sequential instillations of BCG induced secretion of IL-1 beta, IL-2, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and sICAM-1 into urine. The responses were heterogeneous between patients and cytokines, but some general trends were evident. Although cytokine levels were initially low, their concentration increased with repeated instillation of BCG. Certain cytokines (e.g. IL-6, IL-8 and IL-10) could be detected after the first instillation, whilst others (e.g. IL-2 and IFN-gamma) were not detected until after the third or fourth instillation. Interestingly, IL-4 was not detected, perhaps suggesting a differential effect on Th2-like responses. Some patients produced particularly elevated or non-detectable levels of cytokines, and a positive correlation was found between the production of various cytokines. The production of a particular cytokine did not correspond with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value will be determined in a larger series of patients. However, as these potent immunomodulators are thought to be important for the 75% complete clinical response observed with BCG therapy, there remains the possibility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary forerunner to full prognostic evaluation of such immunological data. PMID:7882559

  10. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

    PubMed

    Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

    2016-10-01

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. PMID:27431456

  11. Anti-interleukin-33 Reduces Ovalbumin-Induced Nephrotoxicity and Expression of Kidney Injury Molecule-1

    PubMed Central

    2016-01-01

    Purpose: To evaluate the effect of anti-interleukin-33 (anti-IL-33) on a mouse model of ovalbumin (OVA)-induced acute kidney injury (AKI). Methods: Twenty-four female BALB/c mice were assigned to 4 groups: group A (control, n=6) was administered sterile saline intraperitoneally (i.p.) and intranasally (i.n.); group B (allergic, n=6) was administered i.p./i.n. OVA challenge; group C (null treatment, n=6) was administered control IgG i.p. before OVA challenge; and group D (anti-IL-33, n=6) was pretreated with 3.6 µg of anti-IL-33 i.p. before every OVA challenge. The following were evaluated after sacrifice: serum blood urea nitrogen and creatinine levels, Kidney injury molecule-1 gene (Kim-1) and protein (KIM-1) expression in renal parenchyma, and expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phosphorylated endothelial NOS (p-eNOS), and phosphorylated AMP kinase (p-AMPK) proteins in renal parenchyma. Results: After OVA injection and intranasal challenge, mice in groups B and C showed significant increases in the expression of Kim-1 at both the mRNA and protein levels. After anti-IL-33 treatment, mice in group D showed significant Kim-1 down-regulation at the mRNA and protein levels. Group D also showed significantly lower COX-2 protein expression, marginally lesser iNOS expression than groups B and C, and p-eNOS and p-AMPK expression at baseline levels. Conclusions: Kim-1 could be a useful marker for detecting early-stage renal injury in mouse models of OVA-induced AKI. Further, anti-IL-33 might have beneficial effects on these mouse models. PMID:27377943

  12. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

    PubMed

    Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

    2016-10-01

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents.

  13. Adhesion and migration of avian neural crest cells on fibronectin require the cooperating activities of multiple integrins of the (beta)1 and (beta)3 families.

    PubMed

    Testaz, S; Delannet, M; Duband, J

    1999-12-01

    combination using antibodies or recombinant VCAM-1 and PECAM-1 molecules as a substratum, was required for migration but was not sufficient to produce migration of the cell population as efficiently as with fibronectin. In conclusion, our study indicates that neural crest cells express a multiplicity of fibronectin-binding integrins and suggests that dispersion of the cell population requires cooperation between distinct integrins regulating different events of cell adhesion, locomotion and, possibly, proliferation and survival. PMID:10574719

  14. Optical adhesive property study

    SciTech Connect

    Sundvold, P.D.

    1996-01-01

    Tests were performed to characterize the mechanical and thermal properties of selected optical adhesives to identify the most likely candidate which could survive the operating environment of the Direct Optical Initiation (DOI) program. The DOI system consists of a high power laser and an optical module used to split the beam into a number of channels to initiate the system. The DOI requirements are for a high shock environment which current military optical systems do not operate. Five candidate adhesives were selected and evaluated using standardized test methods to determine the adhesives` physical properties. EC2216, manufactured by 3M, was selected as the baseline candidate adhesive based on the test results of the physical properties.

  15. Adhesion of Lunar Dust

    NASA Technical Reports Server (NTRS)

    Walton, Otis R.

    2007-01-01

    This paper reviews the physical characteristics of lunar dust and the effects of various fundamental forces acting on dust particles on surfaces in a lunar environment. There are transport forces and adhesion forces after contact. Mechanical forces (i.e., from rover wheels, astronaut boots and rocket engine blast) and static electric effects (from UV photo-ionization and/or tribo-electric charging) are likely to be the major contributors to the transport of dust particles. If fine regolith particles are deposited on a surface, then surface energy-related (e.g., van der Walls) adhesion forces and static-electric-image forces are likely to be the strongest contributors to adhesion. Some measurement techniques are offered to quantify the strength of adhesion forces. And finally some dust removal techniques are discussed.

  16. Adhesives for Aerospace

    NASA Technical Reports Server (NTRS)

    Meade, L. E.

    1985-01-01

    The industry is hereby challenged to integrate adhesive technology with the total structure requirements in light of today's drive into automation/mechanization. The state of the art of adhesive technology is fairly well meeting the needs of the structural designers, the processing engineer, and the inspector, each on an individual basis. The total integration of these needs into the factory of the future is the next collective hurdle to be achieved. Improved processing parameters to fit the needs of automation/mechanization will necessitate some changes in the adhesive forms, formulations, and chemistries. Adhesives have, for the most part, kept up with the needs of the aerospace industry, normally leading the rest of the industry in developments. The wants of the aerospace industry still present a challenge to encompass all elements, achieving a totally integrated joined and sealed structural system. Better toughness with hot-wet strength improvements is desired. Lower cure temperatures, longer out times, and improved corrosion inhibition are desired.

  17. Dry adhesives with sensing features

    NASA Astrophysics Data System (ADS)

    Krahn, J.; Menon, C.

    2013-08-01

    Geckos are capable of detecting detachment of their feet. Inspired by this basic observation, a novel functional dry adhesive is proposed, which can be used to measure the instantaneous forces and torques acting on an adhesive pad. Such a novel sensing dry adhesive could potentially be used by climbing robots to quickly realize and respond appropriately to catastrophic detachment conditions. The proposed torque and force sensing dry adhesive was fabricated by mixing Carbon Black (CB) and Polydimethylsiloxane (PDMS) to form a functionalized adhesive with mushroom caps. The addition of CB to PDMS resulted in conductive PDMS which, when under compression, tension or torque, resulted in a change in the resistance across the adhesive patch terminals. The proposed design of the functionalized dry adhesive enables distinguishing an applied torque from a compressive force in a single adhesive pad. A model based on beam theory was used to predict the change in resistance across the terminals as either a torque or compressive force was applied to the adhesive patch. Under a compressive force, the sensing dry adhesive was capable of measuring compression stresses from 0.11 Pa to 20.9 kPa. The torque measured by the adhesive patch ranged from 2.6 to 10 mN m, at which point the dry adhesives became detached. The adhesive strength was 1.75 kPa under an applied preload of 1.65 kPa for an adhesive patch with an adhesive contact area of 7.07 cm2.

  18. A role for cell adhesion in beryllium-mediated lung disease

    SciTech Connect

    Hong-geller, Elizabeth

    2008-01-01

    Chronic beryllium disease (CBD) is a debilitating lung disorder in which exposure to the lightweight metal beryllium (Be) causes the accumulation of beryllium-specific CD4+ T cells in the lung and formation of noncaseating pulmonary granulomas. Treatment for CBD patients who exhibit progressive pulmonary decline is limited to systemic corticosteroids, which suppress the severe host inflammatory response. Studies in the past several years have begun to highlight cell-cell adhesion interactions in the development of Be hypersensitivity and CBD. In particular, the high binding affinity between intercellular adhesion molecule 1 (I-CAM1) on lung epithelial cells and the {beta}{sub 2} integrin LFA-1 on migrating lymphocytes and macrophages regulates the concerted rolling of immune cells to sites of inflammation in the lung. In this review, we discuss the evidence that implicates cell adhesion processes in onset of Be disease and the potential of cell adhesion as an intervention point for development of novel therapies.

  19. Magnetic field switchable dry adhesives.

    PubMed

    Krahn, Jeffrey; Bovero, Enrico; Menon, Carlo

    2015-02-01

    A magnetic field controllable dry adhesive device is manufactured. The normal adhesion force can be increased or decreased depending on the presence of an applied magnetic field. If the magnetic field is present during the entire normal adhesion test cycle which includes both applying a preloading force and measuring the pulloff pressure, a decrease in adhesion is observed when compared to when there is no applied magnetic field. Similarly, if the magnetic field is present only during the preload portion of the normal adhesion test cycle, a decrease in adhesion is observed because of an increased stiffness of the magnetically controlled dry adhesive device. When the applied magnetic field is present during only the pulloff portion of the normal adhesion test cycle, either an increase or a decrease in normal adhesion is observed depending on the direction of the applied magnetic field.

  20. Regulation of Cell Adhesion Strength by Peripheral Focal Adhesion Distribution

    PubMed Central

    Elineni, Kranthi Kumar; Gallant, Nathan D.

    2011-01-01

    Cell adhesion to extracellular matrices is a tightly regulated process that involves the complex interplay between biochemical and mechanical events at the cell-adhesive interface. Previous work established the spatiotemporal contributions of adhesive components to adhesion strength and identified a nonlinear dependence on cell spreading. This study was designed to investigate the regulation of cell-adhesion strength by the size and position of focal adhesions (FA). The cell-adhesive interface was engineered to direct FA assembly to the periphery of the cell-spreading area to delineate the cell-adhesive area from the cell-spreading area. It was observed that redistributing the same adhesive area over a larger cell-spreading area significantly enhanced cell-adhesion strength, but only up to a threshold area. Moreover, the size of the peripheral FAs, which was interpreted as an adhesive patch, did not directly govern the adhesion strength. Interestingly, this is in contrast to the previously reported functional role of FAs in regulating cellular traction where sizes of the peripheral FAs play a critical role. These findings demonstrate, to our knowledge for the first time, that two spatial regimes in cell-spreading area exist that uniquely govern the structure-function role of FAs in regulating cell-adhesion strength. PMID:22208188

  1. Adhesive particle shielding

    DOEpatents

    Klebanoff, Leonard Elliott; Rader, Daniel John; Walton, Christopher; Folta, James

    2009-01-06

    An efficient device for capturing fast moving particles has an adhesive particle shield that includes (i) a mounting panel and (ii) a film that is attached to the mounting panel wherein the outer surface of the film has an adhesive coating disposed thereon to capture particles contacting the outer surface. The shield can be employed to maintain a substantially particle free environment such as in photolithographic systems having critical surfaces, such as wafers, masks, and optics and in the tools used to make these components, that are sensitive to particle contamination. The shield can be portable to be positioned in hard-to-reach areas of a photolithography machine. The adhesive particle shield can incorporate cooling means to attract particles via the thermophoresis effect.

  2. Natural Underwater Adhesives

    PubMed Central

    Stewart, Russell J.; Ransom, Todd C.; Hlady, Vladimir

    2011-01-01

    The general topic of this review is protein-based underwater adhesives produced by aquatic organisms. The focus is on mechanisms of interfacial adhesion to native surfaces and controlled underwater solidification of natural water-borne adhesives. Four genera that exemplify the broad range of function, general mechanistic features, and unique adaptations are discussed in detail: blue mussels, acorn barnacles, sandcastle worms, and freshwater caddisfly larva. Aquatic surfaces in nature are charged and in equilibrium with their environment, populated by an electrical double layer of ions as well as adsorbed natural polyelectrolytes and microbial biofilms. Surface adsorption of underwater bioadhesives likely occurs by exchange of surface bound ligands by amino acid sidechains, driven primarily by relative affinities and effective concentrations of polymeric functional groups. Most aquatic organisms exploit modified amino acid sidechains, in particular phosphorylated serines and hydroxylated tyrosines (dopa), with high-surface affinity that form coordinative surface complexes. After delivery to the surfaces as a fluid, permanent natural adhesives solidify to bear sustained loads. Mussel plaques are assembled in a manner superficially reminiscent of in vitro layer-by-layer strategies, with sequentially delivered layers associated through Fe(dopa)3 coordination bonds. The adhesives of sandcastle worms, caddisfly larva, and barnacles may be delivered in a form somewhat similar to in vitro complex coacervation. Marine adhesives are secreted, or excreted, into seawater that has a significantly higher pH and ionic strength than the internal environment. Empirical evidence suggests these environment triggers could provide minimalistic, fail-safe timing mechanisms to prevent premature solidification (insolubilization) of the glue within the secretory system, yet allow rapid solidification after secretion. Underwater bioadhesives are further strengthened by secondary covalent

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

    PubMed Central

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

    2001-01-01

    The expression of adhesion molecules in synovium in patients with Lyme arthritis is surely critical in the control of Borrelia burgdorferi infection but may also have pathologic consequences. For example, molecular mimicry between a dominant T-cell epitope of B. burgdorferi outer surface protein A and an adhesion molecule, human lymphocyte function-associated antigen 1 (LFA-1), has been implicated in the pathogenesis of treatment-resistant Lyme arthritis. Using immunohistochemical methods, we examined synovial samples for expression of adhesion molecules in 29 patients with treatment-resistant Lyme arthritis and in 15 patients with rheumatoid arthritis or chronic inflammatory monoarthritis. In Lyme arthritis synovia, endothelial cells showed intense expression of P-selectin and vascular adhesion protein-1 (VAP-1). Expression of LFA-1 was also intense on infiltrating cells, particularly in lymphoid aggregates, and intercellular adhesion molecule-1 (ICAM-1) was markedly expressed on synovial lining and endothelial and infiltrating cells. Moderate expression of vascular cell adhesion molecule-1 (VCAM-1) was seen on synovial lining and endothelial cells, and mild expression of its ligand, very late antigen-4, was apparent in perivascular lymphoid infiltrates. Except for lesser expression of VCAM-1 in Lyme synovia, the levels of expression of these adhesion molecules were similar in the three patient groups. We conclude that certain adhesion molecules, including ICAM-1 and LFA-1, are expressed intensely in the synovia of patients with Lyme arthritis. Upregulation of LFA-1 on lymphocytes in this lesion may be critical in the pathogenesis of treatment-resistant Lyme arthritis. PMID:11179355

  4. Elastomer toughened polyimide adhesives

    NASA Technical Reports Server (NTRS)

    St.clair, A. K.; St.clair, T. L. (Inventor)

    1983-01-01

    A rubber-toughened addition-type polyimide composition is disclosed which has excellent high temperature bonding characteristics in the fully cured state, and improved peel strength and adhesive fracture resistance physical property characteristics. The process for making the improved adhesive involves preparing the rubber containing amic acid prepolymer by chemically reacting an amine-terminated elastomer and an aromatic diamine with an aromatic dianhydride with which a reactive chain stopper anhydride was mixed, and utilizing solvent or mixture of solvents for the reaction.

  5. Adhesion in hydrogel contacts

    NASA Astrophysics Data System (ADS)

    Torres, J. R.; Jay, G. D.; Kim, K.-S.; Bothun, G. D.

    2016-05-01

    A generalized thermomechanical model for adhesion was developed to elucidate the mechanisms of dissipation within the viscoelastic bulk of a hyperelastic hydrogel. Results show that in addition to the expected energy release rate of interface formation, as well as the viscous flow dissipation, the bulk composition exhibits dissipation due to phase inhomogeneity morphological changes. The mixing thermodynamics of the matrix and solvent determines the dynamics of the phase inhomogeneities, which can enhance or disrupt adhesion. The model also accounts for the time-dependent behaviour. A parameter is proposed to discern the dominant dissipation mechanism in hydrogel contact detachment.

  6. Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis.

    PubMed

    Chen, Yih-Fung; Chiu, Wen-Tai; Chen, Ying-Ting; Lin, Pey-Yun; Huang, Huey-Jy; Chou, Cheng-Yang; Chang, Hsien-Chang; Tang, Ming-Jer; Shen, Meng-Ru

    2011-09-13

    Store-operated Ca(2+) entry (SOCE) is the principal Ca(2+) entry mechanism in nonexcitable cells. Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca(2+) sensor that triggers SOCE activation. However, the role of STIM1 in regulating cancer progression remains controversial and its clinical relevance is unclear. Here we show that STIM1-dependent signaling is important for cervical cancer cell proliferation, migration, and angiogenesis. STIM1 overexpression in tumor tissue is noted in 71% cases of early-stage cervical cancer. In tumor tissues, the level of STIM1 expression is significantly associated with the risk of metastasis and survival. EGF-stimulated cancer cell migration requires STIM1 expression and EGF increases the interaction between STIM1 and Orai1 in juxta-membrane areas, and thus induces Ca(2+) influx. STIM1 involves the activation of Ca(2+)-regulated protease calpain, as well as Ca(2+)-regulated cytoplasmic kinase Pyk2, which regulate the focal-adhesion dynamics of migratory cervical cancer cells. Because of an increase of p21 protein levels and a decrease of Cdc25C protein levels, STIM1-silencing in cervical cancer cells significantly inhibits cell proliferation by arresting the cell cycle at the S and G2/M phases. STIM1 also regulates the production of VEGF in cervical cancer cells. Interference with STIM1 expression or blockade of SOCE activity inhibits tumor angiogenesis and growth in animal models, confirming the crucial role of STIM1-mediated Ca(2+) influx in aggravating tumor development in vivo. These results make STIM1-dependent signaling an attractive target for therapeutic intervention. PMID:21876174

  7. Switchable bio-inspired adhesives

    NASA Astrophysics Data System (ADS)

    Kroner, Elmar

    2015-03-01

    Geckos have astonishing climbing abilities. They can adhere to almost any surface and can run on walls and even stick to ceilings. The extraordinary adhesion performance is caused by a combination of a complex surface pattern on their toes and the biomechanics of its movement. These biological dry adhesives have been intensely investigated during recent years because of the unique combination of adhesive properties. They provide high adhesion, allow for easy detachment, can be removed residue-free, and have self-cleaning properties. Many aspects have been successfully mimicked, leading to artificial, bio-inspired, patterned dry adhesives, and were addressed and in some aspects they even outperform the adhesion capabilities of geckos. However, designing artificial patterned adhesion systems with switchable adhesion remains a big challenge; the gecko's adhesion system is based on a complex hierarchical surface structure and on advanced biomechanics, which are both difficult to mimic. In this paper, two approaches are presented to achieve switchable adhesion. The first approach is based on a patterned polydimethylsiloxane (PDMS) polymer, where adhesion can be switched on and off by applying a low and a high compressive preload. The switch in adhesion is caused by a reversible mechanical instability of the adhesive silicone structures. The second approach is based on a composite material consisting of a Nickel- Titanium (NiTi) shape memory alloy and a patterned adhesive PDMS layer. The NiTi alloy is trained to change its surface topography as a function of temperature, which results in a change of the contact area and of alignment of the adhesive pattern towards a substrate, leading to switchable adhesion. These examples show that the unique properties of bio-inspired adhesives can be greatly improved by new concepts such as mechanical instability or by the use of active materials which react to external stimuli.

  8. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives.

    PubMed

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-11-01

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm(2) provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects.

  9. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives

    PubMed Central

    2015-01-01

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm2 provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects. PMID:26457864

  10. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives.

    PubMed

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-11-01

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm(2) provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects. PMID:26457864

  11. Wood Composite Adhesives

    NASA Astrophysics Data System (ADS)

    Gomez-Bueso, Jose; Haupt, Robert

    The global environment, in which phenolic resins are being used for wood composite manufacture, has changed significantly during the last decade. This chapter reviews trends that are driving the use and consumption of phenolic resins around the world. The review begins with recent data on volume usage and regional trends, followed by an analysis of factors affecting global markets. In a section on environmental factors, the impact of recent formaldehyde emission regulations is discussed. The section on economics introduces wood composite production as it relates to the available adhesive systems, with special emphasis on the technical requirement to improve phenolic reactivity. Advances in composite process technology are introduced, especially in regard to the increased demands the improvements place upon adhesive system performance. The specific requirements for the various wood composite families are considered in the context of adhesive performance needs. The results of research into current chemistries are discussed, with a review of recent findings regarding the mechanisms of phenolic condensation and acceleration. Also, the work regarding alternate natural materials, such as carbohydrates, lignins, tannins, and proteinaceous materials, is presented. Finally, new developments in alternative adhesive technologies are reported.

  12. Rapid adhesive bonding concepts

    NASA Technical Reports Server (NTRS)

    Stein, B. A.; Tyeryar, J. R.; Hodges, W. T.

    1984-01-01

    Adhesive bonding in the aerospace industry typically utilizes autoclaves or presses which have considerable thermal mass. As a consequence, the rates of heatup and cooldown of the bonded parts are limited and the total time and cost of the bonding process is often relatively high. Many of the adhesives themselves do not inherently require long processing times. Bonding could be performed rapidly if the heat was concentrated in the bond lines or at least in the adherends. Rapid adhesive bonding concepts were developed to utilize induction heating techniques to provide heat directly to the bond line and/or adherends without heating the entire structure, supports, and fixtures of a bonding assembly. Bonding times for specimens are cut by a factor of 10 to 100 compared to standard press bonding. The development of rapid adhesive bonding for lap shear specimens (per ASTM D1003 and D3163), for aerospace panel bonding, and for field repair needs of metallic and advanced fiber reinforced polymeric matrix composite structures are reviewed.

  13. Resistance heating releases structural adhesive

    NASA Technical Reports Server (NTRS)

    Glemser, N. N.

    1967-01-01

    Composite adhesive package bonds components together for testing and enables separation when testing is completed. The composite of adhesives, insulation and a heating element separate easily when an electrical current is applied.

  14. 3-D foam adhesive deposition

    NASA Technical Reports Server (NTRS)

    Lemons, C. R.; Salmassy, O. K.

    1976-01-01

    Bonding method, which reduces amount and weight of adhesive, is applicable to foam-filled honeycomb constructions. Novel features of process include temperature-viscosity control and removal of excess adhesive by transfer to cellophane film.

  15. Coating Reduces Ice Adhesion

    NASA Technical Reports Server (NTRS)

    Smith, Trent; Prince, Michael; DwWeese, Charles; Curtis, Leslie

    2008-01-01

    The Shuttle Ice Liberation Coating (SILC) has been developed to reduce the adhesion of ice to surfaces on the space shuttle. SILC, when coated on a surface (foam, metal, epoxy primer, polymer surfaces), will reduce the adhesion of ice by as much as 90 percent as compared to the corresponding uncoated surface. This innovation is a durable coating that can withstand several cycles of ice growth and removal without loss of anti-adhesion properties. SILC is made of a binder composed of varying weight percents of siloxane(s), ethyl alcohol, ethyl sulfate, isopropyl alcohol, and of fine-particle polytetrafluoroethylene (PTFE). The combination of these components produces a coating with significantly improved weathering characteristics over the siloxane system alone. In some cases, the coating will delay ice formation and can reduce the amount of ice formed. SILC is not an ice prevention coating, but the very high water contact angle (greater than 140 ) causes water to readily run off the surface. This coating was designed for use at temperatures near -170 F (-112 C). Ice adhesion tests performed at temperatures from -170 to 20 F (-112 to -7 C) show that SILC is a very effective ice release coating. SILC can be left as applied (opaque) or buffed off until the surface appears clear. Energy dispersive spectroscopy (EDS) and x-ray photoelectron spectroscopy (XPS) data show that the coating is still present after buffing to transparency. This means SILC can be used to prevent ice adhesion even when coating windows or other objects, or items that require transmission of optical light. Car windshields are kept cleaner and SILC effectively mitigates rain and snow under driving conditions.

  16. Adhesion behaviors on superhydrophobic surfaces.

    PubMed

    Zhu, Huan; Guo, Zhiguang; Liu, Weimin

    2014-04-18

    The adhesion behaviors of superhydrophobic surfaces have become an emerging topic to researchers in various fields as a vital step in the interactions between materials and organisms/materials. Controlling the chemical compositions and topological structures via various methods or technologies is essential to fabricate and modulate different adhesion properties, such as low-adhesion, high-adhesion and anisotropic adhesion on superhydrophobic surfaces. We summarize the recent developments in both natural superhydrophobic surfaces and artificial superhydrophobic surfaces with various adhesions and also pay attention to superhydrophobic surfaces switching between low- and high-adhesion. The methods to regulate or translate the adhesion of superhydrophobic surfaces can be considered from two perspectives. One is to control the chemical composition and change the surface geometric structure on the surfaces, respectively or simultaneously. The other is to provide external stimulations to induce transitions, which is the most common method for obtaining switchable adhesions. Additionally, adhesion behaviors on solid-solid interfaces, such as the behaviors of cells, bacteria, biomolecules and icing on superhydrophobic surfaces are also noticeable and controversial. This review is aimed at giving a brief and crucial overview of adhesion behaviors on superhydrophobic surfaces.

  17. Environmentally compliant adhesive joining technology

    SciTech Connect

    Tira, J.S.

    1996-08-01

    Adhesive joining offers one method of assembling products. Advantages of adhesive joining/assembly include distribution of applied forces, lighter weight, appealing appearance, etc. Selecting environmentally safe adhesive materials and accompanying processes is paramount in today`s business climate if a company wants to be environmentally conscious and stay in business. Four areas of adhesive joining (adhesive formulation and selection, surface preparation, adhesive bonding process, waste and pollution generation/cleanup/management) all need to be carefully evaluated before adhesive joining is selected for commercial as well as military products. Designing for six sigma quality must also be addressed in today`s global economy. This requires material suppliers and product manufacturers to work even closer together.

  18. Ceramic microstructure and adhesion

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.

    1985-01-01

    When a ceramic is brought into contact with a ceramic, a polymer, or a metal, strong bond forces can develop between the materials. The bonding forces will depend upon the state of the surfaces, cleanliness and the fundamental properties of the two solids, both surface and bulk. Adhesion between a ceramic and another solid are discussed from a theoretical consideration of the nature of the surfaces and experimentally by relating bond forces to interface resulting from solid state contact. Surface properties of ceramics correlated with adhesion include, orientation, reconstruction and diffusion as well as the chemistry of the surface specie. Where a ceramic is in contact with a metal their interactive chemistry and bond strength is considered. Bulk properties examined include elastic and plastic behavior in the surficial regions, cohesive binding energies, crystal structures and crystallographic orientation. Materials examined with respect to interfacial adhesive interactions include silicon carbide, nickel zinc ferrite, manganese zinc ferrite, and aluminum oxide. The surfaces of the contacting solids are studied both in the atomic or molecularly clean state and in the presence of selected surface contaminants.

  19. Development of phosphorylated adhesives

    NASA Technical Reports Server (NTRS)

    Bilow, N.; Giants, T. W.; Jenkins, R. K.; Campbell, P. L.

    1983-01-01

    The synthesis of epoxy prepolymers containing phosphorus was carried out in such a manner as to provide adhesives containing at least 5 percent of this element. The purpose of this was to impart fire retardant properties to the adhesive. The two epoxy derivatives, bis(4-glycidyl-oxyphenyl)phenylphosphine oxide and bis(4-glycidyl-2-methoxyphenyl)phenylphosphonate, and a curing agent, bis(3-aminophenyl)methylphosphine oxide, were used in conjunction with one another and along with conventional epoxy resins and curing agents to bond Tedlar and Polyphenylethersulfone films to Kerimid-glass syntactic foam-filled honeycomb structures. Elevated temperatures are required to cure the epoxy resins with the phosphorus-contaning diamine; however, when Tedlar is being bonded, lower curing temperatures must be used to avoid shrinkage and the concomitant formation of surface defects. Thus, the phosphorus-containing aromatic amine curing agent cannot be used alone, although it is possible to use it in conjunction with an aliphatic amine which would allow lower cure temperatures to be used. The experimental epoxy resins have not provided adhesive bonds quite as strong as those provided by Epon 828 when compared in peel tests, but the differences are not very significant. It should be noted, if optimum properties are to be realized. In any case the fire retardant characteristics of the neat resin systems obtained are quite pronounced, since in most cases the self-extinguishing properties are evident almost instantly when specimens are removed from a flame.

  20. Ceramic microstructure and adhesion

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.

    1984-01-01

    When a ceramic is brought into contact with a ceramic, a polymer, or a metal, strong bond forces can develop between the materials. The bonding forces will depend upon the state of the surfaces, cleanliness and the fundamental properties of the two solids, both surface and bulk. Adhesion between a ceramic and another solid are discussed from a theoretical consideration of the nature of the surfaces and experimentally by relating bond forces to interface resulting from solid state contact. Surface properties of ceramics correlated with adhesion include, orientation, reconstruction and diffusion as well as the chemistry of the surface specie. Where a ceramic is in contact with a metal their interactive chemistry and bond strength is considered. Bulk properties examined include elastic and plastic behavior in the surficial regions, cohesive binding energies, crystal structures and crystallographic orientation. Materials examined with respect to interfacial adhesive interactions include silicon carbide, nickel zinc ferrite, manganese zinc ferrite, and aluminum oxide. The surfaces of the contacting solids are studied both in the atomic or molecularly clean state and in the presence of selected surface contaminants.

  1. Adhesion barrier reduces postoperative adhesions after cardiac surgery.

    PubMed

    Kaneko, Yukihiro; Hirata, Yasutaka; Achiwa, Ikuya; Morishita, Hiroyuki; Soto, Hajime; Kobayahsi, Jotaro

    2012-06-01

    Reoperation in cardiac surgery is associated with increased risk due to surgical adhesions. Application of a bioresorbable material could theoretically reduce adhesions and allow later development of a free dissection plane for cardiac reoperation. Twenty-one patients in whom a bioresorbable hyaluronic acid-carboxymethylcellulose adhesion barrier had been applied in a preceding surgery underwent reoperations, while 23 patients underwent reoperations during the same period without a prior adhesion barrier. Blinded observers graded the tenacity of the adhesions from surgical video recordings of the reoperations. No excessive bleeding requiring wound reexploration, mediastinal infection, or other complication attributable to the adhesion barrier occurred. Multiple regression analysis showed that shorter duration of the preceding surgery, non-use of cardiopulmonary bypass in the preceding surgery, and use of the adhesion barrier were significantly associated with less tenacious surgical adhesions. The use of a bioresorbable material in cardiac surgery reduced postoperative adhesions, facilitated reoperation, and did not promote complications. The use of adhesion barrier is recommended in planned staged procedures and those in which future reoperation is likely.

  2. Loss of Reelin protects against atherosclerosis by reducing leukocyte-endothelial adhesion and lesion macrophage accumulation

    PubMed Central

    Ding, Yinyuan; Huang, Linzhang; Xian, Xunde; Yuhanna, Ivan S.; Wasser, Catherine R.; Frotscher, Michael; Mineo, Chieko; Shaul, Philip W.; Herz, Joachim

    2016-01-01

    The multimodular glycoprotein Reelin controls neuronal migration and synaptic transmission by binding to Apolipoprotein E receptor-2 (Apoer2) and very low-density lipoprotein receptor (Vldlr) on neurons. In the periphery, Reelin is produced by the liver, circulates in blood and promotes thrombosis and hemostasis. To investigate if Reelin influences atherogenesis we studied atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr−/−) mice in which we inducibly deleted Reelin either ubiquitously or only in the liver, thus preventing the production of circulating Reelin. In both types of Reelin-deficient mice, atherosclerosis progression was markedly attenuated, and macrophage content and endothelial cell staining for vascular cell adhesion molecule-1 (VCAM1) and intercellular adhesion molecule-1 (ICAM1) were reduced at the sites of atherosclerotic lesions. Intravital microscopy revealed decreased leukocyte-endothelial adhesion in the Reelin-deficient mice. In cultured human endothelial cells, Reelin enhanced monocyte adhesion and increased ICAM-1, VCAM-1 and E-selectin expression by suppressing endothelial nitric oxide synthase (eNOS) activity and increasing the activity of NF-kB in an Apoer2-dependent manner. These findings suggest that circulating Reelin promotes atherosclerosis by increasing vascular inflammation, and that reducing or inhibiting circulating Reelin may present a novel approach for the prevention of cardiovascular disease. PMID:26980442

  3. Fetal exposure to a diabetic intrauterine environment resulted in a failure of cord blood endothelial progenitor cell adaptation against chronic hypoxia

    PubMed Central

    Dincer, U Deniz

    2015-01-01

    Gestational diabetes mellitus (GDM) has long-term health consequences, and fetal exposure to a diabetic intrauterine environment increases cardiovascular risk for her adult offspring. Some part of this could be related to their endothelial progenitor cells (EPCs). Understanding the vessel-forming ability of human umbilical cord blood (HUCB)-derived endothelial colony-forming cells (ECFCs) against pathological stress such as GDM response to hypoxia could generate new therapeutic strategies. This study aims to investigate the role of chronic hypoxia in EPCs functional and vessel-forming ability in GDM subjects. Each ECFC was expressed in endothelial and pro-angiogenic specific markers, namely endothelial nitric oxide synthase (eNOS), platelet (PECAM-1) endothelial cell adhesion molecule 1, vascular endothelial-cadherin CdH5 (Ca-dependent cell adhesion molecule), vascular endothelial growth factor A, (VEGFA) and insulin-like growth factor 1 (IGF1). Chronic hypoxia did not affect CdH5, but PECAM1 MRNA expressions were increased in control and GDM subjects. Control hypoxic and GDM normoxic VEGFA MRNA expressions and hypoxia-inducible factor 1-alpha (HIF1α) protein expressions were significantly increased in HUCB ECFCs. GDM resulted in most failure of HUCB ECFC adaptation and eNOS protein expressions against chronic hypoxia. Chronic hypoxia resulted in an overall decline in HUCB ECFCs’ proliferative ability due to reduction of clonogenic capacity and diminished vessel formation. Furthermore, GDM also resulted in most failure of cord blood ECFC adaptation against chronic hypoxic environment. PMID:25565870

  4. [Adhesive cutaneous pharmaceutical forms].

    PubMed

    Gafiţanu, E; Matei, I; Mungiu, O C; Pavelescu, M; Mîndreci, I; Apostol, I; Ionescu, G

    1989-01-01

    The adhesive cutaneous pharmaceutical forms aimed to local action release the drug substance in view of a dermatological, traumatological, antirheumatic, cosmetic action. Two such preparations were obtained and their stability, consistency and pH were determined. The "in vitro" tests of their bioavailability revealed the dynamics of calcium ions release according to the associations of each preparation. The bioavailability determined by evaluating the pharmacological response demonstrated the antiinflammatory action obtained by the association of calcium ions with the components extracted from poplar muds. The therapeutical efficiency of the studied preparations has proved in the treatment of some sport injuries.

  5. Puerperal endometritis and intrauterine adhesions.

    PubMed

    Polishuk, W Z; Anteby, S O; Weinstein, D

    1975-08-01

    The role of puerperal endometritis in intrauterine adhesion formation was studied by hysterography in 171 women who had cesarean sections. Of 28 patients who developed significant endometritis, only one developed intracervical adhesions. In the control group of 143 cases, there was also only one such case. Endometritis alone apparently does not play a significant role in intrauterine and endocervical adhesion formation. The possible role of placental fibroblasts in preventing endometrial regeneration is discussed. PMID:1158622

  6. Adhesion properties of gecko setae

    NASA Astrophysics Data System (ADS)

    Hill, Ginel; Peattie, Anne; Daniels, Roxanne; Full, Robert; Kenny, Thomas

    2005-03-01

    Millions of keratin hairs on gecko feet, called setae, act as a spectacular dry adhesive. Each seta branches into hundreds of smaller fibers that terminate in spatula-shaped ends. Morphological differences between the setae from different gecko species are suspected to affect both single-seta and whole-animal adhesion properties. Single-seta adhesive force measurements made using a MEMS piezoresistive cantilever capable of two-axis measurements are presented.

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

    PubMed

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

    2014-10-01

    Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression. PMID

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

    PubMed

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

    2014-10-01

    Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.

  9. Targeting Tumor Necrosis Factor-α with Adalimumab: Effects on Endothelial Activation and Monocyte Adhesion

    PubMed Central

    Oberoi, Raghav; Schuett, Jutta; Schuett, Harald; Koch, Ann-Kathrin; Luchtefeld, Maren

    2016-01-01

    Objective It is well known that atherosclerotic inflammatory vascular disease is critically driven by oxidized lipids and cytokines. In this regard, tumor necrosis factor (TNF)-α is known as a crucial mediator of early pro-atherosclerotic events. Epidemiologic data suggest that blockade of TNF-α has beneficial effects on vascular outcomes in patients with rheumatoid arthritis, however, detailed mechanistic studies are still lacking. This study aims to elucidate effects of TNF-α blockade by adalimumab–which is approved for several inflammatory disorders–on endothelial activation and monocyte adhesion under pro-atherosclerotic conditions. Methods and Results Phorbol myristate acetate (PMA) differentiated THP-1 macrophages were stimulated with oxidized low density lipoprotein and subsequent analysis of this conditioned media (oxLDL CM) revealed a strong release of TNF-α. The TNF-α rich supernatant led to activation of human umbilical vein endothelial cells (HUVEC) as shown by enhanced expression of major adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin which was suppressed by the TNF-α inhibitor adalimumab. Accordingly, adalimumab effectively prevented THP-1 monocyte adhesion to endothelial cells under static as well as under flow conditions. Furthermore, adalimumab suppressed endothelial leakage as shown by Evan's blue diffusion across a confluent endothelial monolayer. Of note, after intraperitoneal injection we detected abundant deposition of fluorophore-labelled adalimumab in atherosclerotic plaques of hypercholesterolemic mice. Conclusion Our results show that adalimumab prevents major inflammatory effects of TNF-α on endothelial activation, endothelial monocyte adhesion, endothelial leakage and therefore extends the therapeutic options of adalimumab to limit vascular inflammation. PMID:27467817

  10. A standardized bamboo leaf extract inhibits monocyte adhesion to endothelial cells by modulating vascular cell adhesion protein-1

    PubMed Central

    Choi, Sunga; Park, Myoung Soo; Lee, Yu Ran; Lee, Young Chul; Kim, Tae Woo; Do, Seon-Gil; Kim, Dong Seon

    2013-01-01

    Bamboo leaves (Phyllostachys pubescens Mazel ex J. Houz (Poacea)) have a long history of food and medical applications in Asia, including Japan and Korea. They have been used as a traditional medicine for centuries. We investigated the mechanism of anti-inflammatory activity of a bamboo leaf extract (BLE) on tumor necrosis factor-alpha (TNF-α)-induced monocyte adhesion in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to BLE did not inhibit cell viability or cause morphological changes at concentrations ranging from 1 µg/ml to 1 mg/ml. Treatment with 0.1 mg/ml BLE caused 63% inhibition of monocyte adhesion in TNF-α-activated HUVECs, which was associated with 38.4% suppression of vascular cell adhesion molecule-1 expression. Furthermore, TNF-α-induced reactive oxygen species generation was decreased to 47.9% in BLE treated TNF-α-activated HUVECs. BLE (0.05 mg/ml) also caused about 50% inhibition of interleukin-6 secretion from lipopolysaccharide-stimulated monocyte. The results indicate that BLE may be clinically useful as an anti-inflammatory or anti-oxidant for human cardiovascular disease including atherosclerosis. PMID:23422838

  11. Polyphenols from Artemisia annua L Inhibit Adhesion and EMT of Highly Metastatic Breast Cancer Cells MDA-MB-231.

    PubMed

    Ko, Young Shin; Lee, Won Sup; Panchanathan, Radha; Joo, Young Nak; Choi, Yung Hyun; Kim, Gon Sup; Jung, Jin-Myung; Ryu, Chung Ho; Shin, Sung Chul; Kim, Hye Jung

    2016-07-01

    Recent evidence suggests that polyphenolic compounds from plants have anti-invasion and anti-metastasis capabilities. The Korean annual weed, Artemisia annua L., has been used as a folk medicine for treatment of various diseases. Here, we isolated and characterized polyphenols from Korean A. annua L (pKAL). We investigated anti-metastatic effects of pKAL on the highly metastatic MDA-MB-231 breast cancer cells especially focusing on cancer cell adhesion to the endothelial cell and epithelial-mesenchymal transition (EMT). Firstly, pKAL inhibited cell viability of MDA-MB-231 cells in a dose-dependent manner, but not that of human umbilical vein endothelial cells (ECs). Polyphenols from Korean A. annua L inhibited the adhesion of MDA-MB-231 cells to ECs through reducing vascular cell adhesion molecule-1 expression of MDA-MB-231 and ECs, but not intracellular adhesion molecule-1 at the concentrations where pKAL did not influence the cell viability of either MDA-MB-231 cells nor EC. Further, pKAL inhibited tumor necrosis factor-activated MDA-MB-231 breast cancer cell invasion through inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 and EMT. Moreover, pKAL inhibited phosphorylation of Akt, but not that of protein kinase C. These results suggest that pKAL may serve as a therapeutic agent against cancer metastasis at least in part by inhibiting the cancer cell adhesion to ECs through suppression of vascular cell adhesion molecule-1 and invasion through suppression of EMT. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27151203

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

    PubMed

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

    2015-11-30

    Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated. PMID:26412140

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

    PubMed

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

    2015-11-30

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

  14. Topographically Tuning Polymer Adhesion

    NASA Astrophysics Data System (ADS)

    Crosby, Alfred

    2003-03-01

    Nature often uses geometry on micro and nano length scales to systematically tailor performance in multivariable environments. A great example, which has received much attention recently, is the foot of a gecko. The gecko's foot is covered with hundreds of thousands of "hair"-like protrusions which dictate a gecko's precise control of adhesion through van der Waals forces.(1) In our research, we fabricate controlled structures ranging from the nano to micro length scales on elastomeric surfaces. Our initial results are based on the topography of spherical caps and high-aspect ratio posts that decorate the surface of polydimethylsiloxane layers. Based on initial calculations, we demonstrate how the aspect ratio and inter-feature spacing greatly affects the near-surface compliance, thus impacting the processes of interface formation. The density and shape of the features are also shown to enhance the prevention of interfacial failure. These results are relevant for the refinement of the soft lithography processing technique, the development of smart adhesives, and the fabrication of bonding sites for biological implants. (1) Autumn, K.; Liang, Y.A.; Hsieh, S.T.; Zesch, W.; Chan, W.P.; Kenny,T.W.; Fearing, R.; Full, R.J. Nature 2000, 405, 681-685.

  15. Principles of adhesion.

    PubMed

    Baier, R E

    1992-01-01

    Understanding interfacial phenomena has been of direct relevance and practical benefit to extending the use of dental adhesives. Both surface physics, which describes properties of the inorganic materials' interfacial zones from their actual phase boundaries toward the bulk phases of the solids, and surface chemistry, which describes phenomena at the solid/biological interface and beyond it into the variable organic environment, have been important. High-energy materials include solids that are very hard, have high melting points, strong intermolecular forces, and basically crystalline structures, such as dental enamel. Low-energy materials, such as dentinal collagen, salivary films, and the organic resins of restorative materials, are softer, lower melting, and have weaker intermolecular forces, poorer crystallinity, and surface energies generally less than 100 ergs/cm. It has been a properly renewed emphasis on wetting of dental surfaces and their modification by primer coats, displacing or mixing with water and adsorbed proteinaceous films, that has promoted the success of many recently developed fourth-generation dentin adhesives. Their improved wettability for biological phases correlates directly with their better infiltration and anchoring of composites.

  16. Analysis and testing of adhesive bonds

    NASA Technical Reports Server (NTRS)

    Anderson, G. P.; Bennett, S. J.; Devries, K. L.

    1977-01-01

    An adhesive fracture mechanics approach is described with reference to the identification and design of the best tests for evaluating a given adhesive, the definition of the most meaningful fundamental parameters by which adhesives might be characterized, and the application of these parameters to the design of joints and to the prediction of their performance. Topics include standard adhesive test techniques, the theory of adhesive fracture, and adhesive fracture energy tests. Analytical methods and computer techniques for adhesive bonding, chemical and physical aspects of adhesive fracture, and specific applications and aspects of adhesive fracture mechanics are discussed.

  17. Stickiness--some fundamentals of adhesion.

    PubMed

    Gay, Cyprien

    2002-12-01

    We review some adhesion mechanisms that have been understood in the field of synthetic adhesives, and more precisely for adhesives that adhere instantaneously (a property named tackiness) and whose adhesive strength usually depends on the applied pressure (pressure-sensitive adhesives). The discussion includes effects of surface roughness, elasticity, cavitation, viscous and elastic fingering, substrate flexibility. PMID:21680396

  18. Stickiness--some fundamentals of adhesion.

    PubMed

    Gay, Cyprien

    2002-12-01

    We review some adhesion mechanisms that have been understood in the field of synthetic adhesives, and more precisely for adhesives that adhere instantaneously (a property named tackiness) and whose adhesive strength usually depends on the applied pressure (pressure-sensitive adhesives). The discussion includes effects of surface roughness, elasticity, cavitation, viscous and elastic fingering, substrate flexibility.

  19. Prolonged Morphine Exposure Induces Increased Firm Adhesion in an in Vitro Model of the Blood–Brain Barrier

    PubMed Central

    Strazza, Marianne; Pirrone, Vanessa; Wigdahl, Brian; Dampier, Will; Lin, Wei; Feng, Rui; Maubert, Monique E.; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Nonnemacher, Michael R.

    2016-01-01

    The blood–brain barrier (BBB) has been defined as a critically important protective barrier that is involved in providing essential biologic, physiologic, and immunologic separation between the central nervous system (CNS) and the periphery. Insults to the BBB can cause overall barrier damage or deregulation of the careful homeostasis maintained between the periphery and the CNS. These insults can, therefore, yield numerous phenotypes including increased overall permeability, interendothelial gap formation, alterations in cytokine and chemokine secretion, and accelerated cellular passage. The current studies expose the human brain microvascular endothelial cell line, hCMEC/D3, to prolonged morphine exposure and aim to uncover the mechanisms underlying alterations in barrier function in vitro. These studies show alterations in the mRNA and protein levels of the cellular adhesion molecules (CAMs) intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and activated leukocyte cell adhesion molecule that correlate with an increased firm adhesion of the CD3+ subpopulation of peripheral blood mononuclear cells (PBMCs). Overall, these studies suggest that prolonged morphine exposure may result in increased cell migration into the CNS, which may accelerate pathological processes in many diseases that involve the BBB. PMID:27294916

  20. Effect of adhesive thickness on adhesively bonded T-joint

    NASA Astrophysics Data System (ADS)

    Abdullah, A. R.; Afendi, Mohd; Majid, M. S. Abdul

    2013-12-01

    The aim of this work is to analyze the effect of adhesive thickness on tensile strength of adhesively bonded stainless steel T-joint. Specimens were made from SUS 304 Stainless Steel plate and SUS 304 Stainless Steel perforated plate. Four T-joint specimens with different adhesive thicknesses (0.5, 1.0, 1.5 and 2.0 mm) were made. Experiment result shows T-joint specimen with adhesive thickness of 1.0 mm yield highest maximum load. Identical T-joint specimen jointed by spot welding was also tested. Tensile test shows welded T-Joint had eight times higher tensile load than adhesively bonded T-joint. However, in low pressure application such as urea granulator chamber, high tensile strength is not mandatory. This work is useful for designer in fertilizer industry and others who are searching for alternative to spot welding.

  1. Improved Adhesion and Compliancy of Hierarchical Fibrillar Adhesives.

    PubMed

    Li, Yasong; Gates, Byron D; Menon, Carlo

    2015-08-01

    The gecko relies on van der Waals forces to cling onto surfaces with a variety of topography and composition. The hierarchical fibrillar structures on their climbing feet, ranging from mesoscale to nanoscale, are hypothesized to be key elements for the animal to conquer both smooth and rough surfaces. An epoxy-based artificial hierarchical fibrillar adhesive was prepared to study the influence of the hierarchical structures on the properties of a dry adhesive. The presented experiments highlight the advantages of a hierarchical structure despite a reduction of overall density and aspect ratio of nanofibrils. In contrast to an adhesive containing only nanometer-size fibrils, the hierarchical fibrillar adhesives exhibited a higher adhesion force and better compliancy when tested on an identical substrate.

  2. Stretchable, adhesion-tunable dry adhesive by surface wrinkling.

    PubMed

    Jeong, Hoon Eui; Kwak, Moon Kyu; Suh, Kahp Y

    2010-02-16

    We introduce a simple yet robust method of fabricating a stretchable, adhesion-tunable dry adhesive by combining replica molding and surface wrinkling. By utilizing a thin, wrinkled polydimethyl siloxane (PDMS) sheet with a thickness of 1 mm with built-in micropillars, active, dynamic control of normal and shear adhesion was achieved. Relatively strong normal (approximately 10.8 N/cm(2)) and shear adhesion (approximately 14.7 N/cm(2)) forces could be obtained for a fully extended (strained) PDMS sheet (prestrain of approximately 3%), whereas the forces could be rapidly reduced to nearly zero once the prestrain was released (prestrain of approximately 0.5%). Moreover, durability tests demonstrated that the adhesion strength in both the normal and shear directions was maintained over more than 100 cycles of attachment and detachment.

  3. Electrical detection of kidney injury molecule-1 with AlGaN /GaN high electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Wang, H. T.; Kang, B. S.; Ren, F.; Pearton, S. J.; Johnson, J. W.; Rajagopal, P.; Roberts, J. C.; Piner, E. L.; Linthicum, K. J.

    2007-11-01

    AlGaN /GaN high electron mobility transistors (HEMTs) were used to detect kidney injury molecule-1 (KIM-1), an important biomarker for early kidney injury detection. The gate region consisted of 5nm gold deposited onto the AlGaN surface. The gold was conjugated to highly specific KIM-1 antibodies through a self-assembled monolayer of thioglycolic acid. The HEMT source-drain current showed a clear dependence on the KIM-1 concentration in phosphate-buffered saline solution. The limit of detection was 1ng/ml using a 20×50μm2 gate sensing area. This approach shows potential for both preclinical and clinical kidney injury diagnosis with accurate, rapid, noninvasive, and high throughput capabilities.

  4. Electrical detection of kidney injury molecule-1 with AlGaN/GaN high electron mobility transistors

    SciTech Connect

    Wang, H. T.; Kang, B. S.; Ren, F.; Pearton, S. J.; Johnson, J. W.; Rajagopal, P.; Roberts, J. C.; Piner, E. L.; Linthicum, K. J.

    2007-11-26

    AlGaN/GaN high electron mobility transistors (HEMTs) were used to detect kidney injury molecule-1 (KIM-1), an important biomarker for early kidney injury detection. The gate region consisted of 5 nm gold deposited onto the AlGaN surface. The gold was conjugated to highly specific KIM-1 antibodies through a self-assembled monolayer of thioglycolic acid. The HEMT source-drain current showed a clear dependence on the KIM-1 concentration in phosphate-buffered saline solution. The limit of detection was 1 ng/ml using a 20x50 {mu}m{sup 2} gate sensing area. This approach shows potential for both preclinical and clinical kidney injury diagnosis with accurate, rapid, noninvasive, and high throughput capabilities.

  5. Fire-Retardant Epoxy Adhesives

    NASA Technical Reports Server (NTRS)

    Bilow, N.; Giants, T. W.

    1982-01-01

    Phosphorus-containing epoxy is fire-retardant and translucent. Intended as adhesive for laminated plastic sheets, new material bonds well to titanium dioxide-filled plastic film, which ordinarily shows little surface interaction with adhesives. Fire retardancy has been demonstrated, and smoke density is low enough to avoid smoke obscuration.

  6. Platelet adhesiveness in diabetes mellitus

    PubMed Central

    Shaw, S.; Pegrum, G. D.; Wolff, Sylvia; Ashton, W. L.

    1967-01-01

    Platelet adhesiveness has been assessed on whole blood from a series of 34 diabetics and 50 control subjects using adenosine diphosphate (A.D.P.) and by adherence to glass microspherules (ballotini). Using both techniques it was possible to demonstrate a significant increase in platelet adhesiveness in the diabetic patients. PMID:5614070

  7. 21 CFR 880.5240 - Medical adhesive tape and adhesive bandage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical adhesive tape and adhesive bandage. 880... Personal Use Therapeutic Devices § 880.5240 Medical adhesive tape and adhesive bandage. (a) Identification. A medical adhesive tape or adhesive bandage is a device intended for medical purposes that...

  8. 21 CFR 880.5240 - Medical adhesive tape and adhesive bandage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical adhesive tape and adhesive bandage. 880... Personal Use Therapeutic Devices § 880.5240 Medical adhesive tape and adhesive bandage. (a) Identification. A medical adhesive tape or adhesive bandage is a device intended for medical purposes that...

  9. 21 CFR 880.5240 - Medical adhesive tape and adhesive bandage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical adhesive tape and adhesive bandage. 880... Personal Use Therapeutic Devices § 880.5240 Medical adhesive tape and adhesive bandage. (a) Identification. A medical adhesive tape or adhesive bandage is a device intended for medical purposes that...

  10. 21 CFR 880.5240 - Medical adhesive tape and adhesive bandage.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical adhesive tape and adhesive bandage. 880... Personal Use Therapeutic Devices § 880.5240 Medical adhesive tape and adhesive bandage. (a) Identification. A medical adhesive tape or adhesive bandage is a device intended for medical purposes that...

  11. Epidural Lysis of Adhesions

    PubMed Central

    Lee, Frank; Jamison, David E.; Hurley, Robert W.

    2014-01-01

    As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. PMID:24478895

  12. Adhesion testing device

    NASA Technical Reports Server (NTRS)

    LaPeyronnie, Glenn M. (Inventor); Huff, Charles M. (Inventor)

    2010-01-01

    The present invention provides a testing apparatus and method for testing the adhesion of a coating to a surface. The invention also includes an improved testing button or dolly for use with the testing apparatus and a self aligning button hook or dolly interface on the testing apparatus. According to preferred forms, the apparatus and method of the present invention are simple, portable, battery operated rugged, and inexpensive to manufacture and use, are readily adaptable to a wide variety of uses, and provide effective and accurate testing results. The device includes a linear actuator driven by an electric motor coupled to the actuator through a gearbox and a rotatable shaft. The electronics for the device are contained in the head section of the device. At the contact end of the device, is positioned a self aligning button hook, attached below the load cell located on the actuator shaft.

  13. Corrugated pipe adhesive applicator apparatus

    DOEpatents

    Shirey, R.A.

    1983-06-14

    Apparatus for coating selected portions of the troughs of a corrugated pipe with an adhesive includes a support disposed within the pipe with a reservoir containing the adhesive disposed on the support. A pump, including a spout, is utilized for supplying the adhesive from the reservoir to a trough of the pipe. A rotatable applicator is supported on the support and contacts the trough of the pipe. The applicator itself is sized so as to fit within the trough, and contacts the adhesive in the trough and spreads the adhesive in the trough upon rotation. A trough shield, supported by the support and disposed in the path of rotation of the applicator, is utilized to prevent the applicator from contacting selected portions of the trough. A locator head is also disposed on the support and provides a way for aligning the spout, the applicator, and the trough shield with the trough. 4 figs.

  14. Biological adhesives and fastening devices

    NASA Astrophysics Data System (ADS)

    Wolpert, H. D.

    2012-04-01

    Sea creatures are a leading source to some of the more interesting discoveries in adhesives. Because sea water naturally breaks down even the strongest conventional adhesive, an alternative is important that could be used in repairing or fabricating anything that might have regular contact with moisture such as: Repairing broken and shattered bones, developing a surgical adhesive, use in the dental work, repairing and building ships, and manufacturing plywood. Some of nature's prototypes include the common mussel, limpet, some bacteria and abalone. As we learn more about these adhesives we are also developing non adhesive fasteners, such as mimicked after studying the octopus, burdock burrs (i.e. Velcro®) and the gecko.

  15. Corrugated pipe adhesive applicator apparatus

    DOEpatents

    Shirey, Ray A.

    1983-06-14

    Apparatus for coating selected portions of the troughs of a corrugated pipe within an adhesive includes a support disposed within the pipe with a reservoir containing the adhesive disposed on the support. A pump, including a spout, is utilized for supplying the adhesive from the reservoir to a trough of the pipe. A rotatable applicator is supported on the support and contacts the trough of the pipe. The applicator itself is sized so as to fit within the trough, and contacts the adhesive in the trough and spreads the adhesive in the trough upon rotation. A trough shield, supported by the support and disposed in the path of rotation of the applicator, is utilized to prevent the applicator from contacting selected portions of the trough. A locator head is also disposed on the support and provides a way for aligning the spout, the applicator, and the trough shield with the trough.

  16. Neutrophil adhesion in leukocyte adhesion deficiency syndrome type 2.

    PubMed Central

    Phillips, M L; Schwartz, B R; Etzioni, A; Bayer, R; Ochs, H D; Paulson, J C; Harlan, J M

    1995-01-01

    We have previously reported a newly discovered congenital disorder of neutrophil adhesion, leukocyte adhesion deficiency syndrome type 2 (LAD II). The clinical manifestations of this syndrome are similar to those seen in the classic leukocyte adhesion deficiency syndrome, now designated type 1 (LAD I), but the two syndromes differ in the molecular basis of their adhesion defects. LAD I is caused by a deficiency in the CD18 integrin adhesion molecules while LAD II patients are deficient in expression of sialyl-Lewis X (SLeX), a carbohydrate ligand for selectins. In this report we demonstrate that neutrophils from a LAD II patient bind minimally or not at all to recombinant E-selectin, purified platelet P-selectin, or P-selectin expressed on histamine-activated human umbilical vein endothelial cells, but have normal levels of L-selectin and CD11b/CD18 integrin, and adhere to and migrate across endothelium when CD11b/CD18 is activated. We compare LAD I and LAD II patient neutrophil function in vitro, demonstrating that integrin and selectin adhesion molecules have distinct but interdependent roles in neutrophil adhesion during an inflammatory response. Images PMID:8675661

  17. Enhanced adhesion by gecko-inspired hierarchical fibrillar adhesives.

    PubMed

    Murphy, Michael P; Kim, Seok; Sitti, Metin

    2009-04-01

    The complex structures that allow geckos to repeatably adhere to surfaces consist of multilevel branching fibers with specialized tips. We present a novel technique for fabricating similar multilevel structures from polymer materials and demonstrate the fabrication of arrays of two- and three-level structures, wherein each level terminates in flat mushroom-type tips. Adhesion experiments are conducted on two-level fiber arrays on a 12-mm-diameter glass hemisphere, which exhibit both increased adhesion and interface toughness over one-level fiber samples and unstructured control samples. These adhesion enhancements are the result of increased surface conformation as well as increased extension during detachment.

  18. Wet Adhesion and Adhesive Locomotion of Snails on Anti-Adhesive Non-Wetting Surfaces

    PubMed Central

    Shirtcliffe, Neil J.; McHale, Glen; Newton, Michael I.

    2012-01-01

    Creating surfaces capable of resisting liquid-mediated adhesion is extremely difficult due to the strong capillary forces that exist between surfaces. Land snails use this to adhere to and traverse across almost any type of solid surface of any orientation (horizontal, vertical or inverted), texture (smooth, rough or granular) or wetting property (hydrophilic or hydrophobic) via a layer of mucus. However, the wetting properties that enable snails to generate strong temporary attachment and the effectiveness of this adhesive locomotion on modern super-slippy superhydrophobic surfaces are unclear. Here we report that snail adhesion overcomes a wide range of these microscale and nanoscale topographically structured non-stick surfaces. For the one surface which we found to be snail resistant, we show that the effect is correlated with the wetting response of the surface to a weak surfactant. Our results elucidate some critical wetting factors for the design of anti-adhesive and bio-adhesion resistant surfaces. PMID:22693563

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

    PubMed

    Eschen, Ole; Christensen, Jeppe Hagstrup; Dethlefsen, Claus; Schmidt, Erik Berg

    2008-01-01

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

  20. The role of soluble cell adhesion molecules in patients with suspected deep vein thrombosis.

    PubMed

    Bucek, Robert A; Reiter, Markus; Quehenberger, Peter; Minar, Erich; Baghestanian, Mehrdad

    2003-10-01

    Activation of the endothelium, platelets and leukocytes has been shown to play an important role in the aetiology of deep venous thrombosis (DVT) in in-vitro experiments, resulting in the release of soluble cell adhesion molecules (sCAMs). We therefore assessed the value of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin and soluble P-selectin for the diagnostic process in 69 consecutive patients with suspected DVT. Final diagnosis was based on the results of Duplex sonography or ascending venography. Thirty-seven patients (53.6%) finally suffered from DVT. Mean levels of sVCAM-1 were 589 +/- 530 ng/ml for controls and 587 +/- 328 ng/ml for patients. Corresponding levels concerning sICAM-1 were 316 +/- 161 and 342 +/- 186 ng/ml, those concerning soluble E-selectin were 54 +/- 38 and 42 +/- 18 ng/ml, and those concerning soluble P-selectin were 94 +/- 37 and 99 +/- 36 ng/ml (all P > 0.05). There was no significant correlation of the thrombus extension (all P > 0.05) or the duration of symptoms with sCAMs (all P > 0.05). In conclusion, we detected no significant differences concerning the concentration of four major sCAMs between patients with DVT and controls, so their assessment does not add any useful information for the diagnostic process of DVT.

  1. Differential Associations between CDH13 Genotypes, Adiponectin Levels, and Circulating Levels of Cellular Adhesive Molecules

    PubMed Central

    Teng, Ming-Sheng; Wu, Semon; Hsu, Lung-An; Chou, Hsin-Hua; Ko, Yu-Lin

    2015-01-01

    CDH13 gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between CDH13 locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the CDH13 rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all P < 0.05). In a subgroup analysis stratified by sex, significant associations between CDH13 genotypes and sE-selectin levels occurred only in men (P = 3.9 × 10−4 and interaction P = 0.005). CDH13 locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and CDH13 gene variants in immune-mediated and inflammatory diseases. PMID:26600672

  2. Kindlin-3 regulates integrin activation and adhesion reinforcement of effector T cells.

    PubMed

    Moretti, Federico A; Moser, Markus; Lyck, Ruth; Abadier, Michael; Ruppert, Raphael; Engelhardt, Britta; Fässler, Reinhard

    2013-10-15

    Activated T cells use very late antigen-4/α4β1 integrin for capture, rolling on, and firm adhesion to endothelial cells, and use leukocyte function-associated antigen-1/αLβ2 integrin for subsequent crawling and extravasation. Inhibition of α4β1 is sufficient to prevent extravasation of activated T cells and is successfully used to combat autoimmune diseases, such as multiple sclerosis. Here we show that effector T cells lacking the integrin activator Kindlin-3 extravasate and induce experimental autoimmune encephalomyelitis in mice immunized with autoantigen. In sharp contrast, adoptively transferred autoreactive T cells from Kindlin-3-deficient mice fail to extravasate into the naïve CNS. Mechanistically, autoreactive Kindlin-3-null T cells extravasate when the CNS is inflamed and the brain microvasculature expresses high levels of integrin ligands. Flow chamber assays under physiological shear conditions confirmed that Kindlin-3-null effector T cells adhere to high concentrations of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, albeit less efficiently than WT T cells. Although these arrested T cells polarize and start crawling, only few remain firmly adherent over time. Our data demonstrate that the requirement of Kindlin-3 for effector T cells to induce α4β1 and αLβ2 integrin ligand binding and stabilization of integrin-ligand bonds is critical when integrin ligand levels are low, but of less importance when integrin ligand levels are high. PMID:24089451

  3. Choice of anesthetic technique on plasma concentrations of interleukins and cell adhesion molecules

    PubMed Central

    2013-01-01

    Background Whether inflammatory responses to surgery are comparably activated during total intravenous anesthesia (TIVA) and during volatile anesthesia remains unclear. We thus compared the perioperative effects of TIVA and isoflurane anesthesia on plasma concentrations of proinflammatory and anti-inflammatory interleukins and cell adhesion molecules. Methods Patients having laparoscopic cholecystectomies were randomly allocated to two groups: 44 were assigned to TIVA and 44 to isoflurane anesthesia. IL-1β, IL-6, IL-8, IL-10, IL-13, and the cellular adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were determined preoperatively, before incision, and at 2 and 24 hours postoperatively. Our primary outcomes were area-under-the-curve cytokine and adhesion molecule concentrations over 24 postoperative hours. Results The only statistically significant difference in area-under-the-curve concentrations was for IL-6, which was greater in patients given isoflurane:78 (95% confidence interval (CI): 52 to 109) pg/ml versus 33 (22 to 50) pg/ml, P= 0.006. Two hours after surgery, IL-6 was significantly greater than baseline in patients assigned to isoflurane: 47 (95% CI: 4 to 216, P<0.001) pg/ml versus 18 (95%CI: 4 to 374, P<0.001) pg/ml in the TIVA group. In contrast, IL-10 was significantly greater in patients assigned to TIVA: 20 (95% CI: 2 to 140, P<0.001) pg/ml versus 12 (95% CI: 3 to 126, P<0.001) pg/ml. By 24 hours after surgery, concentrations were generally similar between study groups and similar to baseline values. Conclusion The only biomarker whose postoperative area-under-the-curve concentrations differed significantly as a function of anesthetic management was IL-6. Two hours after surgery, IL-6 concentrations were significantly greater in patients given isoflurane than TIVA. However, the differences were modest and seem unlikely to prove clinically important. Further studies are needed. PMID:24472144

  4. Marine Bioinspired Underwater Contact Adhesion.

    PubMed

    Clancy, Sean K; Sodano, Antonio; Cunningham, Dylan J; Huang, Sharon S; Zalicki, Piotr J; Shin, Seunghan; Ahn, B Kollbe

    2016-05-01

    Marine mussels and barnacles are sessile biofouling organisms that adhere to a number of surfaces in wet environments and maintain remarkably strong bonds. Previous synthetic approaches to mimic biological wet adhesive properties have focused mainly on the catechol moiety, present in mussel foot proteins (mfps), and especially rich in the interfacial mfps, for example, mfp-3 and -5, found at the interface between the mussel plaque and substrate. Barnacles, however, do not use Dopa for their wet adhesion, but are instead rich in noncatecholic aromatic residues. Due to this anomaly, we were intrigued to study the initial contact adhesion properties of copolymerized acrylate films containing the key functionalities of barnacle cement proteins and interfacial mfps, for example, aromatic (catecholic or noncatecholic), cationic, anionic, and nonpolar residues. The initial wet contact adhesion of the copolymers was measured using a probe tack testing apparatus with a flat-punch contact geometry. The wet contact adhesion of an optimized, bioinspired copolymer film was ∼15.0 N/cm(2) in deionized water and ∼9.0 N/cm(2) in artificial seawater, up to 150 times greater than commercial pressure-sensitive adhesive (PSA) tapes (∼0.1 N/cm(2)). Furthermore, maximum wet contact adhesion was obtained at ∼pH 7, suggesting viability for biomedical applications. PMID:27046671

  5. Osteoblast adhesion on nanophase ceramics.

    PubMed

    Webster, T J; Siegel, R W; Bizios, R

    1999-07-01

    Osteoblast adhesion on nanophase alumina (Al2O3) and titania (TiO2) was investigated in vitro. Osteoblast adhesion to nanophase alumina and titania in the absence of serum from Dulbecco's modified Eagle medium (DMEM) was significantly (P < 0.01) less than osteoblast adhesion to alumina and titania in the presence of serum. In the presence of 10% fetal bovine serum in DMEM osteoblast adhesion on nanophase alumina (23 nm grain size) and titania (32 nm grain size) was significantly (P < 0.05) greater than on conventional alumina (177 nm grain size) and titania (2.12 microm grain size), respectively, after 1, 2, and 4 h. Further investigation of the dependence of osteoblast adhesion on alumina and titania grain size indicated the presence of a critical grain size for osteoblast adhesion between 49 and 67 nm for alumina and 32 and 56 nm for titania. The present study provides evidence of the ability of nanophase alumina and titania to simulate material characteristics (such as surface grain size) of physiological bone that enhance protein interactions (such as adsorption, configuration, bioactivity, etc.) and subsequent osteoblast adhesion.

  6. Anti-CD31 delays platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arterioles.

    PubMed

    Rosenblum, W I; Murata, S; Nelson, G H; Werner, P K; Ranken, R; Harmon, R C

    1994-07-01

    The arterioles on the surface of the mouse brain (pial arterioles) were observed by in vivo microscopy. A focus of minor endothelial damage was produced in a single pial arteriole in each mouse by briefly exposing the site to a helium neon laser after an intravenous injection of Evans blue. Mice were injected 10 minutes before injury with a monoclonal antibody (MAb) to mouse CD31, also known as platelet endothelial cell adhesion molecule. This treatment doubled (P < .01) the time required for the laser to produce a recognizable platelet aggregate. In additional experiments, an MAb to mouse CD61 and an MAb to mouse intercellular adhesion molecule 1 had no effect. The data support previous observations indicating that platelet adhesion/aggregation in this model is induced by endothelial injury without exposure of basal lamina. The data are consistent with the hypothesis that the endothelial injury exposes or activates a platelet endothelial cell adhesion molecule on the endothelium which is blocked by the MAb directed against CD31. This may be the first demonstration of an effect of an anti-platelet endothelial cell adhesion molecule on platelet endothelial cell adhesion molecule on platelet adhesion/aggregation in vivo. PMID:8030753

  7. Adhesives from modified soy protein

    DOEpatents

    Sun, Susan; Wang, Donghai; Zhong, Zhikai; Yang, Guang

    2008-08-26

    The, present invention provides useful adhesive compositions having similar adhesive properties to conventional UF and PPF resins. The compositions generally include a protein portion and modifying ingredient portion selected from the group consisting of carboxyl-containing compounds, aldehyde-containing compounds, epoxy group-containing compounds, and mixtures thereof. The composition is preferably prepared at a pH level at or near the isoelectric point of the protein. In other preferred forms, the adhesive composition includes a protein portion and a carboxyl-containing group portion.

  8. Foreign material in postoperative adhesions.

    PubMed Central

    Luijendijk, R W; de Lange, D C; Wauters, C C; Hop, W C; Duron, J J; Pailler, J L; Camprodon, B R; Holmdahl, L; van Geldorp, H J; Jeekel, J

    1996-01-01

    OBJECTIVE: The authors determined the prevalence of foreign body granulomas in intra-abdominal adhesions in patients with a history of abdominal surgery. PATIENTS AND METHODS: In a cross-sectional, multicenter, multinational study, adult patients with a history of one or more previous abdominal operations and scheduled for laparotomy between 1991 and 1993 were examined during surgery. Patients in whom adhesions were present were selected for study. Quantity, distribution, and quality of adhesions were scored, and adhesion samples were taken for histologic examination. RESULTS: In 448 studied patients, the adhesions were most frequently attached to the omentum (68%) and the small bowel (67%). The amount of adhesions was significantly smaller in patients with a history of only one minor operation or one major operation, compared with those with multiple laparotomies (p < 0.001). Significantly more adhesions were found in patients with a history of adhesions at previous laparotomy (p < 0.001), with presence of abdominal abscess, hematoma, and intestinal leakage as complications after former surgery (p = 0.01, p = 0.002, and p < 0.001, respectively), and with a history of an unoperated inflammatory process (p = 0.04). Granulomas were found in 26% of all patients. Suture granulomas were found in 25% of the patients. Starch granulomas were present in 5% of the operated patients whose surgeons wore starch-containing gloves. When suture granulomas were present, the median interval between the present and the most recent previous laparotomy was 13 months. When suture granulomas were absent, this interval was significantly longer--i.e., 30 months (p = 0.002). The percentage of patients with suture granulomas decreased gradually from 37% if the previous laparotomy had occurred up to 6 months before the present operation, to 18% if the previous laparotomy had occurred more than 2 years ago (p < 0.001). CONCLUSIONS: The number of adhesions found at laparotomy was significantly

  9. Interfacial adhesion of carbon fibers

    NASA Technical Reports Server (NTRS)

    Bascom, Willard D.

    1987-01-01

    Relative adhesion strengths between AS4, AS1, and XAS carbon fibers and thermoplastic polymers were determined using the embedded single filament test. Polymers studied included polycarbonate, polyphenylene oxide, polyetherimide, polysulfone, polyphenylene oxide blends with polystyrene, and polycarbonate blends with a polycarbonate polysiloxane block copolymer. Fiber surface treatments and sizings improved adhesion somewhat, but adhesion remained well below levels obtained with epoxy matrices. An explanation for the differences between the Hercules and Grafil fibers was sought using X ray photon spectroscopy, wetting, scanning electron microscopy and thermal desorption analysis.

  10. Notch-Mediated Cell Adhesion

    PubMed Central

    Murata, Akihiko; Hayashi, Shin-Ichi

    2016-01-01

    Notch family members are generally recognized as signaling molecules that control various cellular responses in metazoan organisms. Early fly studies and our mammalian studies demonstrated that Notch family members are also cell adhesion molecules; however, information on the physiological roles of this function and its origin is limited. In this review, we discuss the potential present and ancestral roles of Notch-mediated cell adhesion in order to explore its origin and the initial roles of Notch family members dating back to metazoan evolution. We hypothesize that Notch family members may have initially emerged as cell adhesion molecules in order to mediate multicellularity in the last common ancestor of metazoan organisms. PMID:26784245

  11. Photovoltaic module with adhesion promoter

    DOEpatents

    Xavier, Grace

    2013-10-08

    Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.

  12. Advances in light curing adhesives

    NASA Astrophysics Data System (ADS)

    Bachmann, Andy

    2001-11-01

    This paper describes the development of a new family of light curing adhesives containing a new reactive additive previously not used in optical grade light curing adhesives are obtained with the addition of functionalized cellulositics. Outgassing as low as 10-6 grams/gram has been observed based on headspace sampling. Other additives have lowered the shrinkage rates of positioning adhesives from near 1 percent to less than 0.1 percent with fractional, percentage movements over thermal range of -40 degrees C to +200 degrees C.

  13. Wear mechanism based on adhesion

    NASA Technical Reports Server (NTRS)

    Yamamoto, T.; Buckley, D. H.

    1982-01-01

    Various concepts concerning wear mechanisms and deformation behavior observed in the sliding wear track are surveyed. The mechanisms for wear fragment formation is discussed on the basis of adhesion. The wear process under unlubricated sliding conditions is explained in relation to the concept of adhesion at the interface during the sliding process. The mechanism for tearing away the surface layer from the contact area and forming the sliding track contour is explained by assuming the simplified process of material removal based on the adhesion theory.

  14. Artemisinin inhibits monocyte adhesion to HUVECs through the NF-κB and MAPK pathways in vitro.

    PubMed

    Wang, Yue; Cao, Jiatian; Fan, Yuqi; Xie, Yushui; Xu, Zuojun; Yin, Zhaofang; Gao, Lin; Wang, Changqian

    2016-06-01

    The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) plays a crucial role in the initiation of atherosclerosis. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important molecules involved in the adhesion of monocytes to HUVECs. Previous studies have suggested that artemisinin, apart from an anti-malarial agent, also has other effects. In the present study, we found that artemisinin significantly decreased the adhesion of monocytes to tumor necrosis factor-α (TNF-α)-stimulated HUVECs in a dose-dependent manner and suppressed the mRNA and protein level of ICAM-1 and VCAM-1 in the TNF-α-stimulated HUVECs. In addition, the nuclear factor-κB (NF-κB) inhibitor, Bay 11-7082, and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and U0126) respectively reduced the adhesion of monocytes to TNF-α-stimulated HUVECs, and suppressed ICAM-1 and VCAM-1 expression in TNF-α stimulated HUVECs. Moreover, artemisinin impeded the activation of the NF-κB and MAPK signaling pathways. Furthermore, Bay 11-7082 significantly decreased the phosphorylation of levels extracellular signal-regulated protein kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK). Taken together, the findings of our study indicated that artemisinin blocked monocyte adhesion to TNF-α-stimulated to HUVECs by downregulating ICAM-1 and VCAM-1 expression in the TNF-α-stimulated HUVECs. Artemisinin may thus have potential for use in the protection against the early development of atherosclerotic lesions. PMID:27122190

  15. Artemisinin inhibits monocyte adhesion to HUVECs through the NF-κB and MAPK pathways in vitro

    PubMed Central

    WANG, YUE; CAO, JIATIAN; FAN, YUQI; XIE, YUSHUI; XU, ZUOJUN; YIN, ZHAOFANG; GAO, LIN; WANG, CHANGQIAN

    2016-01-01

    The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) plays a crucial role in the initiation of atherosclerosis. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important molecules involved in the adhesion of monocytes to HUVECs. Previous studies have suggested that artemisinin, apart from an anti-malarial agent, also has other effects. In the present study, we found that artemisinin significantly decreased the adhesion of monocytes to tumor necrosis factor-α (TNF-α)-stimulated HUVECs in a dose-dependent manner and suppressed the mRNA and protein level of ICAM-1 and VCAM-1 in the TNF-α-stimulated HUVECs. In addition, the nuclear factor-κB (NF-κB) inhibitor, Bay 11-7082, and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and U0126) respectively reduced the adhesion of monocytes to TNF-α-stimulated HUVECs, and suppressed ICAM-1 and VCAM-1 expression in TNF-α stimulated HUVECs. Moreover, artemisinin impeded the activation of the NF-κB and MAPK signaling pathways. Furthermore, Bay 11-7082 significantly decreased the phosphorylation of levels extracellular signal-regulated protein kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK). Taken together, the findings of our study indicated that artemisinin blocked monocyte adhesion to TNF-α-stimulated to HUVECs by downregulating ICAM-1 and VCAM-1 expression in the TNF-α-stimulated HUVECs. Artemisinin may thus have potential for use in the protection against the early development of atherosclerotic lesions. PMID:27122190

  16. Sargaquinoic Acid Inhibits TNF-α-Induced NF-κB Signaling, Thereby Contributing to Decreased Monocyte Adhesion to Human Umbilical Vein Endothelial Cells (HUVECs).

    PubMed

    Gwon, Wi-Gyeong; Lee, Bonggi; Joung, Eun-Ji; Choi, Min-Woo; Yoon, Nayoung; Shin, Taisun; Oh, Chul-Woong; Kim, Hyeung-Rak

    2015-10-21

    Sargaquinoic acid (SQA) has been known for its antioxidant and anti-inflammatory properties. This study investigated the effects of SQA isolated from Sargassum serratifolium on the inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). SQA decreased the expression of cell adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 as well as chemotactic cytokines such as interleukin-8 and monocyte chemoattractant protein-1 in TNF-α-treated HUVECs. As a result, SQA prevented monocyte adhesion to TNF-α-induced adhesion. SQA also inhibited TNF-α-induced nuclear factor kappa B (NF-κB) translocation into the nucleus by preventing proteolytic degradation of inhibitor κB-α. Overall, SQA protects against TNF-α-induced vascular inflammation through inhibition of the NF-κB pathway in HUVECs. These data suggest that SQA may be used as a therapeutic agent for vascular inflammatory diseases such as atherosclerosis. PMID:26437568

  17. Rolling adhesion of alphaL I domain mutants decorrelated from binding affinity.

    PubMed

    Pepper, Lauren R; Hammer, Daniel A; Boder, Eric T

    2006-06-30

    Activated lymphocyte function-associated antigen-1 (LFA-1, alphaLbeta2 integrin) found on leukocytes facilitates firm adhesion to endothelial cell layers by binding to intercellular adhesion molecule-1 (ICAM-1), which is up-regulated on endothelial cells at sites of inflammation. Recent work has shown that LFA-1 in a pre-activation, low-affinity state may also be involved in the initial tethering and rolling phase of the adhesion cascade. The inserted (I) domain of LFA-1 contains the ligand-binding epitope of the molecule, and a conformational change in this region during activation increases ligand affinity. We have displayed wild-type I domain on the surface of yeast and validated expression using I domain specific antibodies and flow cytometry. Surface display of I domain supports yeast rolling on ICAM-1-coated surfaces under shear flow. Expression of a locked open, high-affinity I domain mutant supports firm adhesion of yeast, while yeast displaying intermediate-affinity I domain mutants exhibit a range of rolling phenotypes. We find that rolling behavior for these mutants fails to correlate with ligand binding affinity. These results indicate that unstressed binding affinity is not the only molecular property that determines adhesive behavior under shear flow.

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

    PubMed Central

    Ashander, Liam M.; Appukuttan, Binoy; Ma, Yuefang; Gardner-Stephen, Dione; Smith, Justine R.

    2016-01-01

    Targeting the endothelial adhesion molecules that control leukocyte trafficking into a tissue has been explored as a biological therapy for inflammatory diseases. However, these molecules also participate in leukocyte migration for immune surveillance, and inhibiting the physiological level of an adhesion molecule might promote infection or malignancy. We explored the concept of targeting endothelial adhesion molecule transcription during inflammation in a human system. Intercellular adhesion molecule 1 (ICAM-1) mediates leukocyte migration across the retinal endothelium in noninfectious posterior uveitis. We observed an increase in the transcription factor, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1), in parallel with ICAM-1, in human retinal endothelial cells treated with tumor necrosis factor-alpha (TNF-α), and identified putative binding sites for NF-κB1 within the ICAM-1 regulatory region. We targeted induced NF-κB1 expression in endothelial cells with small interfering (si)RNA. Knockdown of NF-κB1 significantly decreased cell surface expression of ICAM-1 protein induced by TNF-α but did not reduce constitutive ICAM-1 expression. Consistently, NF-κB1 knockdown significantly reduced leukocyte binding to cell monolayers in the presence of TNF-α but did not impact baseline binding. Findings of this proof-of-concept study indicate that induced transcription of endothelial adhesion molecules might be targeted therapeutically for inflammatory disease in humans. PMID:27293321

  19. Reversing Adhesion: A Triggered Release Self‐Reporting Adhesive

    PubMed Central

    Schenzel, Alexander M.; Klein, Christopher; Rist, Kai; Moszner, Norbert

    2016-01-01

    Here, the development of an adhesive is reported – generated via free radical polymerization – which can be degraded upon thermal impact within minutes. The degradation is based on a stimuli responsive moiety (SRM) that is incorporated into the network. The selected SRM is a hetero Diels‐Alder (HDA) moiety that features three key properties. First, the adhesive can be degraded at relatively low temperatures (≈80 °C), second the degradation occurs very rapidly (less than 3 min), and third, the degradation of the network can readily be analyzed and quantified due to its self‐reporting nature. The new reversible self‐reporting adhesion system is characterized in detail starting from molecular studies of the retro HDA reaction. Moreover, the mechanical properties of the network, as well as the adhesion forces, are investigated in detail and compared to common methacrylate‐based systems, demonstrating a significant decrease in mechanic stability at elevated temperatures. The current study thus represents a significant advance of the current state of the art for debonding on demand adhesives, making the system interesting for several fields of application including dental adhesives. PMID:27812461

  20. Tissue Kidney Injury Molecule-1 Expression in the Prediction of Renal Function for Several Years after Kidney Biopsy

    PubMed Central

    Simic Ogrizovic, Sanja; Basta-Jovanovic, Gordana; Radojevic, Sanja; Pavlovic, Jelena; Kotur Stevuljevic, Jelena; Dopsaj, Violeta; Naumovic, Radomir

    2013-01-01

    Objectives. Retrospective study was designed to examine the importance of tissue kidney injury molecule-1 (KIM-1) expression in predicting kidney function in sixty patients (27 males) aged 34.15 ± 12.23 years with different kidney diseases over three years after kidney biopsy. Materials and Methods. Tissue KIM-1 expression was determined immunohistochemically and KIM-1 staining was scored semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy, and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later. Results. Significantly positive correlations between tissue KIM-1 expression and age (r = 0.313), TIN inflammation (r = 0.456), fibrosis (r = 0.317), and proteinuria at 6 months (r = 0.394) as well as negative correlations with GFR0 (r = −0.572), GFR6 (r = −0.442), GFR24 (r = −0.398), and GFR36 (r = −0.412) were found. Meanwhile, TIN inflammation was the best predictor of all measured kidney functions during three years, while tissue KIM-1 expression (P = 0.016) was a predictor only at 6 months after biopsy. Conclusion. Tissue KIM-1 expression significantly predicts kidney function solely at 6 months after biopsy, when the effects of immune and nonimmune treatments are the strongest. PMID:24282337

  1. Silencing stromal interaction molecule 1 by RNA interference inhibits the proliferation and migration of endothelial progenitor cells

    SciTech Connect

    Kuang, Chun-yan; Yu, Yang; Guo, Rui-wei; Qian, De-hui; Wang, Kui; Den, Meng-yang; Shi, Yan-kun; Huang, Lan

    2010-07-23

    Research highlights: {yields} STIM1 and TRPC1 are expressed in EPCs. {yields} Knockdown of STIM1 inhibits the proliferation, migration and SOCE of EPCs. {yields} TRPC1-SOC cooperates with STIM1 to mediate the SOCE of EPCs. -- Abstract: Knockdown of stromal interaction molecule 1 (STIM1) significantly suppresses neointima hyperplasia after vascular injury. Endothelial progenitor cells (EPCs) are the major source of cells that respond to endothelium repair and contribute to re-endothelialization by reducing neointima formation after vascular injury. We hypothesized that the effect of STIM1 on neointima hyperplasia inhibition is mediated through its effect on the biological properties of EPCs. In this study, we investigated the effects of STIM1 on the proliferation and migration of EPCs and examined the effect of STIM1 knockdown using cultured rat bone marrow-derived EPCs. STIM1 was expressed in EPCs, and knockdown of STIM1 by adenoviral delivery of small interfering RNA (siRNA) significantly suppressed the proliferation and migration of EPCs. Furthermore, STIM1 knockdown decreased store-operated channel entry 48 h after transfection. Replenishment with recombinant human STIM1 reversed the effects of STIM1 knockdown. Our data suggest that the store-operated transient receptor potential canonical 1 channel is involved in regulating the biological properties of EPCs through STIM1. STIM1 is a potent regulator of cell proliferation and migration in rat EPCs and may play an important role in the biological properties of EPCs.

  2. A stromal interaction molecule 1 variant up-regulates matrix metalloproteinase-2 expression by strengthening nucleoplasmic Ca2+ signaling.

    PubMed

    Chen, Fengrong; Zhu, Liping; Cai, Lei; Zhang, Jiwei; Zeng, Xianqin; Li, Jiansha; Su, Yuan; Hu, Qinghua

    2016-04-01

    Very recent studies hold promise to reveal the role of stromal interaction molecule 1 (STIM1) in non-store-operated Ca2+ entry. Here we showed that in contrast to cytoplasmic membrane redistribution as previously noted, human umbilical vein endothelial STIM1 with a T-to-C nucleotide transition resulting in an amino acid substitution of leucine by proline in the signal peptide sequence translocated to perinuclear membrane upon intracellular Ca2+ depletion, amplified nucleoplasmic Ca2+ signaling through ryanodine receptor-dependent pathway, and enhanced the subsequent cAMP responsive element binding protein activity, matrix metalloproteinase-2 (MMP-2) gene expression, and endothelial tube forming. The abundance of mutated STIM1 and the MMP-2 expression were higher in native human umbilical vein endothelial cells of patients with gestational hypertension than controls and were significantly correlated with blood pressure. These findings broaden our understanding about structure-function bias of STIM1 and offer unique insights into its application in nucleoplasmic Ca2+, MMP-2 expression, endothelial dysfunction, and pathophysiological mechanism(s) of gestational hypertension. PMID:26775216

  3. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

    PubMed Central

    Ismail, Ola Z.; Zhang, Xizhong; Wei, Junjun; Haig, Aaron; Denker, Bradley M.; Suri, Rita S.; Sener, Alp; Gunaratnam, Lakshman

    2016-01-01

    Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1+/+ mice, Kim-1−/− mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1–deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12. PMID:25759266

  4. Adhesion in vascular biology

    PubMed Central

    de Rooij, Johan

    2014-01-01

    The vasculature delivers vital support for all other tissues by supplying oxygen and nutrients for growth and by transporting the immune cells that protect and cure them. Therefore, the microvasculature developed a special barrier that is permissive for gasses like oxygen and carbon dioxide, while fluids are kept inside and pathogens are kept out. While maintaining this tight barrier, the vascular wall also allows immune cells to exit at sites of inflammation or damage, a process that is called transmigration. The endothelial cell layer that forms the inner lining of the vasculature is crucial for the vascular barrier function as well as the regulation of transmigration. Therefore, adhesions between vascular endothelial cells are both tight and dynamic and the mechanisms by which they are established, and the mechanisms by which they are controlled have been extensively studied over the past decades. Because of our fundamental strive to understand biology, but also because defects in vascular barrier control cause a variety of clinical problems and treatment strategies may evolve from our detailed understanding of its mechanisms. This special focus issue features a collection of articles that review key components of the development and control of the endothelial cell-cell junction that is central to endothelial barrier function. PMID:25422845

  5. Seafood delicacy makes great adhesive

    ScienceCinema

    Idaho National Laboratory - Frank Roberto, Heather Silverman

    2016-07-12

    Technology from Mother Nature is often hard to beat, so Idaho National Laboratory scientistsgenetically analyzed the adhesive proteins produced by blue mussels, a seafood delicacy. Afterobtaining full-length DNA sequences encoding these proteins, reprod

  6. Seafood delicacy makes great adhesive

    SciTech Connect

    Idaho National Laboratory - Frank Roberto, Heather Silverman

    2008-03-26

    Technology from Mother Nature is often hard to beat, so Idaho National Laboratory scientistsgenetically analyzed the adhesive proteins produced by blue mussels, a seafood delicacy. Afterobtaining full-length DNA sequences encoding these proteins, reprod

  7. Endothelial cells derived from human embryonic stem cells

    NASA Astrophysics Data System (ADS)

    Levenberg, Shulamit; Golub, Justin S.; Amit, Michal; Itskovitz-Eldor, Joseph; Langer, Robert

    2002-04-01

    Human embryonic stem cells have the potential to differentiate into various cell types and, thus, may be useful as a source of cells for transplantation or tissue engineering. We describe here the differentiation steps of human embryonic stem cells into endothelial cells forming vascular-like structures. The human embryonic-derived endothelial cells were isolated by using platelet endothelial cell-adhesion molecule-1 (PECAM1) antibodies, their behavior was characterized in vitro and in vivo, and their potential in tissue engineering was examined. We show that the isolated embryonic PECAM1+ cells, grown in culture, display characteristics similar to vessel endothelium. The cells express endothelial cell markers in a pattern similar to human umbilical vein endothelial cells, their junctions are correctly organized, and they have high metabolism of acetylated low-density lipoprotein. In addition, the cells are able to differentiate and form tube-like structures when cultured on matrigel. In vivo, when transplanted into SCID mice, the cells appeared to form microvessels containing mouse blood cells. With further studies, these cells could provide a source of human endothelial cells that could be beneficial for potential applications such as engineering new blood vessels, endothelial cell transplantation into the heart for myocardial regeneration, and induction of angiogenesis for treatment of regional ischemia.

  8. The effect of shear stress on human endothelial cells seeded on cylindrical viscoelastic conduits: an investigation of gene expression.

    PubMed

    Vara, Dina S; Punshon, Geoffrey; Sales, Kevin M; Hamilton, George; Seifalian, Alexander M

    2006-11-01

    The present study assesses the effect of physiological shear stress on gene expression from human ECs (endothelial cells) seeded on a small-diameter cylindrical bypass graft constructed from nanocomposite based on poly(carbonate-silsesquioxane-bridge-urea)urethane. ECs were seeded on to 5-mm-diameter conduits, placed in a physiological flow circuit and exposed to 1 or 4 h of shear stress at 1.4+/-0.3 Pa. Subsets of conduits were incubated at 37 degrees C and 5% CO2/95% O2 for a further 4 h to determine if gene expression returned to basal levels. PCR was conducted for glyceraldehyde-3-phosphate dehydrogenase, TGFbeta-1 (transforming growth factor beta-1), COL-1 (collagen-1) and PECAM-1 (platelet/EC adhesion molecule-1). Increases in gene expression were seen following flow in nanocomposite conduits. These were significant at 4 h for TGFbeta-1, COL-1 and PECAM-1. After a 4 h recovery period, there were no significant differences in gene intensity, suggesting that this change is transient. These data prove that mRNA can be obtained from ECs seeded on tubular conduits and exposed to shear stress and that gene-expression studies can be successfully carried out. We believe this is a substantial improvement on studies based on flat sheets.

  9. Molecular engineering of high affinity single-chain antibody fragment for endothelial targeting of proteins and nanocarriers in rodents and humans.

    PubMed

    Greineder, Colin F; Hood, Elizabeth D; Yao, Anning; Khoshnejad, Makan; Brenner, Jake S; Johnston, Ian H; Poncz, Mortimer; Gottstein, Claudia; Muzykantov, Vladimir R

    2016-03-28

    Endothelial cells (EC) represent an important target for pharmacologic intervention, given their central role in a wide variety of human pathophysiologic processes. Studies in lab animal species have established that conjugation of drugs and carriers with antibodies directed to surface targets like the Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, a highly expressed endothelial transmembrane protein) help to achieve specific therapeutic interventions in ECs. To translate such "vascular immunotargeting" to clinical practice, it is necessary to replace antibodies by advanced ligands that are more amenable to use in humans. We report the molecular design of a single chain variable antibody fragment (scFv) that binds with high affinity to human PECAM-1 and cross-reacts with its counterpart in rats and other animal species, allowing parallel testing in vivo and in human endothelial cells in microfluidic model. Site-specific modification of the scFv allows conjugation of protein cargo and liposomes, enabling their endothelial targeting in these models. This study provides a template for molecular engineering of ligands, enabling studies of drug targeting in animal species and subsequent use in humans. PMID:26855052

  10. Adhesive interactions between vesicles in the strong adhesion limit

    PubMed Central

    Ramachandran, Arun; Anderson, Travers H.; Leal, L. Gary; Israelachvili, Jacob N.

    2010-01-01

    We consider the adhesive interaction energy between a pair of vesicles in the strong adhesion limit, in which bending forces play a negligible role in determining vesicle shape compared to forces due to membrane stretching. Although force-distance or energy distance relationships characterizing adhesive interactions between fluid bilayers are routinely measured using the surface forces apparatus, the atomic force microscope and the biomembrane force probe, the interacting bilayers in these methods are supported on surfaces (e.g. mica sheet) and cannot be deformed. However, it is known that in a suspension, vesicles composed of the same bilayer can deform by stretching or bending, and can also undergo changes in volume. Adhesively interacting vesicles can thus form flat regions in the contact zone, which will result in an enhanced interaction energy as compared to rigid vesicles. The focus of this paper is to examine the magnitude of the interaction energy between adhesively interacting, deformed vesicles relative to free, undeformed vesicles as a function of the intervesicle separation. The modification of the intervesicle interaction energy due to vesicle deformability can be calculated knowing the undeformed radius of the vesicles, R0, the bending modulus kb, the area expansion modulus Ka, and the adhesive minimum WP(0) and separation DP(0) in the energy of interaction between two flat bilayers, which can be obtained from the force-distance measurements made using the above supported-bilayer methods. For vesicles with constant volumes, we show that adhesive potentials between non-deforming bilayers such as ∣WP(0)∣∼5×10−4mJ/m2, which are ordinarily considered weak in colloidal physics literature, can result in significantly deep (>10×) energy minima due to increase in vesicle area and flattening in the contact region. If the osmotic expulsion of water across the vesicles driven by the tense, stretched membrane in the presence of an osmotically active

  11. Adhesive interactions between vesicles in the strong adhesion limit.

    PubMed

    Ramachandran, Arun; Anderson, Travers H; Leal, L Gary; Israelachvili, Jacob N

    2011-01-01

    We consider the adhesive interaction energy between a pair of vesicles in the strong adhesion limit, in which bending forces play a negligible role in determining vesicle shape compared to forces due to membrane stretching. Although force−distance or energy−distance relationships characterizing adhesive interactions between fluid bilayers are routinely measured using the surface forces apparatus, the atomic force microscope, and the biomembrane force probe, the interacting bilayers in these methods are supported on surfaces (e.g., mica sheet) and cannot be deformed. However, it is known that, in a suspension, vesicles composed of the same bilayer can deform by stretching or bending, and can also undergo changes in volume. Adhesively interacting vesicles can thus form flat regions in the contact zone, which will result in an enhanced interaction energy as compared to rigid vesicles. The focus of this paper is to examine the magnitude of the interaction energy between adhesively interacting, deformed vesicles relative to free, undeformed vesicles as a function of the intervesicle separation. The modification of the intervesicle interaction energy due to vesicle deformability can be calculated knowing the undeformed radius of the vesicles, R0, the bending modulus, k(b), the area expansion modulus, k(a), and the adhesive minimum, W(P)(0), and separation, D(P)(0), in the energy of interaction between two flat bilayers, which can be obtained from the force−distance measurements made using the above supported-bilayer methods. For vesicles with constant volumes, we show that adhesive potentials between nondeforming bilayers such as |W(P)(0)| 5 × 10(−4) mJ/m2, which are ordinarily considered weak in the colloidal physics literature, can result in significantly deep (>10×) energy minima due to increase in vesicle area and flattening in the contact region. If the osmotic expulsion of water across the vesicles driven by the tense, stretched membrane in the presence

  12. Mechanisms of adhesion in geckos.

    PubMed

    Autumn, Kellar; Peattie, Anne M

    2002-12-01

    The extraordinary adhesive capabilities of geckos have challenged explanation for millennia, since Aristotle first recorded his observations. We have discovered many of the secrets of gecko adhesion, yet the millions of dry, adhesive setae on the toes of geckos continue to generate puzzling new questions and valuable answers. Each epidermally-derived, keratinous seta ends in hundreds of 200 nm spatular tips, permitting intimate contact with rough and smooth surfaces alike. Prior studies suggested that adhesive force in gecko setae was directly proportional to the water droplet contact angle (θ) , an indicator of the free surface energy of a substrate. In contrast, new theory suggests that adhesion energy between a gecko seta and a surface (W(GS)) is in fact proportional to (1 + cosθ), and only for θ > 60°. A reanalysis of prior data, in combination with our recent study, support the van der Waals hypothesis of gecko adhesion, and contradict surface hydrophobicity as a predictor of adhesion force. Previously, we and our collaborators measured the force production of a single seta. Initial efforts to attach a seta failed because of improper 3D orientation. However, by simulating the dynamics of gecko limbs during climbing (based on force plate data) we discovered that, in single setae, a small normal preload, combined with a 5 μm displacement yielded a very large adhesive force of 200 microNewton (μN), 10 times that predicted by whole-animal measurements. 6.5 million setae of a single tokay gecko attached maximally could generate 130 kg force. This raises the question of how geckos manage to detach their feet in just 15 ms. We discovered that simply increasing the angle that the setal shaft makes with the substrate to 30° causes detachment. Understanding how simultaneous attachment and release of millions of setae are controlled will require an approach that integrates levels ranging from molecules to lizards.

  13. Silorane adhesive system: a case report.

    PubMed

    Ruschel, Vanessa Carla; Baratieri, Luiz Narciso; Monteiro Júnior, Sylvio; Andrada, Mauro Amaral Caldeira de

    2014-01-01

    Silorane-based composite resin requires a specific adhesive system: a 2-step self-etching adhesive. Clinical protocols are well established and are based on the principles of adhesion to mineralized dental tissues. In this paper, we present a clinical application of the silorane adhesive system in a class-II restoration using silorane-based composite resin.

  14. Fibrillar Adhesive for Climbing Robots

    NASA Technical Reports Server (NTRS)

    Pamess, Aaron; White, Victor E.

    2013-01-01

    A climbing robot needs to use its adhesive patches over and over again as it scales a slope. Replacing the adhesive at each step is generally impractical. If the adhesive or attachment mechanism cannot be used repeatedly, then the robot must carry an extra load of this adhesive to apply a fresh layer with each move. Common failure modes include tearing, contamination by dirt, plastic deformation of fibers, and damage from loading/ unloading. A gecko-like fibrillar adhesive has been developed that has been shown useful for climbing robots, and may later prove useful for grasping, anchoring, and medical applications. The material consists of a hierarchical fibrillar structure that currently contains two levels, but may be extended to three or four levels in continuing work. The contacting level has tens of thousands of microscopic fibers made from a rubberlike material that bend over and create intimate contact with a surface to achieve maximum van der Waals forces. By maximizing the real area of contact that these fibers make and minimizing the bending energy necessary to achieve that contact, the net amount of adhesion has been improved dramatically.

  15. Loss of Reelin protects against atherosclerosis by reducing leukocyte-endothelial cell adhesion and lesion macrophage accumulation.

    PubMed

    Ding, Yinyuan; Huang, Linzhang; Xian, Xunde; Yuhanna, Ivan S; Wasser, Catherine R; Frotscher, Michael; Mineo, Chieko; Shaul, Philip W; Herz, Joachim

    2016-03-15

    The multimodular glycoprotein Reelin controls neuronal migration and synaptic transmission by binding to apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr) on neurons. In the periphery, Reelin is produced by the liver, circulates in blood, and promotes thrombosis and hemostasis. To investigate if Reelin influences atherogenesis, we studied atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice in which we inducibly deleted Reelin either ubiquitously or only in the liver, thus preventing the production of circulating Reelin. In both types of Reelin-deficient mice, atherosclerosis progression was markedly attenuated, and macrophage content and endothelial cell staining for vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were reduced at the sites of atherosclerotic lesions. Intravital microscopy revealed decreased leukocyte-endothelial adhesion in the Reelin-deficient mice. In cultured human endothelial cells, Reelin enhanced monocyte adhesion and increased ICAM1, VCAM1, and E-selectin expression by suppressing endothelial nitric oxide synthase (eNOS) activity and increasing nuclear factor κB (NF-κB) activity in an Apoer2-dependent manner. These findings suggest that circulating Reelin promotes atherosclerosis by increasing vascular inflammation, and that reducing or inhibiting circulating Reelin may present a novel approach for the prevention of cardiovascular disease.

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

    PubMed Central

    O'Brien, Kylie A.; Ling, Shanhong; Abbas, Estelle; Dai, Aozhi; Zhang, Jiansheng; Wang, Wen Cheng; Bensoussan, Alan; Luo, Ruizhi; Guo, Zhi-Xin; Komesaroff, Paul A.

    2011-01-01

    Circulating adhesion molecules (CAMs), surface proteins expressed in the vascular endothelium, have emerged as risk factors for cardiovascular disease (CVD). CAMs are involved in intercellular communication that are believed to play a role in atherosclerosis. A Chinese medicine, the “Dantonic Pill” (DP) (also known as the “Cardiotonic Pill”), containing three Chinese herbal material medica, Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum, has been used in China for the prevention and management of CVD. Previous laboratory and animal studies have suggested that this preparation reduces both atherogenesis and adhesion molecule expression. A parallel double blind randomized placebo-controlled study was conducted to assess the effects of the DP on three species of CAM (intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 and endothelial cell selectin (E-selectin)) in participants with mild-moderate hypercholesterolemia. Secondary endpoints included biochemical and hematological variables and clinical effects. Forty participants were randomized to either treatment or control for 12 weeks. Treatment with DP was associated with a statistically significant decrease in ICAM-1 (9% decrease, P = .03) and E-Selectin (15% decrease, P = .004). There was no significant change in renal function tests, liver function tests, glucose, lipids or C-reactive protein levels and clinical adverse effects did not differ between the active and the control groups. There were no relevant changes in participants receiving placebo. These results suggest that this herbal medicine may contribute to the development of a novel approach to cardiovascular risk reduction. PMID:18955365

  17. Focal adhesion kinase

    PubMed Central

    Stone, Rebecca L; Baggerly, Keith A; Armaiz-Pena, Guillermo N; Kang, Yu; Sanguino, Angela M; Thanapprapasr, Duangmani; Dalton, Heather J; Bottsford-Miller, Justin; Zand, Behrouz; Akbani, Rehan; Diao, Lixia; Nick, Alpa M; DeGeest, Koen; Lopez-Berestein, Gabriel; Coleman, Robert L; Lutgendorf, Susan; Sood, Anil K

    2014-01-01

    This investigation describes the clinical significance of phosphorylated focal adhesion kinase (FAK) at the major activating tyrosine site (Y397) in epithelial ovarian cancer (EOC) cells and tumor-associated endothelial cells. FAK gene amplification as a mechanism for FAK overexpression and the effects of FAK tyrosine kinase inhibitor VS-6062 on tumor growth, metastasis, and angiogenesis were examined. FAK and phospho-FAKY397 were quantified in tumor (FAK-T; pFAK-T) and tumor-associated endothelial (FAK-endo; pFAK-endo) cell compartments of EOCs using immunostaining and qRT-PCR. Associations between expression levels and clinical variables were evaluated. Data from The Cancer Genome Atlas were used to correlate FAK gene copy number and expression levels in EOC specimens. The in vitro and in vivo effects of VS-6062 were assayed in preclinical models. FAK-T and pFAK-T overexpression was significantly associated with advanced stage disease and increased microvessel density (MVD). High MVD was observed in tumors with elevated endothelial cell FAK (59%) and pFAK (44%). Survival was adversely affected by FAK-T overexpression (3.03 vs 2.06 y, P = 0.004), pFAK-T (2.83 vs 1.78 y, P < 0.001), and pFAK-endo (2.33 vs 2.17 y, P = 0.005). FAK gene copy number was increased in 34% of tumors and correlated with expression levels (P < 0.001). VS-6062 significantly blocked EOC and endothelial cell migration as well as endothelial cell tube formation in vitro. VS-6062 reduced mean tumor weight by 56% (P = 0.005), tumor MVD by 40% (P = 0.0001), and extraovarian metastasis (P < 0.01) in orthotopic EOC mouse models. FAK may be a unique therapeutic target in EOC given the dual anti-angiogenic and anti-metastatic potential of FAK inhibitors. PMID:24755674

  18. Investigation of organic adhesives for hybrid microcircuits

    NASA Technical Reports Server (NTRS)

    Perkins, K. L.; Licari, J. J.

    1975-01-01

    The properties of organic adhesives were investigated to acquire information for a guideline document regarding the selection of adhesives for use in high reliability hybrid microcircuits. Specifically, investigations were made of (1) alternate methods for determining the outgassing of cured adhesives, (2) effects of long term aging at 150 C on the electrical properties of conductive adhesives, (3) effects of shelf life age on adhesive characteristics, (4) bond strengths of electrically conductive adhesives on thick film gold metallization, (5) a copper filled adhesive, (6) effects of products outgassed from cured adhesives on device electrical parameters, (7) metal migration from electrically conductive adhesives, and (8) ionic content of electrically insulative adhesives. The tests performed during these investigations are described, and the results obtained are discussed.

  19. Increased plasma Kidney Injury Molecule-1 suggests early progressive renal decline in non-proteinuric patients with Type 1 diabetes

    PubMed Central

    Nowak, Natalia; Skupien, Jan; Niewczas, Monika A.; Yamanouchi, Masayuki; Major, Melissa; Croall, Stephanie; Smiles, Adam; Warram, James H.; Bonventre, Joseph V.; Krolewski, Andrzej S.

    2015-01-01

    Progressively decreasing glomerular filtration rate (GFR), or renal decline, is seen in patients with type 1 diabetes (T1D) and normoalbuminuria or microalbuminuria. Here we examined the associations of kidney injury molecule-1 (KIM-1) in plasma and urine with the risk of renal decline and determine whether those associations are independent of markers of glomerular damage. The study group comprised patients with T1D from the 2nd Joslin Kidney Study of which 259 had normoalbuminuria and 203 had microalbuminuria. Serial measurements over 4 to 10 years of follow-up (median 8 years) of serum creatinine and cystatin C were used jointly to estimate eGFRcr-cys slopes and time of onset of CKD stage 3 or higher. Baseline urinary excretion of IgG2 and albumin were used as markers of glomerular damage, and urinary excretion of KIM-1 and its plasma concentration were used as markers of proximal tubular damage. All patients had normal renal function at baseline. During follow-up, renal decline (eGFRcr-cys loss 3.3% or more per year) developed in 96 patients and 62 progressed to CKD stage 3. For both outcomes, the risk rose with increasing baseline levels of plasma KIM-1. In multivariable models, elevated baseline plasma KIM-1 was strongly associated with risk of early progressive renal decline, regardless of baseline clinical characteristics, serum TNFR1 or markers of glomerular damage. Thus, damage to proximal tubules may play an independent role in the development of early progressive renal decline in non-proteinuric patients with T1D. PMID:26509588

  20. Plasma polymerization for cell adhesive/anti-adhesive implant coating

    NASA Astrophysics Data System (ADS)

    Meichsner, Juergen; Testrich, Holger; Rebl, Henrike; Nebe, Barbara

    2015-09-01

    Plasma polymerization of ethylenediamine (C2H8N2, EDA) and perfluoropropane (C3F8, PFP) with admixture of argon and hydrogen, respectively, was studied using an asymmetric 13.56 MHz CCP. The analysis of the plasma chemical gas phase processes for stable molecules revealed consecutive reactions: C2H8N2 consumption, intermediate product NH3, and main final product HCN. In C3F8- H2 plasma the precursor molecule C3F8 and molecular hydrogen are consumed and HF as well as CF4 and C2F6 are found as main gaseous reaction products. The deposited plasma polymer films on the powered electrode are strongly cross-linked due to ion bombardment. The stable plasma polymerized films from EDA are characterized by high content of nitrogen with N/C ratio of about 0.35. The plasma polymerized fluorocarbon film exhibit a reduced F/C ratio of about 1.2. Adhesion tests with human osteoblast cell line MG-63 on coated Ti6Al4V samples (polished) compared with uncoated reference sample yielded both, the enhanced cell adhesion for plasma polymerized EDA and significantly reduced cell adhesion for fluorocarbon coating, respectively. Aging of the plasma polymerized EDA film, in particular due to the reactions with oxygen from air, showed no significant change in the cell adhesion. The fluorocarbon coating with low cell adhesion is of interest for temporary implants. Funded by the Campus PlasmaMed.

  1. Optimizing Adhesive Design by Understanding Compliance.

    PubMed

    King, Daniel R; Crosby, Alfred J

    2015-12-23

    Adhesives have long been designed around a trade-off between adhesive strength and releasability. Geckos are of interest because they are the largest organisms which are able to climb utilizing adhesive toepads, yet can controllably release from surfaces and perform this action over and over again. Attempting to replicate the hierarchical, nanoscopic features which cover their toepads has been the primary focus of the adhesives field until recently. A new approach based on a scaling relation which states that reversible adhesive force capacity scales with (A/C)(1/2), where A is the area of contact and C is the compliance of the adhesive, has enabled the creation of high strength, reversible adhesives without requiring high aspect ratio, fibrillar features. Here we introduce an equation to calculate the compliance of adhesives, and utilize this equation to predict the shear adhesive force capacity of the adhesive based on the material components and geometric properties. Using this equation, we have investigated important geometric parameters which control force capacity and have shown that by controlling adhesive shape, adhesive force capacity can be increased by over 50% without varying pad size. Furthermore, we have demonstrated that compliance of the adhesive far from the interface still influences shear adhesive force capacity. Utilizing this equation will allow for the production of adhesives which are optimized for specific applications in commercial and industrial settings. PMID:26618537

  2. Optimizing Adhesive Design by Understanding Compliance.

    PubMed

    King, Daniel R; Crosby, Alfred J

    2015-12-23

    Adhesives have long been designed around a trade-off between adhesive strength and releasability. Geckos are of interest because they are the largest organisms which are able to climb utilizing adhesive toepads, yet can controllably release from surfaces and perform this action over and over again. Attempting to replicate the hierarchical, nanoscopic features which cover their toepads has been the primary focus of the adhesives field until recently. A new approach based on a scaling relation which states that reversible adhesive force capacity scales with (A/C)(1/2), where A is the area of contact and C is the compliance of the adhesive, has enabled the creation of high strength, reversible adhesives without requiring high aspect ratio, fibrillar features. Here we introduce an equation to calculate the compliance of adhesives, and utilize this equation to predict the shear adhesive force capacity of the adhesive based on the material components and geometric properties. Using this equation, we have investigated important geometric parameters which control force capacity and have shown that by controlling adhesive shape, adhesive force capacity can be increased by over 50% without varying pad size. Furthermore, we have demonstrated that compliance of the adhesive far from the interface still influences shear adhesive force capacity. Utilizing this equation will allow for the production of adhesives which are optimized for specific applications in commercial and industrial settings.

  3. Innovative Electrostatic Adhesion Technologies

    NASA Astrophysics Data System (ADS)

    Gagliano, L.; Bryan, T.; Williams, S.; McCoy, B.; MacLeod, T.

    Developing specialized Electro-Static grippers (commercially used in Semiconductor Manufacturing and in package handling) will allow gentle and secure Capture, Soft Docking, and Handling of a wide variety of materials and shapes (such as upper-stages, satellites, arrays, and possibly asteroids) without requiring physical features or cavities for a pincher or probe or using harpoons or nets. Combined with new rigid boom mechanisms or small agile chaser vehicles, flexible, high speed Electro-Static Grippers can enable compliant capture of spinning objects starting from a safe stand-off distance. Electroadhesion (EA) can enable lightweight, ultra-low-power, compliant attachment in space by using an electrostatic force to adhere similar and dissimilar surfaces. A typical EA enabled device is composed of compliant space-rated materials, such as copper-clad polyimide encapsulated by polymers. Attachment is induced by strong electrostatic forces between any substrate material, such as an exterior satellite panel and a compliant EA surface. When alternate positive and negative charges are induced in adjacent planar electrodes in an EA surface, the electric fields set up opposite charges on the substrate and cause an electrostatic adhesion between the electrodes and the induced charges on the substrate. Since the electrodes and the polymer are compliant and can conform to uneven or rough surfaces, the electrodes can remain intimately close to the entire surface, enabling high clamping pressures. Clamping pressures of more than 3 N/cm2 in shear can be achieved on a variety of substrates with ultra-low holding power consumption (measured values are less than 20 microW/Newton weight held). A single EA surface geometry can be used to clamp both dielectric and conductive substrates, with slightly different physical mechanisms. Furthermore EA clamping requires no normal force be placed on the substrate, as conventional docking requires. Internally funded research and development

  4. Innovative Electrostatic Adhesion Technologies

    NASA Technical Reports Server (NTRS)

    Bryan, Tom; Macleod, Todd; Gagliano, Larry; Williams, Scott; McCoy, Brian

    2015-01-01

    Developing specialized Electro-Static grippers (commercially used in Semiconductor Manufacturing and in package handling) will allow gentle and secure Capture, Soft Docking, and Handling of a wide variety of materials and shapes (such as upper-stages, satellites, arrays, and possibly asteroids) without requiring physical features or cavities for a pincher or probe or using harpoons or nets. Combined with new rigid boom mechanisms or small agile chaser vehicles, flexible, high speed Electro-Static Grippers can enable compliant capture of spinning objects starting from a safe stand-off distance. Electroadhesion (EA) can enable lightweight, ultra-low-power, compliant attachment in space by using an electrostatic force to adhere similar and dissimilar surfaces. A typical EA enabled device is composed of compliant space-rated materials, such as copper-clad polyimide encapsulated by polymers. Attachment is induced by strong electrostatic forces between any substrate material, such as an exterior satellite panel and a compliant EA gripper pad surface. When alternate positive and negative charges are induced in adjacent planar electrodes in an EA surface, the electric fields set up opposite charges on the substrate and cause an electrostatic adhesion between the electrodes and the induced charges on the substrate. Since the electrodes and the polymer are compliant and can conform to uneven or rough surfaces, the electrodes can remain intimately close to the entire surface, enabling high clamping pressures. Clamping pressures of more than 3 N/cm2 in shear can be achieved on a variety of substrates with ultra-low holding power consumption (measured values are less than 20 microW/Newton weight held). A single EA surface geometry can be used to clamp both dielectric and conductive substrates, with slightly different physical mechanisms. Furthermore EA clamping requires no normal force be placed on the substrate, as conventional docking requires. Internally funded research and

  5. Elastocapilllarity in insect adhesion: the case of beetle adhesive hair

    NASA Astrophysics Data System (ADS)

    Gernay, Sophie; Gilet, Tristan; Lambert, Pierre; Federle, Walter

    2014-11-01

    The feet of many insects are covered with dense arrays of hair-like structures called setae. Liquid capillary bridges at the tip of these micrometric structures are responsible for the controlled adhesion of the insect on a large variety of substrates. The resulting adhesion force can exceed several times the body weight of the insect. The high aspect-ratio of setae suggests that flexibility is a key ingredient in this capillary-based adhesion mechanism. There is indeed a strong coupling between their elastic deformation and the shape of the liquid meniscus. In this experimental work, we observe and quantify the local deflection of dock beetle seta tips under perpendicular loading using interference microscopy. Our results are then interpreted in the light of an analytic model of elastocapillarity. This research has been funded by the FRIA/FNRS and the Interuniversity Attraction Poles Programme (IAP 7/38 MicroMAST) initiated by the Belgian Science Policy Office.

  6. Characterization of the inflammatory infiltrate and expression of endothelial cell adhesion molecules in lupus erythematosus tumidus.

    PubMed

    Kuhn, Annegret; Sonntag, Monika; Lehmann, Percy; Megahed, Mosaad; Vestweber, Dietmar; Ruzicka, Thomas

    2002-03-01

    Lupus erythematosus tumidus (LET) is a disease with characteristic clinical and histopathologic features that has not always been considered a subset of cutaneous lupus erythematosus (CLE). Although LET was first mentioned in the literature in 1930, it has rarely been documented, and immunohistochemical studies have never been performed. The aim of the present study was to characterize the inflammatory infiltrate and to analyze the expression of endothelial cell adhesion molecules in skin specimens from patients with LET and to compare the results with those from patients with other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Cryostat sections of lesional skin specimens from ten patients with LET demonstrated an infiltrate composed of more than 75% CD4+, CD8+, and HLA-DR+ cells. Interestingly, CD45RO+ cells, in contrast to CD45RA+ cells, were the prevailing inflammatory cell population. Compared with skin specimens from patients with DLE and SCLE, the mean expression of CD4+ and CD8+ cells was higher (but not significantly so) in LET, and no differences were observed with the other three antibodies. Furthermore, in contrast to controls, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and P-selectin showed the same expression pattern in skin specimens from patients with DLE, SCLE, and LET. In conclusion, the inflammatory infiltrate of LET primarily consists of CD4+/CD8+ lymphocytes. Furthermore, expression of endothelial cell adhesion molecules was equally upregulated in LET compared with the expression in DLE and SCLE, suggesting a similar immunopathomechanism of these subtypes of CLE. PMID:12071156

  7. Capillarity-based switchable adhesion.

    PubMed

    Vogel, Michael J; Steen, Paul H

    2010-02-23

    Drawing inspiration from the adhesion abilities of a leaf beetle found in nature, we have engineered a switchable adhesion device. The device combines two concepts: The surface tension force from a large number of small liquid bridges can be significant (capillarity-based adhesion) and these contacts can be quickly made or broken with electronic control (switchable). The device grabs or releases a substrate in a fraction of a second via a low-voltage pulse that drives electroosmotic flow. Energy consumption is minimal because both the grabbed and released states are stable equilibria that persist with no energy added to the system. Notably, the device maintains the integrity of an array of hundreds to thousands of distinct interfaces during active reconfiguration from droplets to bridges and back, despite the natural tendency of the liquid toward coalescence. We demonstrate the scaling of adhesion strength with the inverse of liquid contact size. This suggests that strengths approaching those of permanent bonding adhesives are possible as feature size is scaled down. In addition, controllability is fast and efficient because the attachment time and required voltage also scale down favorably. The device features compact size, no solid moving parts, and is made of common materials.

  8. Capillarity-based switchable adhesion

    PubMed Central

    Vogel, Michael J.; Steen, Paul H.

    2010-01-01

    Drawing inspiration from the adhesion abilities of a leaf beetle found in nature, we have engineered a switchable adhesion device. The device combines two concepts: The surface tension force from a large number of small liquid bridges can be significant (capillarity-based adhesion) and these contacts can be quickly made or broken with electronic control (switchable). The device grabs or releases a substrate in a fraction of a second via a low-voltage pulse that drives electroosmotic flow. Energy consumption is minimal because both the grabbed and released states are stable equilibria that persist with no energy added to the system. Notably, the device maintains the integrity of an array of hundreds to thousands of distinct interfaces during active reconfiguration from droplets to bridges and back, despite the natural tendency of the liquid toward coalescence. We demonstrate the scaling of adhesion strength with the inverse of liquid contact size. This suggests that strengths approaching those of permanent bonding adhesives are possible as feature size is scaled down. In addition, controllability is fast and efficient because the attachment time and required voltage also scale down favorably. The device features compact size, no solid moving parts, and is made of common materials. PMID:20133725

  9. High performance Cu adhesion coating

    SciTech Connect

    Lee, K.W.; Viehbeck, A.; Chen, W.R.; Ree, M.

    1996-12-31

    Poly(arylene ether benzimidazole) (PAEBI) is a high performance thermoplastic polymer with imidazole functional groups forming the polymer backbone structure. It is proposed that upon coating PAEBI onto a copper surface the imidazole groups of PAEBI form a bond with or chelate to the copper surface resulting in strong adhesion between the copper and polymer. Adhesion of PAEBI to other polymers such as poly(biphenyl dianhydride-p-phenylene diamine) (BPDA-PDA) polyimide is also quite good and stable. The resulting locus of failure as studied by XPS and IR indicates that PAEBI gives strong cohesive adhesion to copper. Due to its good adhesion and mechanical properties, PAEBI can be used in fabricating thin film semiconductor packages such as multichip module dielectric (MCM-D) structures. In these applications, a thin PAEBI coating is applied directly to a wiring layer for enhancing adhesion to both the copper wiring and the polymer dielectric surface. In addition, a thin layer of PAEBI can also function as a protection layer for the copper wiring, eliminating the need for Cr or Ni barrier metallurgies and thus significantly reducing the number of process steps.

  10. Induction of heme oxygenase 1 by arsenite inhibits cytokine-induced monocyte adhesion to human endothelial cells

    SciTech Connect

    Sun Xi; Pi Jingbo; Liu Wenlan; Hudson, Laurie G.; Liu Kejian; Feng Changjian

    2009-04-15

    Heme oxygenase-1 (HO-1) is an oxidative stress responsive gene upregulated by various physiological and exogenous stimuli. Arsenite, as an oxidative stressor, is a potent inducer of HO-1 in human and rodent cells. In this study, we investigated the mechanistic role of arsenite-induced HO-1 in modulating tumor necrosis factor {alpha} (TNF-{alpha}) induced monocyte adhesion to human umbilical vein endothelial cells (HUVEC). Arsenite pretreatment, which upregulated HO-1 in a time- and concentration-dependent manner, inhibited TNF-{alpha}-induced monocyte adhesion to HUVEC and intercellular adhesion molecule 1 protein expression by 50% and 40%, respectively. Importantly, knockdown of HO-1 by small interfering RNA abolished the arsenite-induced inhibitory effects. These results indicate that induction of HO-1 by arsenite inhibits the cytokine-induced monocyte adhesion to HUVEC by suppressing adhesion molecule expression. These findings established an important mechanistic link between the functional monocyte adhesion properties of HUVEC and the induction of HO-1 by arsenite.

  11. Modulation of Sickle Red Blood Cell Adhesion and its Associated Changes in Biomarkers by Sulfated Nonanticoagulant Heparin Derivative.

    PubMed

    Alshaiban, Abdulelah; Muralidharan-Chari, Vandhana; Nepo, Anne; Mousa, Shaker A

    2016-04-01

    Abnormal cellular adhesion is one of the primary causes of vaso-occlusive crisis in sickle cell disease (SCD). Levels of intercellular adhesion molecule 1 (ICAM-1) and P-selectin are upregulated, resulting in increased adhesion of leukocytes and sickle red blood cells (RBCs) to endothelium. This study compares the inhibitory effect of a sulfated nonanticoagulant heparin (S-NACH) derivative with a low-molecular-weight heparin, tinzaparin, on the adhesion of sickle RBCs to endothelium. The S-NACH exhibits minimum effects on hemostasis and bleeding and interferes with the binding of pancreatic cancer cells to endothelial cells via P-selectin. We show by static binding assay that pretreatment of both erythrocytes and endothelial cells with S-NACH significantly inhibits the increased adhesion of sickle RBCs to endothelial cells. The S-NACH treatment also decreases the higher plasma levels of (adhesion biomarkers) ICAM-1 and P-selectin in SCD mice. This investigation signals further research into the potential use of S-NACH in treating vaso-occlusions with minimal bleeding events in patients with SCD.

  12. Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion

    SciTech Connect

    Cheng, Huiwen; Mollica, Molly Y.; Lee, Shin Hee; Wang, Lei; Velázquez-Martínez, Carlos A.; Wu, Shiyong

    2012-10-15

    A new class of nitric oxide (NO•)-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) were developed in recent years and have shown promising potential as NSAID substitutes due to their gentle nature on cardiovascular and gastrointestinal systems. Since nitric oxide plays a role in regulation of cell adhesion, we assessed the potential use of NONO-NSAIDs as anti-metastasis drugs. In this regard, we compared the effects of NONO-aspirin and a novel NONO-naproxen to those exerted by their respective parent NSAIDs on avidities of human melanoma M624 cells. Both NONO-NSAIDs, but not the corresponding parent NSAIDs, reduced M624 adhesion on vascular cellular adhesion molecule-1 (VCAM-1) by 20–30% and fibronectin by 25–44% under fluid flow conditions and static conditions, respectively. Only NONO-naproxen reduced (∼ 56%) the activity of β1 integrin, which binds to α4 integrin to form very late antigen-4 (VLA-4), the ligand of VCAM-1. These results indicate that the diazeniumdiolate (NO•)-donor moiety is critical for reducing the adhesion between VLA-4 and its ligands, while the NSAID moiety can impact the regulation mechanism of melanoma cell adhesion. -- Highlights: ► NONO-naproxen, a novel nitric oxide-releasing NSAID, was synthesized. ► NONO-NSAIDs, but not their parent NSAIDs, reduced melanoma adhesion. ► NONO-naproxen, but not NONO-aspirin and NSAIDs, reduced activity of β1 integrin.

  13. Interfacial adhesion: Theory and experiment

    NASA Technical Reports Server (NTRS)

    Ferrante, John; Bozzolo, Guillermo H.; Finley, Clarence W.; Banerjea, Amitava

    1988-01-01

    Adhesion, the binding of different materials at an interface, is of general interest to many branches of technology, e.g., microelectronics, tribology, manufacturing, construction, etc. However, there is a lack of fundamental understanding of such diverse interfaces. In addition, experimental techniques generally have practical objectives, such as the achievement of sufficient strength to sustain mechanical or thermal effects and/or have the proper electronic properties. In addition, the theoretical description of binding at interfaces is quite limited, and a proper data base for such theoretical analysis does not exist. This presentation will review both experimental and theoretical aspects of adhesion in nonpolymer materials. The objective will be to delineate the critical parameters needed, governing adhesion testing along with an outline of testing objectives. A distinction will be made between practical and fundamental objectives. Examples are given where interfacial bonding may govern experimental consideration. The present status of theory is presented along wiith recommendations for future progress and needs.

  14. Interfacial adhesion - Theory and experiment

    NASA Technical Reports Server (NTRS)

    Ferrante, John; Banerjea, Amitava; Bozzolo, Guillermo H.; Finley, Clarence W.

    1988-01-01

    Adhesion, the binding of different materials at an interface, is of general interest to many branches of technology, e.g., microelectronics, tribology, manufacturing, construction, etc. However, there is a lack of fundamental understanding of such diverse interfaces. In addition, experimental techniques generally have practical objectives, such as the achievement of sufficient strength to sustain mechanical or thermal effects and/or have the proper electronic properties. In addition, the theoretical description of binding at interfaces is quite limited, and a proper data base for such theoretical analysis does not exist. This presentation will review both experimental and theoretical aspects of adhesion in nonpolymer materials. The objective will be to delineate the critical parameters needed, governing adhesion testing along with an outline of testing objectives. A distinction will be made between practical and fundamental objectives. Examples are given where interfacial bonding may govern experimental consideration. The present status of theory is presented along with recommendations for future progress and needs.

  15. Platelet adhesiveness after blood donation.

    PubMed

    Pegrum, G D; Harrison, K M; Shaw, S

    1971-03-13

    Platelet adhesiveness to glass was measured in healthy blood donors at the time of and eight days after donating 500 ml of blood. By a whole blood method a highly significant increase was found whereas by a method using platelet-rich plasma with added adenosine diphosphate there was only a slightly significant increase. The discrepancy suggested that changes in the red cell population might influence the results. Packed red cells from 19 blood donors obtained at the time of donation and eight days later were mixed with fresh pooled platelets from the same independent persons on each occasion. The whole blood platelet adhesiveness on this mixture showed an increase in every case after blood donation. It is postulated that the increased adhesiveness is influenced by the presence of young red cells.

  16. UV curable pressure sensitive adhesives

    SciTech Connect

    Glotfelter, C.A.

    1995-12-01

    Pressure sensitive adhesives (PSA`s) have become a ubiquitous element in our society, so much so, that the relative status of a society can be determined by the per capita consumption of PSA`s. We discuss new monomers as components of PSA formulations which enable adhesion to be achieved on a variety of substrates. Since solventless coating systems are desirable, the UV PSA market is of utmost importance to meeting the strict environmental guidelines now being imposed worldwide. In addition, highly ethoxylated monomers have shown promise in water dispersed PSA formulations, and a self-emulsifying acrylate monomer has been developed to offer dispersive abilities without using traditional emulsifying agents. This talk will focus on the effects of the materials described on properties of adhesive strength and shear strength in UV PSA formulations.

  17. Adhesive capsulitis: a case report

    PubMed Central

    Kazemi, Mohsen

    2000-01-01

    Adhesive capsulitis or frozen shoulder is an uncommon entity in athletes. However, it is a common cause of shoulder pain and disability in the general population. Although it is a self limiting ailment, its rather long, restrictive and painful course forces the affected person to seek treatment. Conservative management remains the mainstay treatment of adhesive capsulitis. This includes chiropractic manipulation of the shoulder, therapeutic modalities, mobilization, exercise, soft tissue therapy, nonsteroidal anti-inflammatory drugs, and steroid injections. Manipulation under anesthesia is advocated when the conservative treatment fails. A case of secondary adhesive capsulitis in a forty-seven-year-old female recreational squash player is presented to illustrate clinical presentation, diagnosis, radiographic assessment and conservative chiropractic management. The patient’s shoulder range of motion was full and pain free with four months of conservative chiropractic care. ImagesFigure 1Figure 2Figure 3

  18. A novel addition polyimide adhesive

    NASA Technical Reports Server (NTRS)

    St.clair, T. L.; Progar, D. J.

    1981-01-01

    An addition polyimide adhesive, LARC 13, was developed which shows promise for bonding both titanium and composites for applications which require service temperatures in excess of 533 K. The LARC 13 is based on an oligomeric bis nadimide containing a meta linked aromatic diamine. The adhesive melts prior to polymerization due to its oligomeric nature, thereby allowing it to be processed at 344 kPa or less. Therefore, LARC 13 is ideal for the bonding of honeycomb sandwich structures. After melting, the resin thermosets during the cure of the nadic endcaps to a highly crosslinked system. Few volatiles are evolved, thus allowing large enclosed structures to be bonded. Preparation of the adhesive as well as bonding, aging, and testing of lap shear and honeycomb samples are discussed.

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

    SciTech Connect

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

    2009-10-15

    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.

  20. Adhesive, elastomeric gel impregnating composition

    DOEpatents

    Shaw, David Glenn; Pollard, John Randolph; Brooks, Robert Aubrey

    2002-01-01

    An improved capacitor roll with alternating film and foil layers is impregnated with an adhesive, elastomeric gel composition. The gel composition is a blend of a plasticizer, a polyol, a maleic anhydride that reacts with the polyol to form a polyester, and a catalyst for the reaction. The impregnant composition is introduced to the film and foil layers while still in a liquid form and then pressure is applied to aid with impregnation. The impregnant composition is cured to form the adhesive, elastomeric gel. Pressure is maintained during curing.

  1. Dual-Mode Adhesive Pad

    NASA Technical Reports Server (NTRS)

    Hartz, Leslie

    1994-01-01

    Tool helps worker grip and move along large, smooth structure with no handgrips or footholds. Adheres to surface but easily released by actuating simple mechanism. Includes handle and segmented contact-adhesive pad. Bulk of pad made of soft plastic foam conforming to surface of structure. Each segment reinforced with rib. In sticking mode, ribs braced by side catches. In peeling mode, side catches retracted, and segmented adhesive pad loses its stiffness. Modified versions useful in inspecting hulls of ships and scaling walls in rescue operations.

  2. Protein adhesion force dynamics and single adhesion events.

    PubMed Central

    Sagvolden, G

    1999-01-01

    Using the manipulation force microscope, a novel atomic force microscope, the adhesion forces of bovine serum albumin, myoglobin, ferritin, and lysozyme proteins to glass and polystyrene substrates were characterized by following the force necessary to displace an adsorbed protein-covered microsphere over several orders of magnitude in time. This force was consistent with a power law with exponent a = 0.37 +/- 0.03 on polystyrene, indicating that there is no typical time scale for adhesion on this substrate. On glass, the rate of adhesion depended strongly on protein charge. Forces corresponding to single protein adhesion events were identified. The typical rupture force of a single lysozyme, ferritin, bovine serum albumin, and myoglobin protein adhering to glass was estimated to be 90 +/- 10 pN, 115 +/- 13 pN, 277 +/- 44 pN, and 277 +/- 44 pN, respectively, using a model of the experimental system. These forces, as well as the force amplitudes on hydrophobic polystyrene, correlate with protein stiffness. PMID:10388777

  3. [FTIR spectroscopic studies of facial prosthetic adhesives].

    PubMed

    Kang, Biao; Yang, Qing-fang; Liang, Jian-feng; Zhao, Yi-min

    2008-10-01

    According to the composition of the traditional facial prosthetic adhesives, most of adhesives can be classified into two categories: acrylic polymer-based adhesive and silicone-based adhesive. In previous studies, measurements of various mechanical bond strengths were carried out, whereas the functional groups of the adhesives were evaluated seldom during the adhesion. In the present study the analysis of two facial prosthetic adhesives (Epithane and Secure Adhesive) was carried out by using infrared spectroscopy. Two adhesives in the form of fluid or semisolid were submitted to FTIR spectroscopy, respectively. The results showed that water and ammonia residue volatilized during the solidification of Epithane, and absorption peak reduction of carbonyl was due to the volatilization of acetate vinyl from Secure Adhesive. Similar silicone functional groups both in the silicone-based adhesive and in silicone elastomer could be the key to higher bond strength between silicone elastomer and skin with silicone-based adhesive. The position, shape of main absorption peaks of three adhesives didn't change, which showing that their main chemicals and basic structures didn't change during solidification. PMID:19123392

  4. Dietary fish oil diminishes lymphocyte adhesion to macrophage and endothelial cell monolayers.

    PubMed Central

    Sanderson, P; Calder, P C

    1998-01-01

    To further investigate the immunomodulatory effects of dietary lipids, rats were fed on a low-fat diet or on high-fat diets that contained hydrogenated coconut, olive, safflower, evening primrose or fish oil as the principal fat source. The fish oil diet decreased the level of expression of CD2, CD11a, CD18 and CD44 on the surface of freshly prepared lymphocytes and of CD2, CD11a, CD18, CD54 (intercellular adhesion molecule-1; ICAM-1) and CD62L (L-selectin) on the surface of concanavalin A (Con A)-stimulated lymphocytes. The olive oil diet also resulted in decreased expression of some adhesion molecules. The fish or olive oil diets, and to a lesser extent the safflower or evening primrose oil diets, decreased the adhesion of both freshly prepared and Con A-stimulated lymphocytes to macrophage monolayers. The fish oil diet, and to a lesser extent the olive or evening primrose oil diets, reduced the ability of Con A-stimulated lymphocytes to adhere to untreated endothelial cells. Furthermore, the fish oil diet resulted in a 50% reduction in Con A-stimulated lymphocyte adhesion to tumour necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. This study demonstrates that dietary lipids affect the expression of functionally important adhesion molecules on the surface of lymphocytes. Furthermore, this study suggests that such diet-induced effects on adhesion molecule expression might alter the ability of lymphocytes to bind to macrophages and to endothelial cells. Of the diets studied fish oil causes the most significant effects. The results of this study suggest that a reduction in cellular infiltration may partly explain the protective effect of a fish-oil-rich diet against the development of inflammatory and cardiovascular diseases. PMID:9708190

  5. New adhesive withstands temperature extremes

    NASA Technical Reports Server (NTRS)

    Park, J. J.; Seidenberg, B.

    1978-01-01

    Adhesive, developed for high-temperature components aboard satellites, is useful at both high and low temperatures and exhibits low-vacuum volatility and low shrinkage. System uses polyfunctional epoxy with high aromatic content, low equivalent weight, and more compact polymer than conventional bisphenol A tape.

  6. Candida biofilms: is adhesion sexy?

    PubMed

    Soll, David R

    2008-08-26

    The development of Candida albicans biofilms requires two types of adhesion molecule - the Als proteins and Hwp1. Mutational analyses have recently revealed that these molecules play complementary roles, and their characteristics suggest that they may have evolved from primitive mating agglutinins.

  7. Candida biofilms: is adhesion sexy?

    PubMed

    Soll, David R

    2008-08-26

    The development of Candida albicans biofilms requires two types of adhesion molecule - the Als proteins and Hwp1. Mutational analyses have recently revealed that these molecules play complementary roles, and their characteristics suggest that they may have evolved from primitive mating agglutinins. PMID:18727911

  8. Photoresist substrate having robust adhesion

    DOEpatents

    Dentinger, Paul M.

    2005-07-26

    A substrate material for LIGA applications w hose general composition is Ti/Cu/Ti/SiO.sub.2. The SiO.sub.2 is preferably applied to the Ti/Cu/Ti wafer as a sputtered coating, typically about 100 nm thick. This substrate composition provides improved adhesion for epoxy-based photoresist materials, and particularly the photoresist material SU-8.

  9. Unfolding Grammars in Adhesive Categories

    NASA Astrophysics Data System (ADS)

    Baldan, Paolo; Corradini, Andrea; Heindel, Tobias; König, Barbara; Sobociński, Paweł

    We generalize the unfolding semantics, previously developed for concrete formalisms such as Petri nets and graph grammars, to the abstract setting of (single pushout) rewriting over adhesive categories. The unfolding construction is characterized as a coreflection, i.e. the unfolding functor arises as the right adjoint to the embedding of the category of occurrence grammars into the category of grammars.

  10. Fluorescence Reveals Contamination From Adhesives

    NASA Technical Reports Server (NTRS)

    Nikolia, William

    1992-01-01

    Contamination of nearby surfaces from ingredients in some adhesive materials detected by ultraviolet illumination and observation of resulting fluorescence. Identification of contaminants via telltale fluorescence not new; rather, significance lies in method of implementation and potential extension to wider variety of materials and applications.

  11. Computational Chemistry of Adhesive Bonds

    NASA Technical Reports Server (NTRS)

    Phillips, Donald H.

    1999-01-01

    This investigation is intended to determine the electrical mechanical, and chemical properties of adhesive bonds at the molecular level. The initial determinations will be followed by investigations of the effects of environmental effects on the chemistry and properties of the bond layer.

  12. Tackifier Dispersions to Make Pressure Sensitive Adhesives

    SciTech Connect

    2003-02-01

    Development of new processes for tackifier dispersion could improve the production of pressure sensitive adhesives. Pressure sensitive adhesives (PSAs) have the ability to adhere to different surfaces with manual or finger pressure.

  13. Self-Adjustable Adhesion of Polyampholyte Hydrogels.

    PubMed

    Roy, Chanchal Kumar; Guo, Hong Lei; Sun, Tao Lin; Ihsan, Abu Bin; Kurokawa, Takayuki; Takahata, Masakazu; Nonoyama, Takayuki; Nakajima, Tasuku; Gong, Jian Ping

    2015-12-01

    Developing nonspecific, fast, and strong adhesives that can glue hydrogels and biotissues substantially promotes the application of hydrogels as biomaterials. Inspired by the ubiquitous adhesiveness of bacteria, it is reported that neutral polyampholyte hydrogels, through their self-adjustable surface, can show rapid, strong, and reversible adhesion to charged hydrogels and biological tissues through the Coulombic interaction.

  14. Nonwoven glass fiber mat reinforces polyurethane adhesive

    NASA Technical Reports Server (NTRS)

    Roseland, L. M.

    1967-01-01

    Nonwoven glass fiber mat reinforces the adhesive properties of a polyurethane adhesive that fastens hardware to exterior surfaces of aluminum tanks. The mat is embedded in the uncured adhesive. It ensures good control of the bond line and increases the peel strength.

  15. Effects of marine n-3 fatty acids on circulating levels of soluble adhesion molecules in patients with chronic heart failure.

    PubMed

    Eschen, O; Christensen, J H; LA Rovere, M T; Romano, P; Sala, P; Schmidt, E B

    2010-01-01

    Inflammatory markers as circulating soluble cellular adhesion molecules (sCAMs) and high sensitive C-reactive protein (hsCRP) are elevated in patients with chronic heart failure (CHF), and may constitute an increased risk of adverse outcome. Marine n-3 polyunsaturated fatty acids ( n-3 PUFA) may have anti-inflammatory effect and reduce levels of sCAMs (soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1), P-selectin) and hsCRP. In a randomized, controlled trial, 138 patients with NYHA class II-III CHF were allocated to receive a daily supplement of 0.9 g of n-3 PUFA or olive oil for 24 weeks. After supplementation, no significant changes occurred in sCAMs or hsCRP after adjusting for possible confounders. However, a significant reduction was observed in sP-selectin in patients receiving n-3 PUFA, but this result was only of borderline significance in a between-group analysis. In conclusion, a daily supplement with 0.9 g of n-3 PUFA does not significantly affect plasma levels of sCAMs or hs-CRP in patients with CHF. n-3 PUFA may reduce sP-selectin, indicating a possible effect on platelet (and endothelial) activation. The results also indicate that the low dose of n-3 PUFA used in many intervention trials does not have deleterious effects on sCAMs or hsCRP.

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

    SciTech Connect

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

    2012-08-24

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

  17. Ceramic adhesive restorations and biomimetic dentistry: tissue preservation and adhesion.

    PubMed

    Tirlet, Gil; Crescenzo, Hélène; Crescenzo, Dider; Bazos, Panaghiotis

    2014-01-01

    Thanks to sophisticated adhesive techniques in contemporary dentistry, and the development of composite and ceramic materials, it is possible to reproduce a biomimetic match between substitution materials and natural teeth substrates. Biomimetics or bio-emulation allows for the association of two fundamental parameters at the heart of current therapeutic treatments: tissue preservation and adhesion. This contemporary concept makes the retention of the integrity of the maximum amount of dental tissue possible, while offering exceptional clinical longevity, and maximum esthetic results. It permits the conservation of the biological, esthetic, biomechanical and functional properties of enamel and dentin. Today, it is clearly possible to develop preparations allowing for the conservation of the enamel and dentin in order to bond partial restorations in the anterior and posterior sectors therefore limiting, as Professor Urs Belser from Geneva indicates, "the replacement of previous deficient crowns and devitalized teeth whose conservation are justified but whose residual structural state are insufficient for reliable bonding."1 This article not only addresses ceramic adhesive restoration in the anterior area, the ambassadors of biomimetic dentistry, but also highlights the possibility of occasionally integrating one or two restorations at the heart of the smile as a complement to extensive rehabilitations that require more invasive treatment.

  18. Ceramic adhesive restorations and biomimetic dentistry: tissue preservation and adhesion.

    PubMed

    Tirlet, Gil; Crescenzo, Hélène; Crescenzo, Dider; Bazos, Panaghiotis

    2014-01-01

    Thanks to sophisticated adhesive techniques in contemporary dentistry, and the development of composite and ceramic materials, it is possible to reproduce a biomimetic match between substitution materials and natural teeth substrates. Biomimetics or bio-emulation allows for the association of two fundamental parameters at the heart of current therapeutic treatments: tissue preservation and adhesion. This contemporary concept makes the retention of the integrity of the maximum amount of dental tissue possible, while offering exceptional clinical longevity, and maximum esthetic results. It permits the conservation of the biological, esthetic, biomechanical and functional properties of enamel and dentin. Today, it is clearly possible to develop preparations allowing for the conservation of the enamel and dentin in order to bond partial restorations in the anterior and posterior sectors therefore limiting, as Professor Urs Belser from Geneva indicates, "the replacement of previous deficient crowns and devitalized teeth whose conservation are justified but whose residual structural state are insufficient for reliable bonding."1 This article not only addresses ceramic adhesive restoration in the anterior area, the ambassadors of biomimetic dentistry, but also highlights the possibility of occasionally integrating one or two restorations at the heart of the smile as a complement to extensive rehabilitations that require more invasive treatment. PMID:25126616

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

    PubMed

    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.

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

    PubMed

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

    2015-01-01

    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. PMID:26393541

  1. Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound interleukin-7.

    PubMed

    Ariel, A; Hershkoviz, R; Cahalon, L; Williams, D E; Akiyama, S K; Yamada, K M; Chen, C; Alon, R; Lapidot, T; Lider, O

    1997-10-01

    The putative effects of interleukin (IL)-7, operating in the context of extracellular matrix (ECM), on the adhesion of human T cells were examined. Recombinant human, IL-7 was found to bind ECM or fibronectin (FN) with IC50 values of 10-100 nM. Nanogram amounts of both soluble and, especially, FN- or ECM-bound IL-7, which differentially affected the morphologies of FN-adherent T cells, induced the adhesion of resting CD4+ and CD8+ T cells in dose-dependent and beta 1 integrin-dependent manners. Under static and flow conditions, soluble IL-7 also induced the binding of unstimulated T cells to vascular cell adhesion molecule-1, suggesting that this cytokine can also modulate integrin binding to endothelial cell ligands. The effects of affinity modulation by IL-7 of FN-specific beta 1 integrins depend on the presence of soluble FN, which inhibited T cell adhesion to FN induced by FN-bound IL-7 or by an integrin-specific affinity-modulating monoclonal antibody, but not by soluble IL-7 or phorbol 12-myristate 13-acetate. These findings provide an example of a major ECM integrin ligand, FN, which is capable of modulating its adhesive interactions with specific immune cells by associating with and presenting a cytokine in a bio-active state. PMID:9368611

  2. Gecko adhesion pad: a smart surface?

    NASA Astrophysics Data System (ADS)

    Pesika, Noshir S.; Zeng, Hongbo; Kristiansen, Kai; Zhao, Boxin; Tian, Yu; Autumn, Kellar; Israelachvili, Jacob

    2009-11-01

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  3. Gecko adhesion pad: a smart surface?

    PubMed

    Pesika, Noshir S; Zeng, Hongbo; Kristiansen, Kai; Zhao, Boxin; Tian, Yu; Autumn, Kellar; Israelachvili, Jacob

    2009-11-18

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  4. Nanocapillary Adhesion between Parallel Plates.

    PubMed

    Cheng, Shengfeng; Robbins, Mark O

    2016-08-01

    Molecular dynamics simulations are used to study capillary adhesion from a nanometer scale liquid bridge between two parallel flat solid surfaces. The capillary force, Fcap, and the meniscus shape of the bridge are computed as the separation between the solid surfaces, h, is varied. Macroscopic theory predicts the meniscus shape and the contribution of liquid/vapor interfacial tension to Fcap quite accurately for separations as small as two or three molecular diameters (1-2 nm). However, the total capillary force differs in sign and magnitude from macroscopic theory for h ≲ 5 nm (8-10 diameters) because of molecular layering that is not included in macroscopic theory. For these small separations, the pressure tensor in the fluid becomes anisotropic. The components in the plane of the surface vary smoothly and are consistent with theory based on the macroscopic surface tension. Capillary adhesion is affected by only the perpendicular component, which has strong oscillations as the molecular layering changes.

  5. Particle adhesion in powder coating

    SciTech Connect

    Mazumder, M.K.; Wankum, D.L.; Knutson, M.; Williams, S.; Banerjee, S.

    1996-12-31

    Electrostatic powder coating is a widely used industrial painting process. It has three major advantages: (1) it provides high quality durable finish, (2) the process is environmentally friendly and does not require the use of organic solvents, and (3) it is economically competitive. The adhesion of electrostatically deposited polymer paint particles on the grounded conducting substrate depends upon many parameters: (a) particle size and shape distributions, (b) electrostatic charge distributions, (c) electrical resistivity, (d) dielectric strength of the particles, (e) thickness of the powder film, (f) presence and severity of the back corona, and (g) the conductivity and surface properties of the substrate. The authors present a model on the forces of deposition and adhesion of corona charged particles on conducting substrates.

  6. Nanocapillary Adhesion between Parallel Plates.

    PubMed

    Cheng, Shengfeng; Robbins, Mark O

    2016-08-01

    Molecular dynamics simulations are used to study capillary adhesion from a nanometer scale liquid bridge between two parallel flat solid surfaces. The capillary force, Fcap, and the meniscus shape of the bridge are computed as the separation between the solid surfaces, h, is varied. Macroscopic theory predicts the meniscus shape and the contribution of liquid/vapor interfacial tension to Fcap quite accurately for separations as small as two or three molecular diameters (1-2 nm). However, the total capillary force differs in sign and magnitude from macroscopic theory for h ≲ 5 nm (8-10 diameters) because of molecular layering that is not included in macroscopic theory. For these small separations, the pressure tensor in the fluid becomes anisotropic. The components in the plane of the surface vary smoothly and are consistent with theory based on the macroscopic surface tension. Capillary adhesion is affected by only the perpendicular component, which has strong oscillations as the molecular layering changes. PMID:27413872

  7. Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

    PubMed

    Lee, Miryoung; Czerwinski, Stefan A; Choh, Audrey C; Demerath, Ellen W; Sun, Shumei S; Chumlea, Wm C; Towne, Bradford; Siervogel, Roger M

    2006-03-01

    Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

  8. Nerve growth factor translates stress response and subsequent murine abortion via adhesion molecule-dependent pathways.

    PubMed

    Tometten, Mareike; Blois, Sandra; Kuhlmei, Arne; Stretz, Anna; Klapp, Burghard F; Arck, Petra C

    2006-04-01

    Spontaneous abortion is a frequent threat affecting 10%-25% of human pregnancies. Psychosocial stress has been suggested to be attributable for pregnancy losses by challenging the equilibrium of systems mandatory for pregnancy maintenance, including the nervous, endocrine, and immune system. Strong evidence indicates that stress-triggered abortion is mediated by adhesion molecules, i.e., intercellular adhesion molecule 1 (ICAM1) and leukocyte function associated molecule 1, now being referred to as integrin alpha L (ITGAL), which facilitate recruitment of inflammatory cells to the feto-maternal interface. The neurotrophin beta-nerve growth factor (NGFB), which has been shown to be upregulated in response to stress in multiple experimental settings including in the uterine lining (decidua) during pregnancy, increases ICAM1 expression on endothelial cells. Here, we investigated whether and how NGFB neutralization has a preventive effect on stress-triggered abortion in the murine CBA/J x DBA/2J model. We provide experimental evidence that stress exposure upregulates the frequency of abortion and the expression of uterine NGFB. Further, adhesion molecules ICAM1 and selectin platelet (SELP, formerly P-Selectin) and their ligands ITGAL and SELP ligand (SELPL, formerly P selectin glycoprotein ligand 1) respectively increase in murine deciduas in response to stress. Subsequently, decidual cytokines are biased toward a proinflammatory and abortogenic cytokine profile. Additionally, a decrease of pregnancy protective CD8alpha(+) decidual cells is present. Strikingly, all such uterine stress responses are abrogated by NGFB neutralization. Hence, NGFB acts as a proximal mediator in the hierarchical network of immune rejection by mediating an abortogenic environment comprised of classical signs of neurogenic inflammation. PMID:16371592

  9. Concentration of soluble adhesion molecules in cerebrospinal fluid and serum of epilepsy patients.

    PubMed

    Luo, Jing; Wang, Wei; Xi, Zhiqin; Dan, Chen; Wang, Liang; Xiao, Zheng; Wang, Xuefeng

    2014-12-01

    Mounting evidence supports the involvement of brain inflammation and the associated blood-brain barrier damage from which spontaneous and recurrent seizures originate. Detection of the soluble form of adhesion molecules (AM) has also been proven to predict outcomes in central nervous system (CNS) disorders. A recent study has shown that expression of AM in brain vessels was upregulated 24 h after kainic acid (KA) induced seizures. The aim of the present study was to investigate soluble AM levels in the cerebrospinal fluid (CSF) and serum of epilepsy patients. Paired CSF and serum samples were analyzed by sandwich enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Increased serum concentrations of sICAM-1 were present in epileptic patients (41 localization-related of unknown etiology, 19 idiopathic generalized). Serum sICAM-1 level in drug-refractory epilepsy was elevated as compared to new diagnosis epilepsy and drug-responsive epilepsy. CSF sVCAM-1 and serum sVCAM-1 concentrations in the epilepsy group were higher as compared to the neurosis group. Moreover, CSF sVCAM-1 and serum sVCAM-1 concentrations in drug-refractory epilepsy were raised as compared to drug-responsive epilepsy and new diagnosis epilepsy. However, there were no significant differences in concentrations of CSF sICAM-1 between the epilepsy and neurosis groups. Our results suggest that sVCAM-1 and sICAM-1 could play an important role in the drug-refractory epilepsy. PMID:25001004

  10. Host Selection of Microbiota via Differential Adhesion.

    PubMed

    McLoughlin, Kirstie; Schluter, Jonas; Rakoff-Nahoum, Seth; Smith, Adrian L; Foster, Kevin R

    2016-04-13

    The host epithelium is the critical interface with microbial communities, but the mechanisms by which the host regulates these communities are poorly understood. Here we develop the hypothesis that hosts use differential adhesion to select for and against particular members of their microbiota. We use an established computational, individual-based model to study the impact of host factors that regulate adhesion at the epithelial surface. Our simulations predict that host-mediated adhesion can increase the competitive advantage of microbes and create ecological refugia for slow-growing species. We show how positive selection via adhesion can be transformed into negative selection if the host secretes large quantities of a matrix such as mucus. Our work predicts that adhesion is a powerful mechanism for both positive and negative selection within the microbiota. We discuss molecules-mucus glycans and IgA-that affect microbe adhesion and identify testable predictions of the adhesion-as-selection model. PMID:27053168

  11. Theory of adhesion: Role of surface roughness

    NASA Astrophysics Data System (ADS)

    Persson, B. N. J.; Scaraggi, M.

    2014-09-01

    We discuss how surface roughness influences the adhesion between elastic solids. We introduce a Tabor number which depends on the length scale or magnification, and which gives information about the nature of the adhesion at different length scales. We consider two limiting cases relevant for (a) elastically hard solids with weak (or long ranged) adhesive interaction (DMT-limit) and (b) elastically soft solids with strong (or short ranged) adhesive interaction (JKR-limit). For the former cases we study the nature of the adhesion using different adhesive force laws (F ˜ u-n, n = 1.5-4, where u is the wall-wall separation). In general, adhesion may switch from DMT-like at short length scales to JKR-like at large (macroscopic) length scale. We compare the theory predictions to results of exact numerical simulations and find good agreement between theory and simulation results.

  12. Adhesive mechanisms in cephalopods: a review.

    PubMed

    von Byern, Janek; Klepal, Waltraud

    2006-01-01

    Several genera of cephalopods (Nautilus, Sepia, Euprymna and Idiosepius) produce adhesive secretions, which are used for attachment to the substratum, for mating and to capture prey. These adhesive structures are located in different parts of the body, viz. in the digital tentacles (Nautilus), in the ventral surface of the mantle and fourth arm pair (Sepia), in the dorsal epidermis (Euprymna), or in the dorsal mantle side and partly on the fins (Idiosepius). Adhesion in Sepia is induced by suction of dermal structures on the mantle, while for Nautilus, Euprymna and Idiosepius adhesion is probably achieved by chemical substances. Histochemical studies indicate that in Nautilus and Idiosepius secretory cells that appear to be involved in adhesion stain for carbohydrates and protein, whilst in Euprymna only carbohydrates are detectable. De-adhesion is either achieved by muscle contraction of the tentacles and mantle (Nautilus and Sepia) or by secretion of substances (Euprymna). The de-adhesive mechanism used by Idiosepius remains unknown. PMID:17110356

  13. Adhesion effects in contact interaction of solids

    NASA Astrophysics Data System (ADS)

    Goryacheva, Irina; Makhovskaya, Yulya

    2008-01-01

    An approach to solving problems of the interaction of axisymmetric elastic bodies in the presence of adhesion is developed. The different natures of adhesion, i.e. capillary adhesion, or molecular adhesion described by the Lennard-Jones potential are examined. The effect of additional loading of the interacting bodies outside the contact zone is also investigated. The approach is based on the representation of the pressure outside the contact zone arising from adhesion by a step function. The analytical solution is obtained and is used to analyze the influence of the form of the adhesion interaction potential, of the surface energy of interacting bodies or the films covering the bodies, their shapes (parabolic, higher power exponential function), volume of liquid in the meniscus, density of contact spots, of elastic modulus and the Poisson ratio on the characteristics of the interaction of the bodies in the presence of adhesion. To cite this article: I. Goryacheva, Y. Makhovskaya, C. R. Mecanique 336 (2008).

  14. Adhesive mechanisms in cephalopods: a review.

    PubMed

    von Byern, Janek; Klepal, Waltraud

    2006-01-01

    Several genera of cephalopods (Nautilus, Sepia, Euprymna and Idiosepius) produce adhesive secretions, which are used for attachment to the substratum, for mating and to capture prey. These adhesive structures are located in different parts of the body, viz. in the digital tentacles (Nautilus), in the ventral surface of the mantle and fourth arm pair (Sepia), in the dorsal epidermis (Euprymna), or in the dorsal mantle side and partly on the fins (Idiosepius). Adhesion in Sepia is induced by suction of dermal structures on the mantle, while for Nautilus, Euprymna and Idiosepius adhesion is probably achieved by chemical substances. Histochemical studies indicate that in Nautilus and Idiosepius secretory cells that appear to be involved in adhesion stain for carbohydrates and protein, whilst in Euprymna only carbohydrates are detectable. De-adhesion is either achieved by muscle contraction of the tentacles and mantle (Nautilus and Sepia) or by secretion of substances (Euprymna). The de-adhesive mechanism used by Idiosepius remains unknown.

  15. Approaching improved adhesive bonding repeatability

    NASA Astrophysics Data System (ADS)

    Schlette, Christian; Müller, Tobias; Roβmann, Jürgen; Brecher, Christian

    2016-03-01

    Today, the precision of micro-optics assembly is mostly limited by the accuracy of the bonding process ― and in the case of adhesive bonding by the prediction and compensation of adhesive shrinkage during curing. In this contribution, we present a novel approach to address adhesive bonding based on hybrid control system theory. In hybrid control, dynamic systems are described as "plants" which produce discrete and/or continuous outputs from given discrete and/or continuous inputs, thus yielding a hybrid state space description of the system. The task of hybrid controllers is to observe the plant and to generate a discrete and/or continuous input sequence that guides or holds the plant in a desired target state region while avoiding invalid or unwanted intermediate states. Our approach is based on a series of experiments carried out in order to analyze, define and decouple the dependencies of adhesive shrinkage on multiple parameters, such as application geometries, fixture forces and UV intensities. As some of the dependencies describe continuous effects (e.g. shrinkage from UV intensity) and other dependencies describe discrete state transitions (e.g. fixture removal during curing), the resulting model of the overall bonding process is a hybrid dynamic system in the general case. For this plant model, we then propose a concept of sampling-based parameter search as a basis to design suitable hybrid controllers, which have the potential to optimize process control for a selection of assembly steps, thus improving the repeatability of related production steps like beam-shaping optics or mounting of turning mirrors for fiber coupling.

  16. Polymer nanocarriers for dentin adhesion.

    PubMed

    Osorio, R; Osorio, E; Medina-Castillo, A L; Toledano, M

    2014-12-01

    To obtain more durable adhesion to dentin, and to protect collagen fibrils of the dentin matrix from degradation, calcium- and phosphate-releasing particles have been incorporated into the dental adhesive procedure. The aim of the present study was to incorporate zinc-loaded polymeric nanocarriers into a dental adhesive system to facilitate inhibition of matrix metalloproteinases (MMPs)-mediated collagen degradation and to provide calcium ions for mineral deposition within the resin-dentin bonded interface. PolymP- N : Active nanoparticles (nanoMyP) were zinc-loaded through 30-minute ZnCl2 immersion and tested for bioactivity by means of 7 days' immersion in simulated body fluid solution (the Kokubo test). Zinc-loading and calcium phosphate depositions were examined by scanning and transmission electron microscopy, elemental analysis, and x-ray diffraction. Nanoparticles in ethanol solution infiltrated into phosphoric-acid-etched human dentin and Single Bond (3M/ESPE) were applied to determine whether the nanoparticles interfered with bonding. Debonded sticks were analyzed by scanning electron microscopy. A metalloproteinase collagen degradation assay was also performed in resin-infiltrated dentin with and without nanoparticles, measuring C-terminal telopeptide of type I collagen (ICTP) concentration in supernatants, after 4 wk of immersion in artificial saliva. Numerical data were analyzed by analysis of variance (ANOVA) and Student-Newman-Keuls multiple comparisons tests (p < .05). Nanoparticles were effectively zinc-loaded and were shown to have a chelating effect, retaining calcium regardless of zinc incorporation. Nanoparticles failed to infiltrate demineralized intertubular dentin and remained on top of the hybrid layer, without altering bond strength. Calcium and phosphorus were found covering nanoparticles at the hybrid layer, after 24 h. Nanoparticle application in etched dentin also reduced MMP-mediated collagen degradation. Tested nanoparticles may be

  17. Culinary Medicine-Jalebi Adhesions.

    PubMed

    Kapoor, Vinay K

    2016-02-01

    Culinary terms have been used to describe anatomy (bean-shaped kidneys), pathology (strawberry gall bladder), clinical signs (café-au-lait spots), radiological images (sausage-shaped pancreas), etc. While Indian cuisine is popular all over the world, no Indian dish finds mention in medical terminology. In intra-abdominal adhesions, sometimes, the intestinal loops are so densely adherent that it is difficult to make out proximal from distal and it is impossible to separate them without injuring the bowel resulting in spill of contents-resection is the only option (Fig. 1). Jalebi, an Indian dessert, has a single long tubular strip of fried batter filled with sugary syrup so intertwined that it is impossible to discern its ends; if broken, the syrup spills out-the best way to relish it is to chew the whole piece (Fig. 2). Because of these similarities between them, I propose to name dense intra-abdominal adhesions as 'jalebi adhesions.' PMID:27186047

  18. Adhesive evaluation of new polyimides

    NASA Technical Reports Server (NTRS)

    Stclair, Terry L.; Progar, Donald J.

    1987-01-01

    During the past 10 to 15 years, the Materials Division at NASA Langley Research Center (LaRC) has developed several novel high temperature polyimide adhesives for anticipated needs of the aerospace industry. These developments have resulted from fundamental studies of structure-property relationships in polyimides. Recent research at LaRC has involved the synthesis and evaluation of copolyimides which incorporate both flexibilizing bridging groups and meta-linked benzene rings. The purpose was to develop systems based on low cost, readily available monomers. Two of these copolyimides evaluated as adhesives for bonding titanium alloy, Ti(6Al-4V), are identified as LARC-STPI and STPI-LARC-2. Lap shear strength (LSS) measurements were used to determine the strength and durability of the adhesive materials. LSS results are presented for LARC-TPI and LARC-STPI lap shear specimens thermally exposed in air at 232 C for up to 5000 hrs. LARC-TPI was shown to perform better than the copolymer LARC-STPI which exhibited poor thermooxidative performance possibly due to the amines used which would tend to oxidize easier than the benzophenone system in LARC-TPI.

  19. Effect of propane-2-sulfonic acid octadec-9-enyl-amide on the expression of adhesion molecules in human umbilical vein endothelial cells.

    PubMed

    Chen, Cai-Xia; Yang, Li-Chao; Xu, Xu-Dong; Wei, Xiao; Gai, Ya-Ting; Peng, Lu; Guo, Han; Hao-Zhou; Wang, Yi-Qing; Jin, Xin

    2015-06-01

    Oleoylethanolamide (OEA), an endogenous agonist of PPARα, has been reported to have anti-atherosclerotic properties. However, OEA can be enzymatically hydrolyzed to oleic acid and ethanolamine and, thus, is not expected to be orally active. In the present study, we designed and synthesized an OEA analog, propane-2-sulfonic acid octadec-9-enyl-amide (N15), which is resistant to enzymatic hydrolysis. The purpose of this study was to investigate the effects of N15 on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results showed that N15 inhibited TNFα-induced production of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and the adhesion of monocytes to TNFα-induced HUVECs. Furthermore, the protective effect of N15 on inflammation is dependent upon a PPAR-α/γ-mediated mechanism. In conclusion, N15 protects against TNFα-induced vascular endothelial inflammation. This anti-inflammatory effect of N15 is dependent on PPAR-α/γ dual targets.

  20. Increased erythrocyte adhesion to VCAM-1 during pulsatile flow: Application of a microfluidic flow adhesion bioassay

    PubMed Central

    White, Jennell; Lancelot, Moira; Sarnaik, Sharada; Hines, Patrick

    2015-01-01

    Abstract Sickle cell disease (SCD) is characterized by microvascular occlusion mediated by adhesive interactions of sickle erythrocytes (SSRBCs) to the endothelium. Most in vitro flow adhesion assays measure SSRBC adhesion during continuous flow, although in vivo SSRBC adhesive interactions occur during pulsatile flow. Using a well-plate microfluidic flow adhesion system, we demonstrate that isolated SSRBCs adhere to vascular cell adhesion molecule (VCAM-1) at greater levels during pulsatile versus continuous flow. A significant increase in adhesive interactions was observed between all pulse frequencies 1 Hz to 2 Hz (60–120 beats/min) when compared to non-pulsatile flow. Adhesion of isolated SSRBCs and whole blood during pulsatile flow was unaffected by protein kinase A (PKA) inhibition, and exposure of SSRBCs to pulsatile flow did not affect the intrinsic adhesive properties of SSRBCs. The cell type responsible for increased adhesion of whole blood varied from patient to patient. We conclude that low flow periods of the pulse cycle allow more adhesive interactions between sickle erythrocytes and VCAM-1, and sickle erythrocyte adhesion in the context of whole blood may better reflect physiologic cellular interactions. The microfluidic flow adhesion bioassay used in this study may have applications for clinical assessment of sickle erythrocyte adhesion during pulsatile flow. PMID:24898561

  1. Functional Mineralocorticoid Receptors in Human Vascular Endothelial Cells Regulate ICAM-1 Expression and Promote Leukocyte Adhesion

    PubMed Central

    Caprio, Massimiliano; Newfell, Brenna G.; la Sala, Andrea; Baur, Wendy; Fabbri, Andrea; Rosano, Giuseppe; Mendelsohn, Michael E.; Jaffe, Iris Z.

    2008-01-01

    In clinical trials, aldosterone antagonists decrease cardiovascular mortality and ischemia by unknown mechanisms. The steroid hormone aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor. In humans, aldosterone causes MR-dependent endothelial cell (EC) dysfunction and in animal models, aldosterone increases vascular macrophage infiltration and atherosclerosis. MR antagonists inhibit these effects without changing blood pressure, suggesting a direct role for vascular MR in EC function and atherosclerosis. Whether human vascular EC express functional MR is not known. Here we show that human coronary artery and aortic EC express MR mRNA and protein and that EC MR mediates aldosterone-dependent gene transcription. Human EC also express the enzyme 11-beta hydroxysteroid dehydrogenase-2(11βHSD2) and inhibition of 11βHSD2 in aortic EC enhances gene transactivation by cortisol, supporting that EC 11βHSD2 is functional. Furthermore, aldosterone stimulates transcription of the proatherogenic leukocyte-EC adhesion molecule Intercellular Adhesion Molecule-1(ICAM1) gene and protein expression on human coronary artery EC, an effect inhibited by the MR antagonist spironolactone and by MR knock-down with siRNA. Cell adhesion assays demonstrate that aldosterone promotes leukocyte-EC adhesion, an effect that is inhibited by spironolactone and ICAM1 blocking antibody, supporting that aldosterone induction of EC ICAM1 surface expression via MR mediates leukocyte-EC adhesion. These data show that aldosterone activates endogenous EC MR and proatherogenic gene expression in clinically important human EC. These studies describe a novel mechanism by which aldosterone may influence ischemic cardiovascular events and support a new explanation for the decrease in ischemic events in patients treated with aldosterone antagonists. PMID:18467630

  2. Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains.

    PubMed

    Perez de Arce, Karen; Schrod, Nikolas; Metzbower, Sarah W R; Allgeyer, Edward; Kong, Geoffrey K-W; Tang, Ai-Hui; Krupp, Alexander J; Stein, Valentin; Liu, Xinran; Bewersdorf, Jörg; Blanpied, Thomas A; Lucić, Vladan; Biederer, Thomas

    2015-12-16

    The cleft is an integral part of synapses, yet its macromolecular organization remains unclear. We show here that the cleft of excitatory synapses exhibits a distinct density profile as measured by cryoelectron tomography (cryo-ET). Aiming for molecular insights, we analyzed the synapse-organizing proteins Synaptic Cell Adhesion Molecule 1 (SynCAM 1) and EphB2. Cryo-ET of SynCAM 1 knockout and overexpressor synapses showed that this immunoglobulin protein shapes the cleft's edge. SynCAM 1 delineates the postsynaptic perimeter as determined by immunoelectron microscopy and super-resolution imaging. In contrast, the EphB2 receptor tyrosine kinase is enriched deeper within the postsynaptic area. Unexpectedly, SynCAM 1 can form ensembles proximal to postsynaptic densities, and synapses containing these ensembles were larger. Postsynaptic SynCAM 1 surface puncta were not static but became enlarged after a long-term depression paradigm. These results support that the synaptic cleft is organized on a nanoscale into sub-compartments marked by distinct trans-synaptic complexes.

  3. IRF-1 regulates alternative mRNA splicing of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in breast epithelial cells generating an immunoreceptor tyrosine-based inhibition motif (ITIM) containing isoform

    PubMed Central

    2014-01-01

    Background Interferon regulatory factor-1 (IRF-1) is a master regulator of IFN-γ induced gene transcription. Previously we have shown that IRF-1 transcriptionally induces CEACAM1 via an ISRE (Interferon-Stimulated Response Element) in its promoter. CEACAM1 pre-mRNA undergoes extensive alternative splicing (AS) generating isoforms to produce either a short (S) cytoplasmic domain expressed primarily in epithelial cells or as an ITIM-containing long (L) isoform in immune cells. Methods The transcriptional and molecular mechanism of CEACAM1 minigenes AS containing promoter ISREs mutations in the breast epithelial, MDA-MB-468, cell line was detected using flow cytometry. In addition, transcriptome sequencing was utilized to determine whether IRF-1 could direct the AS of other genes as well. Tumor xenografts were used to evaluate CEACAM1 isoform expression on the leading edge of breast tumor cells. Results In the present study, we provide evidence that CEACAM1’s promoter and variable exon 7 cross-talk allowing IRF-1 to direct AS events. Transcriptome sequencing shows that IRF-1 can also induce the global AS of genes involved in regulation of growth and differentiation as well as genes of the cytokine family. Furthermore, MDA-MB-468 cells grown as tumor xenografts exhibit an AS switch to the L-isoform of CEACAM1, demonstrating that an in vivo inflammatory milieu is also capable of generating the AS switch, similar to that found in human breast cancers Mol Cancer 7:46, 2008. Conclusions The novel AS regulatory activities attributed to IRF-1 indicate that the IFN-γ response involves a global change in both gene transcription and AS in breast epithelial cells. PMID:24650050

  4. Chitosan Adhesive Films for Photochemical Tissue Bonding

    NASA Astrophysics Data System (ADS)

    Lauto, Antonio; Mawad, Damia; Barton, Matthew; Piller, Sabine C.; Longo, Leonardo

    2011-08-01

    Photochemical tissue bonding (PTB) is a promising sutureless technique for tissue repair. PTB is often achieved by applying a solution of rose bengal (RB) between two tissue edges, which are irradiated by a green laser to crosslink collagen fibers with minimal heat production. In this study, RB has been incorporated in chitosan films to create a novel tissue adhesive that is laser-activated. Materials and Methods. Adhesive films, based on chitosan and containing ˜0.1wt% RB were manufactured and bonded to calf intestine by a solid state laser (wavelength = 532 nm, Fluence ˜110 J/cm2, spot size ˜5 mm). A single-column tensiometer, interfaced with a personal computer, tested the bonding strength. K-type thermocouples recorded the temperature (T) at the adhesive-tissue interface during laser irradiation. Human fibroblasts were also seeded on the adhesive and cultured for 48 hours to assess cell growth. Results and Conclusion. The RB-chitosan adhesive bonded firmly to the intestine (15±2 kPa, n = 31). The adhesion strength dropped to 0.5±0.1 kPa (n = 8) when the laser was not applied to the adhesive. The average temperature of the adhesive increased from 26 °C to 32 °C during laser exposure. Fibroblasts grew confluent on the adhesive without morphological changes. A new biocompatible chitosan adhesive has been developed that bonds photochemically to tissue with minimal temperature increase.

  5. Sundew adhesive: a naturally occurring hydrogel

    PubMed Central

    Huang, Yujian; Wang, Yongzhong; Sun, Leming; Agrawal, Richa; Zhang, Mingjun

    2015-01-01

    Bioadhesives have drawn increasing interest in recent years, owing to their eco-friendly, biocompatible and biodegradable nature. As a typical bioadhesive, sticky exudate observed on the stalked glands of sundew plants aids in the capture of insects and this viscoelastic adhesive has triggered extensive interests in revealing the implied adhesion mechanisms. Despite the significant progress that has been made, the structural traits of the sundew adhesive, especially the morphological characteristics in nanoscale, which may give rise to the viscous and elastic properties of this mucilage, remain unclear. Here, we show that the sundew adhesive is a naturally occurring hydrogel, consisting of nano-network architectures assembled with polysaccharides. The assembly process of the polysaccharides in this hydrogel is proposed to be driven by electrostatic interactions mediated with divalent cations. Negatively charged nanoparticles, with an average diameter of 231.9 ± 14.8 nm, are also obtained from this hydrogel and these nanoparticles are presumed to exert vital roles in the assembly of the nano-networks. Further characterization via atomic force microscopy indicates that the stretching deformation of the sundew adhesive is associated with the flexibility of its fibrous architectures. It is also observed that the adhesion strength of the sundew adhesive is susceptible to low temperatures. Both elasticity and adhesion strength of the sundew adhesive reduce in response to lowering the ambient temperature. The feasibility of applying sundew adhesive for tissue engineering is subsequently explored in this study. Results show that the fibrous scaffolds obtained from sundew adhesive are capable of increasing the adhesion of multiple types of cells, including fibroblast cells and smooth muscle cells, a property that results from the enhanced adsorption of serum proteins. In addition, in light of the weak cytotoxic activity exhibited by these scaffolds towards a variety of

  6. Adhesion enhancement of biomimetic dry adhesives by nanoparticle in situ synthesis

    NASA Astrophysics Data System (ADS)

    Díaz Téllez, J. P.; Harirchian-Saei, S.; Li, Y.; Menon, C.

    2013-10-01

    A novel method to increase the adhesion strength of a gecko-inspired dry adhesive is presented. Gold nanoparticles are synthesized on the tips of the microfibrils of a polymeric dry adhesive to increase its Hamaker constant. Formation of the gold nanoparticles is qualitatively studied through a colour change in the originally transparent substance and quantitatively analysed using ultraviolet-visible spectrophotometry. A pull-off force test is employed to quantify the adhesion enhancement. Specifically, adhesion forces of samples with and without embedded gold nanoparticles are measured and compared. The experimental results indicate that an adhesion improvement of 135% can be achieved.

  7. Differential changes in platelet reactivity induced by acute physical compared to persistent mental stress.

    PubMed

    Hüfner, Katharina; Koudouovoh-Tripp, Pia; Kandler, Christina; Hochstrasser, Tanja; Malik, Peter; Giesinger, Johannes; Semenitz, Barbara; Humpel, Christian; Sperner-Unterweger, Barbara

    2015-11-01

    Platelets are important in hemostasis, but also contain adhesion molecules, pro-inflammatory and immune-modulatory compounds, as well as most of the serotonin outside the central nervous system. Dysbalance in the serotonin pathways is involved in the pathogenesis of depressive symptoms. Thus, changes in platelet aggregation and content of bioactive compounds are of interest when investigating physiological stress-related mental processes as well as stress-related psychiatric diseases such as depression. In the present study, a characterization of platelet reactivity in acute physical and persistent mental stress was performed (aggregation, serotonin and serotonin 2A-receptor, P-selectin, CD40 ligand, matrix metalloproteinase-2 and -9 (MMP-2 and -9), platelet/endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), β-thromboglobulin (β-TG) and platelet factor 4 (PF-4). Acute physical stress increased platelet aggregability while leaving platelet content of bioactive compounds unchanged. Persistent mental stress led to changes in platelet content of bioactive compounds and serotonin 2A-receptor only. The values of most bioactive compounds correlated with each other. Acute physical and persistent mental stress influences platelets through distinct pathways, leading to differential changes in aggregability and content of bioactive compounds. PMID:26192713

  8. Alpha-melanocyte stimulating hormone inhibits monocytes adhesion to vascular endothelium

    PubMed Central

    Yang, Yang; Zhang, Weihua; Meng, Lin; Yu, Haitao; Lu, Na; Fu, Gang

    2015-01-01

    Inflammation and its subsequent endothelial dysfunction have been reported to play a pivotal role in the initiation and progression of chronic vascular diseases. Inhibiting the attachment of monocytes to endothelium is a potential therapeutic strategy for vascular diseases treatment. α-Melanocyte stimulating hormone is generated from a precursor hormone called proopiomelanocortin by post-translational processing. However, whether α-melanocyte stimulating hormone plays a role in regulating endothelial inflammation is still unknown. In this study, the effects of α-melanocyte stimulating hormone on endothelial inflammation in human umbilical vein endothelial cell lines were investigated. And the result indicated that α-melanocyte stimulating hormone inhibits the expression of endothelial adhesion molecules, including vascular adhesion molecule-1 and E-selectin, thereby attenuating the adhesion of THP-1 cells to the surface of endothelial cells. Mechanistically, α-melanocyte stimulating hormone was found to inhibit NF-κB transcriptional activity. Finally, we found that the effect of α-melanocyte stimulating hormone on endothelial inflammation is dependent on its receptor melanocortin receptor 1. PMID:25898835

  9. Dehydrodiconiferyl alcohol suppresses monocyte adhesion to endothelial cells by attenuation of JNK signaling pathway.

    PubMed

    Tsuneyoshi, Tadamitsu; Kanamori, Yuta; Matsutomo, Toshiaki; Morihara, Naoaki

    2015-09-25

    Several clinical studies have shown that the intake of aged garlic extract improves endothelial dysfunction. Lignan compounds, (+)-(2S,3R)-dehydrodiconiferyl alcohol (DDC) and (-)-(2R,3S)-dihydrodehydrodiconiferyl alcohol (DDDC), have been isolated as antioxidants in aged garlic extract. There is evidence showing the importance of oxidative stress in endothelial dysfunction. In the present study, we examined whether DDC and DDDC enhance endothelial cell function in vitro. Cell adhesion assay was performed using THP-1 monocyte and human umbilical vein endothelial cells (HUVECs) which were activated by lipopolysaccharide (LPS) or advanced glycation end products (AGEs)-BSA. Cellular ELISA method was used for the evaluation of vascular cell adhesion molecule 1 (VCAM-1) expression on HUVECs. DDC and DDDC suppressed the adhesion of THP-1 to HUVECs which was activated by LPS or AGEs-BSA. DDC and DDDC also inhibited VCAM-1 expression induced by LPS or AGEs-BSA, but DDDC was less effective than DDC. In addition, the inhibitory effect of DDC on VCAM-1 expression involved suppressing JNK/c-Jun pathway rather than NF-κB pathway. DDC has an inhibitory effect on VCAM-1 expression via JNK pathway in endothelial cells and therefore may serve as a novel pharmacological agent to improve endothelial dysfunction. PMID:26271597

  10. [Allergens-induced sensitization alters airway epithelial adhesion molecules expression in mice].

    PubMed

    Zeng, Dan; Tan, Mei-Ling; Xiang, Yang; Qin, Xiao-Qun; Zhu, Li-Ming; Dai, Ai-Guo

    2015-12-25

    To explore the relationship between the epithelial adhesion molecules and immune responses of airway epithelium, we observed the expression of integrin β4 and intercellular adhesion molecule-1 (ICAM-1) in the mice airway epithelium after sensitization with allergens. BALB/c mice were sensitized with intraperitoneal injection of ovalbumin (OVA) or house dust mite (HDM) and then developed airway hyper-responsiveness as determined by barometric whole-body plethysmography. Both OVA and HDM sensitization led to increases of the number of peripheral leukocytes as well as inflammatory cells infiltration in lungs. OVA sensitized mice showed more severe inflammatory cells infiltration than HDM sensitized mice. Immunohistochemistry analysis of mice lung tissues revealed that sensitization with both allergens also led to a decrease of integrin β4 expression and an increase of ICAM-1 expression in airway epithelia. OVA sensitized mice showed a more significant increase of ICAM-1 expression compared with HDM sensitized mice. siRNA mediated silencing of integrin β4 gene in 16HBE cells resulted in an up-regulation of ICAM-1 expression. Our results indicate a possible role of airway epithelial adhesion molecules in allergen-induced airway immune responses. PMID:26701635

  11. Proteomic dataset of the sea urchin Paracentrotus lividus adhesive organs and secreted adhesive.

    PubMed

    Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

    2016-06-01

    Sea urchins have specialized adhesive organs called tube feet, which mediate strong but reversible adhesion. Tube feet are composed by a disc, producing adhesive and de-adhesive secretions for substratum attachment, and a stem for movement. After detachment the secreted adhesive remains bound to the substratum as a footprint. Recently, a label-free quantitative proteomic approach coupled with the latest mass-spectrometry technology was used to analyze the differential proteome of Paracentrotus lividus adhesive organ, comparing protein expression levels in the tube feet adhesive part (the disc) versus the non-adhesive part (the stem), and also to profile the proteome of the secreted adhesive (glue). This data article contains complementary figures and results related to the research article "Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: a quantitative proteomics approach" (Lebesgue et al., 2016) [1]. Here we provide a dataset of 1384 non-redundant proteins, their fragmented peptides and expression levels, resultant from the analysis of the tube feet differential proteome. Of these, 163 highly over-expressed tube feet disc proteins (>3-fold), likely representing the most relevant proteins for sea urchin reversible adhesion, were further annotated in order to determine the potential functions. In addition, we provide a dataset of 611 non-redundant proteins identified in the secreted adhesive proteome, as well as their functional annotation and grouping in 5 major protein groups related with adhesive exocytosis, and microbial protection. This list was further analyzed to identify the most abundant protein groups and pinpoint putative adhesive proteins, such as Nectin, the most abundant adhesive protein in sea urchin glue. The obtained data uncover the key proteins involved in sea urchins reversible adhesion, representing a step forward to the development of new wet-effective bio-inspired adhesives.

  12. Proteomic dataset of the sea urchin Paracentrotus lividus adhesive organs and secreted adhesive.

    PubMed

    Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

    2016-06-01

    Sea urchins have specialized adhesive organs called tube feet, which mediate strong but reversible adhesion. Tube feet are composed by a disc, producing adhesive and de-adhesive secretions for substratum attachment, and a stem for movement. After detachment the secreted adhesive remains bound to the substratum as a footprint. Recently, a label-free quantitative proteomic approach coupled with the latest mass-spectrometry technology was used to analyze the differential proteome of Paracentrotus lividus adhesive organ, comparing protein expression levels in the tube feet adhesive part (the disc) versus the non-adhesive part (the stem), and also to profile the proteome of the secreted adhesive (glue). This data article contains complementary figures and results related to the research article "Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: a quantitative proteomics approach" (Lebesgue et al., 2016) [1]. Here we provide a dataset of 1384 non-redundant proteins, their fragmented peptides and expression levels, resultant from the analysis of the tube feet differential proteome. Of these, 163 highly over-expressed tube feet disc proteins (>3-fold), likely representing the most relevant proteins for sea urchin reversible adhesion, were further annotated in order to determine the potential functions. In addition, we provide a dataset of 611 non-redundant proteins identified in the secreted adhesive proteome, as well as their functional annotation and grouping in 5 major protein groups related with adhesive exocytosis, and microbial protection. This list was further analyzed to identify the most abundant protein groups and pinpoint putative adhesive proteins, such as Nectin, the most abundant adhesive protein in sea urchin glue. The obtained data uncover the key proteins involved in sea urchins reversible adhesion, representing a step forward to the development of new wet-effective bio-inspired adhesives. PMID:27182547

  13. Cilostazol prevents remnant lipoprotein particle-induced monocyte adhesion to endothelial cells by suppression of adhesion molecules and monocyte chemoattractant protein-1 expression via lectin-like receptor for oxidized low-density lipoprotein receptor activation.

    PubMed

    Park, So Youn; Lee, Jeong Hyun; Kim, Yong Ki; Kim, Chi Dae; Rhim, Byung Yong; Lee, Won Suk; Hong, Ki Whan

    2005-03-01

    This study shows cilostazol effect to prevent remnant lipoprotein particle (RLP)-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). Upon incubation of HUVECs with RLP (50 microg/ml), adherent monocytes significantly increased by 3.3-fold with increased cell surface expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Cilostazol ( approximately 1-100 microM) concentration dependently repressed these variables as did (E)3-[(4-t-butylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7085) (10 microM), a specific nuclear factor-kappaB (NF-kappaB) inhibitor. Cilostazol effects were significantly antagonized by iberiotoxin (1 microM), a maxi-K channel blocker. RLP significantly increased expression of lectin-like receptor for oxidized low-density lipoprotein (LDL) (LOX-1) receptor protein. Upon transfection with antisense LOX-1 oligodeoxynucleotide (As-LOX-1), LOX-1 receptor expression was reduced, whereas HUVECs with sense LOX-1 oligodeoxynucleotide did express high LOX-1 receptor. RLP-stimulated superoxide and tumor necrosis factor-alpha levels were significantly lowered with decreased expression of VCAM-1 and MCP-1 by transfection with As-LOX-1 as did polyinosinic acid (10 microg/ml, a LOX-1 receptor inhibitor). RLP significantly degraded inhibitory kappaBalpha in the cytoplasm and activated nuclear factor-kappaB (NF-kappaB) p65 in the nucleus of HUVECs with increased luciferase activity of NF-kappaB, all of which were reversed by cilostazol (10 microM), BAY 11-7085, and polyinosinic acid. Together, cilostazol suppresses RLP-stimulated increased monocyte adhesion to HUVECs by suppression of LOX-1 receptor-coupled NF-kappaB-dependent nuclear transcription via mediation of the maxi-K channel opening.

  14. A batch fabricated biomimetic dry adhesive

    NASA Astrophysics Data System (ADS)

    Northen, Michael T.; Turner, Kimberly L.

    2005-08-01

    The fine hair adhesive system found in nature is capable of reversibly adhering to just about any surface. This dry adhesive, best demonstrated in the pad of the gecko, makes use of a multilevel conformal structure to greatly increase inelastic surface contact, enhancing short range interactions and producing significant amounts of attractive forces. Recent work has attempted to reproduce and test the terminal submicrometre 'hairs' of the system. Here we report the first batch fabricated multi-scale conformal system to mimic nature's dry adhesive. The approach makes use of massively parallel MEMS processing technology to produce 20-150 µm platforms, supported by single slender pillars, and coated with ~2 µm long, ~200 nm diameter, organic looking polymer nanorods, or 'organorods'. To characterize the structures a new mesoscale nanoindenter adhesion test technique has been developed. Experiments indicate significantly improved adhesion with the multiscale system. Additional processing caused a hydrophilic to hydrophobic transformation of the surface and testing indicated further improvement in adhesion.

  15. Functionally Graded Adhesives for Composite Joints

    NASA Technical Reports Server (NTRS)

    Stapleton, Scott E.; Waas, Anthony M.; Arnold, Steven M.

    2012-01-01

    Adhesives with functionally graded material properties are being considered for use in adhesively bonded joints to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. An enhanced joint finite element, which uses an analytical formulation to obtain exact shape functions, is used to model the joint. Furthermore, proof of concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint.

  16. Adhesive curing through low-voltage activation

    NASA Astrophysics Data System (ADS)

    Ping, Jianfeng; Gao, Feng; Chen, Jian Lin; Webster, Richard D.; Steele, Terry W. J.

    2015-08-01

    Instant curing adhesives typically fall within three categories, being activated by either light (photocuring), heat (thermocuring) or chemical means. These curing strategies limit applications to specific substrates and can only be activated under certain conditions. Here we present the development of an instant curing adhesive through low-voltage activation. The electrocuring adhesive is synthesized by grafting carbene precursors on polyamidoamine dendrimers and dissolving in aqueous solvents to form viscous gels. The electrocuring adhesives are activated at -2 V versus Ag/AgCl, allowing tunable crosslinking within the dendrimer matrix and on both electrode surfaces. As the applied voltage discontinued, crosslinking immediately terminated. Thus, crosslinking initiation and propagation are observed to be voltage and time dependent, enabling tuning of both material properties and adhesive strength. The electrocuring adhesive has immediate implications in manufacturing and development of implantable bioadhesives.

  17. Synaptic Cell Adhesion Molecules in Alzheimer's Disease

    PubMed Central

    Leshchyns'ka, Iryna

    2016-01-01

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

  18. Adhesive curing through low-voltage activation

    PubMed Central

    Ping, Jianfeng; Gao, Feng; Chen, Jian Lin; Webster, Richard D.; Steele, Terry W. J.

    2015-01-01

    Instant curing adhesives typically fall within three categories, being activated by either light (photocuring), heat (thermocuring) or chemical means. These curing strategies limit applications to specific substrates and can only be activated under certain conditions. Here we present the development of an instant curing adhesive through low-voltage activation. The electrocuring adhesive is synthesized by grafting carbene precursors on polyamidoamine dendrimers and dissolving in aqueous solvents to form viscous gels. The electrocuring adhesives are activated at −2 V versus Ag/AgCl, allowing tunable crosslinking within the dendrimer matrix and on both electrode surfaces. As the applied voltage discontinued, crosslinking immediately terminated. Thus, crosslinking initiation and propagation are observed to be voltage and time dependent, enabling tuning of both material properties and adhesive strength. The electrocuring adhesive has immediate implications in manufacturing and development of implantable bioadhesives. PMID:26282730

  19. Mussel-Inspired Adhesives and Coatings

    PubMed Central

    Lee, Bruce P.; Messersmith, P.B.; Israelachvili, J.N.; Waite, J.H.

    2011-01-01

    Mussels attach to solid surfaces in the sea. Their adhesion must be rapid, strong, and tough, or else they will be dislodged and dashed to pieces by the next incoming wave. Given the dearth of synthetic adhesives for wet polar surfaces, much effort has been directed to characterizing and mimicking essential features of the adhesive chemistry practiced by mussels. Studies of these organisms have uncovered important adaptive strategies that help to circumvent the high dielectric and solvation properties of water that typically frustrate adhesion. In a chemical vein, the adhesive proteins of mussels are heavily decorated with Dopa, a catecholic functionality. Various synthetic polymers have been functionalized with catechols to provide diverse adhesive, sealant, coating, and anchoring properties, particularly for critical biomedical applications. PMID:22058660

  20. NR-150B2 adhesive development

    NASA Technical Reports Server (NTRS)

    Blatz, P. S.

    1978-01-01

    Adhesive based polyimide solutions which are more easily processed than conventional aromatic polyimide systems and show potential for use for extended times at 589K are discussed. The adhesive system is based on a solution containing diglyme as the solvent and 2,2 bis(3',4'-dicarboxyphenyl)hexafluoropropane, paraphenylenediamine, and oxydianiline. The replacement of N-methylpyrrolidone with diglyme as the solvent was found to improve the adhesive strengths of lap shear samples and simplify the processing conditions for bonding both titanium and graphite fiber/polyimide matrix resin composites. Information was obtained on the effects of various environments including high humidity, immersion in jet fuel and methylethylketone on aluminum filled adhesive bonds. The adhesive was also evaluated in wide area bonds and flatwise tensile specimens using titanium honeycomb and composite face sheets. It was indicated that the developed adhesive system has the potential for use in applications requiring long term exposure to at least 589K (600 F).

  1. Adhesion and wear resistance of materials

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.

    1986-01-01

    Recent studies into the nature of bonding at the interface between two solids in contact or a solid and deposited film have provided a better understanding of those properties important to the adhesive wear resistance of materials. Analytical and experimental progress are reviewed. For simple metal systems the adhesive bond forces are related to electronic wave function overlap. With metals in contact with nonmetals, molecular-orbital energy, and density of states, respectively can provide insight into adhesion and wear. Experimental results are presented which correlate adhesive forces measured between solids and the electronic surface structures. Orientation, surface reconstruction, surface segregation, adsorption are all shown to influence adhesive interfacial strength. The interrelationship between adhesion and the wear of the various materials as well as the life of coatings applied to substrates are discussed. Metallic systems addressed include simple metals and alloys and these materials in contact with themselves, both oxide and nonoxide ceramics, diamond, polymers, and inorganic coating compounds, h as diamondlike carbon.

  2. Innate Non-Specific Cell Substratum Adhesion

    PubMed Central

    Loomis, William F.; Fuller, Danny; Gutierrez, Edgar; Groisman, Alex; Rappel, Wouter-Jan

    2012-01-01

    Adhesion of motile cells to solid surfaces is necessary to transmit forces required for propulsion. Unlike mammalian cells, Dictyostelium cells do not make integrin mediated focal adhesions. Nevertheless, they can move rapidly on both hydrophobic and hydrophilic surfaces. We have found that adhesion to such surfaces can be inhibited by addition of sugars or amino acids to the buffer. Treating whole cells with αlpha-mannosidase to cleave surface oligosaccharides also reduces adhesion. The results indicate that adhesion of these cells is mediated by van der Waals attraction of their surface glycoproteins to the underlying substratum. Since glycoproteins are prevalent components of