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At least 1,063 records · Page 59Linked to original sources
PubMed2002

Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration.

Previous studies demonstrated that integrin alpha(M)beta(2) (CD11b/18, Mac-1) forms a physical complex with the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes. In this study, we used human peripheral blood neutrophils and transfected cells expressing alpha(M)beta(2), uPAR, or both receptors to show that the integrin can directly interact with urokinase (uPA). We demonstrate that alpha(M)beta(2) supported adhesion and migration of these cells to uPA, and, in each case, blockade of alpha(M)beta(2) suppressed the response. Within uPA, both the kringle and proteolytic domains are recognized by alpha(M)beta(2), which are distinct from the growth factor domain that binds to uPAR. Within the alpha(M) subunit of the integrin, the I domain interacts with uPA, which is distinct from the region that interacts with uPAR. On cells expressing uPAR and alpha(M)beta(2), both receptors mediated adhesion and migration. This cooperation was particularly apparent in the responses of neutrophils to uPA, where blockade of alpha(M)beta(2) reduced uPAR-mediated responses and engagement of uPAR enhanced recognition of uPA by alpha(M)beta(2). Thus, recognition of uPA by alpha(M)beta(2) allows for formation of a multicontact trimolecular complex, in which a single uPA ligand may bind simultaneously to both uPAR and alpha(M)beta(2). This complex may play an important role in the control of inflammatory cell migration and vascular homeostasis.

Cell Adhesion↗
PubMed2003

The cell adhesion molecules N-cadherin and neural cell adhesion molecule regulate human growth hormone: a novel mechanism for regulating pituitary hormone secretion.

Pituitary GH secretion is regulated by hypothalamic hormones and peripheral factors. Cell-cell contact may also have an important role in regulating pituitary hormone expression and secretion. The role of pituicyte cell-cell contact mediated by N-cadherin and neural cell adhesion molecule (N-CAM) was studied in the regulation of GH secretion. RT-PCR showed N-cadherin mRNA expression in eight of 12 of GH-secreting adenomas compared with one of seven of prolactin-cell adenomas. N-cadherin and N-CAM were similarly expressed in adenomas and in adult and fetal normal pituitary tissues. The effects of CAM homophilic binding on GH secretion from dispersed human fetal pituitary cultures were studied by manipulating CAM mediated cell-cell contact using either soluble N-cadherin-Fc or pituitary cells cocultured with NIH-3T3 cells stably expressing CAMs. CAM stimulation increased GH secretion from pituitary fetal cultures by 40-60% (P < 0.05) and also from cultured GH adenoma cells by 40-75% (P < 0.05). Disrupting N-cadherin homophilic binding by anti-N-cadherin antibody decreased fetal, but not tumorous GH secretion by 40% (P < 0.05). This study indicates that pituitary cell-cell contact mediated by homophilic interactions between adhesion molecules regulates human GH secretion.

3T3 Cells↗
PubMed2003

The therapeutic effects of epidural intercellular adhesion molecule-1 monoclonal antibody in a rabbit model: involvement of the intercellular adhesion molecule-1 pathway in spinal cord ischemia.

The pathophysiology of ischemia/reperfusion injury involves extravascular migration of leukocytes from the bloodstream to the site of injury. Leukocyte adhesion and intercellular adhesion molecule-1 (ICAM-1) play an important role in the recruitment of leukocytes to the site of injury. In this study, we evaluated the role of the ICAM-1 in spinal cord ischemia and the therapeutic effects of epidural ICAM-1 monoclonal antibody (Mab). The descending aorta was occluded below the renal artery with an aneurysm clip in rabbits anesthetized with halothane. The following variables were evaluated, in addition to ICAM-1 expression in the lumbar spinal cord, in animals receiving saline or ICAM-1 Mab via the epidural route: (1) leukocyte recruitment in the lumen of capillary vessels of the lumbar spinal cord (L6-7) at 8 h after 30 min of aortic occlusion and (2) neurological evaluation at 20 h after aortic occlusion of 10, 15, 17.5, 20, or 25 min. Paraplegia was graded with the following scale: Grade 0, no deficit; Grade 1, partial deficit; and Grade 2, complete paraplegia. Spinal cord ischemia increased the expression of ICAM-1 in the endothelium of spinal cord capillaries and led to capillary leukocyte recruitment and extravascular migration into the lumbar spinal cord parenchyma, which was ablated with epidural ICAM-1 Mab. Epidural ICAM-1 Mab reduced neurological deficits and offered neuroprotection. These findings demonstrate the involvement of the ICAM-1 pathway in spinal cord ischemia and the neuroprotective effects of epidural ICAM-1 Mab. Strategies to ameliorate spinal cord ischemia may entail the administration of leukocyte antiadhesion molecules into the neuraxial space.

Acute-Phase Reaction↗
PubMed1988

Cell-adhesion and substrate-adhesion molecules: their instructive roles in neural crest cell migration.

The individualization of crest cells from the neural folds and neural tube involves distinct mechanisms affecting both the tissue shape and the cell environment. Though these mechanisms are not fully understood at the molecular level, the analysis of the distribution of several molecules reported to promote intercellular contacts indicates a correlation between cell detachment from the neurepithelium and the decrease of cell adhesion molecule expression. During the following phase of migration, the mode of adhesion of crest cells switches preferentially to the cell-to-substratum type. Various experiments showed that among the major extracellular matrix components, fibronectins were decisive in promoting cell attachment, spreading and motility. Additional studies on receptors for fibronectins gave new insights on the differences between a motile and a stationary cell. These results will be discussed with particular reference to the migration at the cephalic level where most perturbation experiments were performed. The molecular biology of fibronectins provided a finer understanding of the interactions between a cell and these molecules. The tools derived from this technique will open new areas of investigation hopefully leading to a better understanding of (i) the regulation of the cell-fibronectins interaction and (ii) the specificity of the pathways of migration followed by migrating cells, like the descendants of the neural crest.

Animals↗
PubMed2005

Modulating the strength of cadherin adhesion: evidence for a novel adhesion complex.

Adherens junctions and desmosomes are critical for embryogenesis and the integrity of adult tissues. To form these junctions, classical cadherins interact via alpha- and beta-catenin with the actin cytoskeleton, whereas desmosomal cadherins interact with the intermediate filament system. Here, we used a hormone-activated mutant N-cadherin expressed in fibroblasts to show the existence of a novel classical cadherin adhesion system. N-cadherin was fused at its C-terminus to a modified estrogen receptor ligand-binding domain (NcadER) that binds 4-hydroxytamoxifen (4OHT) and expressed in L cells, which lack an endogenous cadherin. Cells with the mutant cadherin (LNER cells) aggregated in the absence of 4OHT, but only in its presence formed tightly compacted aggregates like those formed by L cells expressing wild-type N-cadherin (LN cells). Compaction of LNER cells treated with 4OHT was accompanied by elevated levels of p120ctn in NcadER immunoprecipitates, compared to immunoprecipitates of non-treated cells, but without changes in alpha- and beta-catenin, or actin. Compaction induced by 4OHT was also accompanied by increased interaction of the NcadER with the cytoskeleton and increased vimentin organization. Vimentin co-immunoprecipitated with the NcadER/catenin complex, suggesting an interaction between cadherin and vimentin. The mechanism by which vimentin interacts with the cadherin appears to involve p120ctn as it co-immunoprecipitates and colocalizes with vimentin in the parent L cells, which lack a cadherin and alpha- and beta-catenins. Disrupting the actin cytoskeleton with cytochalasin B inhibited aggregation, whereas knocking down vimentin with specific siRNAs inhibited compaction. Based on our results we propose that a vimentin-based classical cadherin complex functions together with the actin-based complex to promote strong cell-cell adhesion in fibroblasts.

Actins↗
PubMed1991

Corneal cell adhesion and proliferation on hydrogel sheets bound with cell-adhesive proteins.

The efficiency of protein immobilization to provide a hydrogel surface with a high affinity for corneal epithelial cells was investigated. The cell adhesive proteins collagen and fibronectin, and the cell adhesive oligopeptide RGDS (arginine-glycine-aspartic acid-serine) were successfully covalently immobilized on poly(vinyl alcohol) (PVA) hydrogel sheets. Corneal epithelial cells and L-929 cells were applied to these surfaces. A large number of cells did adhere and proliferate on these protein-bound surfaces in comparison with the virgin PVA not so immobilized.

Amino Acid Sequence↗
PubMed1990

Differential spectrum of expression of neural cell adhesion molecule isoforms and L1 adhesion molecules on human neuroectodermal tumors.

A series of four medulloblastomas, seven neuroblastomas (Nb), two ependymomas, and three gliomas, human neuroectodermal tumors, were screened for their expression of adhesion molecules L1, carcinoembryonic antigen, neural cell adhesion molecule isoforms (N-CAM) and HNK1 epitope by Western blotting and double immunofluorescence labeling. All seven neuroblastomas, whatever their differentiated state, expressed L1, a neural cell surface developmental antigen, whereas all other tumors tested were negative. All tumors expressed N-CAM; however, a large diversity was observed among the isoforms. Low sialylated N-CAM 140 was present, with different intensity, in ependymomas and astrocytomas. High sialylated isoforms were detected by a monoclonal antibody (anti-MenB) specifically recognizing high polymers of alpha 2-8 linked neuraminic acid. They were expressed in all medulloblastomas studied (4 of 4), and in 4 of 7 Nbs examined. Negative cases corresponded to tumors having undergone chemotherapeutic treatment or to ganglioneuroma. The interconversion from high to low sialylated forms might reflect changes which are critical for the conversion of Nbs into benign ganglioneuromas. HNK1 epitope was expressed on a large diversity of molecules by nearly all tumors except two Nbs which were also negative with anti-MenB antibody. This simultaneous loss of carbohydrate epitopes could correlate with higher maturation states of the tumors. None of the tumors expressed carcinoembryonic antigen. Therefore, anti-L1 and anti-MenB antibodies define differentiation-related antigens that could differentiate between Nbs and other tumors and may prove helpful in diagnosis and understanding of the biological nature of neuroectodermal tumors. An immunodot assay was set up and allowed to titrate the presence of polysialic acid units in cerebrospinal fluid from patients presenting meningeal spread of medulloblastomas. It could help to assess metastasis and to monitor the effects of chemotherapeutic treatment on polysialylated N-CAM positive tumors.

Adult↗
PubMed1988

Presence of the long chain form of polysialic acid of the neural cell adhesion molecule in Wilms' tumor. Identification of a cell adhesion molecule as an oncodevelopmental antigen and implications for tumor histogenesis.

The long chain form of polysialic acid characteristic of the low adhesive embryonic form of the neural cell adhesion molecule NCAM is temporally and spatially expressed in developing kidney but undetectable in normal adult kidney. Therefore, this molecule represents a developmentally regulated antigen in kidney contrasted with neural tissue, where it is also detectable in the adult brain. This investigation of 25 Wilms' tumors comprising all different histologic types demonstrates expression of this molecule under conditions of malignant growth. Immunostaining was observed in Wilms' tumors with both a monoclonal anti-polysialic acid antibody and a polyclonal anti-NCAM polypeptide antiserum. Intense cell surface staining sensitive to endosialidases specifically hydrolyzing alpha 2,8 linked (poly)sialic acid was detectable in blastemal regions, and weaker, variable labeling was seen over tubules and glomeruloid bodies. The stroma was not stained. This is evidence indicating that Wilms' tumor originates from the embryonic equivalent of induced metanephrogenic mesenchyme. It seems unlikely however, that the stroma is derived from the blastema. The same high molecular mass broad band typical of the embryonic form of NCAM was revealed by immunoblot analysis of homogenates from Wilms' tumor as well as from embryonic kidney and brain. In situ hybridization demonstrated the presence of mRNA for NCAM in all but stromal elements of Wilm's tumors. Thus, polysialic acid is present on NCAM and represents a new oncodevelopmental antigen in human kidney. Polysialic acid was greatly reduced or absent by immunohistochemistry and immunoblotting in necrotic tumor areas.

Adult↗
PubMedDate not supplied

Adhesion-to-skin performance of a new transdermal nitroglycerin adhesive patch.

Six men and six women participated in a study designed to compare adhesion-to-skin measurements of three transdermal nitroglycerin patch formulations (Minitran, Transderm-Nitro 5, and Nitro-Dur II) with an occlusive surgical tape control. After 24 hours of wear, Minitran was found to be superior to the other three products in skin adhesion. The force required to remove Minitran was significantly higher than that required to remove the other products. Maintaining good skin contact over the entire application period is essential for consistent drug delivery. Improved skin contact can increase transdermal drug delivery. This increase in delivery of nitroglycerin may result in the development of smaller patches rated to deliver the same quantity of nitroglycerin over a 24-hour period.

Adhesiveness↗
PubMed1986

Oligodendrocyte cell adhesion molecules are related to neural cell adhesion molecule (N-CAM).

The glycoproteins responsible for calcium-dependent oligodendrocyte aggregation were purified and characterized. Using detergent extraction, lentil-lectin-Sepharose 4B affinity chromatography, and preparative gel electrophoresis, 3 proteins were purified to apparent homogeneity, with relative Mrs of 120,000, 140,000, and 180,000. The aggregation assay showed that all 3 proteins had the ability to block antibody-mediated inhibition of oligodendrocyte aggregation. The 120,000 protein was the most active of the three. Antisera were raised in rabbits to these 3 individual proteins. Western blot analyses showed that all three antisera recognized 120,000, 140,000, and 180,000 proteins, which indicated that the proteins were related. Western-blot analyses of cultured oligodendrocytes and purified rat myelin showed only the 120,000 protein. Immunoprecipitation of iodinated membrane proteins of cultured oligodendrocytes also indicated the presence of only the 120,000 Mr protein. Deglycosylation of the 120,000 protein by N-glycanase resulted in a 110,000 protein. The immunoblot pattern suggested some similarities between oligodendrocyte adhesion molecules and the neural cell adhesion molecule (N-CAM). Therefore, the 120,000, 140,000, and 180,000 Mr proteins were compared to N-CAM by Western-blot analysis, immunofluorescence staining, and by immunoprecipitation. The results suggest that oligodendrocytes contain a 120,000 membrane glycoprotein that is related to N-CAM.

Animals↗
PubMed1982

Intercellular adhesion of rat hepatocytes. Identification of a cell surface glycoprotein involved in the initial adhesion process.

A cell surface molecule involved in intercellular adhesion between rat hepatocytes in vitro has been identified. Papain-solubilized plasma membrane components were fractionated; the ability of the solubilized components to neutralize the inhibition of cell aggregation, caused by multispecific antibodies directed against the cell surface, was used to follow the purification. The purified components were used to immunize rabbits. The resulting antibodies effectively inhibited hepatocyte aggregation, and this inhibitory effect could be neutralized by detergent-solubilized plasma membrane components having an apparent molecular weight of 105,000 in polyacrylamide gel electrophoresis. Also by immunoprecipitation, immunoblotting, and immunosorbent techniques it was demonstrated that the antibodies specifically reacted with a plasma membrane component having an apparent molecular weight of 105,000. This component was susceptible to digestion with papain and showed specific binding to the carbohydrate-binding lectin Lens culinaris hemagglutinin. It was thus concluded that a glycoprotein with a mass of about 105,000 daltons is involved in rat hepatocyte intercellular adhesion.

Animals↗
PubMed1994

Effects of anti-CD44 monoclonal antibody on adhesion of erythroid leukemic cells (ELM-I-1) to hematopoietic supportive cells (MS-5): CD44, but not hyaluronate-mediated, cell-cell adhesion.

Cocultivation of erythroid leukemic cells (ELM-I-1) with hemopoietic supportive cells (MS-5) resulted in a specific adhesion of ELM-I-1 cells to MS-5 cells. This phenomenon was designated as rosette formation. After induction of differentiation of ELM-I-1 cells, rosette formation was reduced, and no rosette formation was observed between erythrocytes and MS-5 cells. Studies on anti-adhesion molecule antibody treatment have revealed that CD44 plays a key role in rosette formation. Expression of CD44 on (the membrane of) ELM-I-1 cells was reduced after differentiation, and no CD44 expression was detected on erythrocytes. CD44 was also expressed on MS-5. Hyaluronate is known as the ligand of CD44, but neither hyaluronidase treatment nor addition of excess hyaluronate to the assay system affected rosette formation. These data indicate that hyaluronate is not responsible for rosette formation. Anti-CD44 antibody (KM81), which recognized the hyaluronate binding site of CD44, inhibited rosette formation. But other monoclonal antibodies against different epitopes except for the hyaluronate binding site, even those against CD44's hyaluronate binding site, did not inhibit rosette formation. Thus, rosette formation between MS-5 cells and ELM-I-1 cells is mediated by CD44 but not by the hyaluronate binding site of CD44.

Animals↗
PubMed1993

[Changes in the adhesive capacity of the substrates during the IgG- and C3b-dependent adhesion of polymorphonuclear leukocytes].

The capacity of IgG-sepharose, C3b-sephadex and DEAE-sephadex to adsorb human neutrophils after repeated contacts with these cells was studied. A reduction of neutrophil adhesion was found only in experiments with receptor-dependent sorbents (IgG-sepharose, C3b-sephadex). The reduction of adsorption capacity of neutrophil IgG-sepharose was not due to products secreted by cells into the incubation medium or to IgG elimination from the sorbent surface. The data are considered to be a result of ligand molecules modification at the point of neutrophil adhesion contacts with the substrate. The role of this mechanism in neutrophil desorption process is discussed.

Cell Adhesion↗
PubMedDate not supplied

Preoperative serum intercellular adhesion molecule-1 (ICAM-1) and E-selectin (endothelial cell leukocyte adhesion molecule, ELAM-1) in patients with epithelial ovarian cancer.

The serum levels of intercellular adhesion molecule-1 (ICAM-1) and E-Selectin (endothelial cell leukocyte adhesion molecule, ELAM-1) were retrospectively measured in serum samples drawn at diagnosis from 66 patients with epithelial ovarian cancer and 128 patients with benign ovarian masses. The preoperative serum ICAM-1 levels were higher in the former group (p < 0.0001), while serum E-Selectin concentrations were similar in the two groups (p = NS). Among patients with epithelial ovarian cancer, neither serum ICAM-1 nor E-selectin levels correlated with FIGO stage and with histologic type. The serum assay of ICAM-1 and E-Selectin seems to have limited value in the management of patients with epithelial ovarian cancer.

Adult↗
PubMed1996

U-73122: a potent inhibitor of human polymorphonuclear neutrophil adhesion on biological surfaces and adhesion-related effector functions.

We have reported that U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole- 2,5-dione) an inhibitor of phospholipase C-dependent processes in human polymorphonuclear neutrophils (PMN) and platelets, potently suppresses the responsiveness of suspended PMN and platelets to receptor agonists. We demonstrate here that U-73122 caused a concentration-dependent (10-800 nM) inhibition of N-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor-alpha (TNF alpha), interleukin-8 and phorbol myristate acetate (PMA)-triggered PMN adhesion on fibronectin, fetal bovine serum or keyhole limpet hemocyanincoated microtiter plates. U-73122 also inhibited PMN adherence to and transmigration through TNF-alpha-activated endothelium (IC50 < 50 nM). Further, U-73122 suppressed interleukin-8, N-formylmethionyl-leucyl-phenylalanine and PMA-stimulated up-regulation of the beta 2-integrin, Mac-1 (CD11b/CD18), on the PMN surface (IC50 < 1.3 microM). U-73122 also caused a time-(15-120 min) and concentration-dependent inhibition (IC50 = 25-100 nM) of the N-formyl-methionyl-leucyl-phenylalanine-, TNF alpha- and PMA-elicited adhesion-dependent, oxidative burst, measured as hydrogen peroxide (H2O2) production, in PMN. The CD18-dependent extracellular release of lactoferrin from PMN activated with these stimuli was also suppressed by U-73122. U-73343 (1-[6-[[17 beta-3- methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidine dione), a close analog of U-73122, did not affect PMN responsiveness.

Animals↗
PubMed1999

Quantitative relationship among integrin-ligand binding, adhesion, and signaling via focal adhesion kinase and extracellular signal-regulated kinase 2.

Because integrin-mediated signals are transferred through a physical architecture and synergistic biochemical network whose properties are not well defined, quantitative relationships between extracellular integrin-ligand binding events and key intracellular responses are poorly understood. We begin to address this by quantifying integrin-mediated FAK and ERK2 responses in CHO cells for varied alpha(5)beta(1) expression level and substratum fibronectin density. Plating cells on fibronectin-coated surfaces initiated a transient, biphasic ERK2 response, the magnitude and kinetics of which depended on integrin-ligand binding properties. Whereas ERK2 activity initially increased with a rate proportional to integrin-ligand bond number for low fibronectin density, the desensitization rate was independent of integrin and fibronectin amount but proportional to the ERK2 activity level with an exponential decay constant of 0.3 (+/- 0.08) min(-1). Unlike the ERK2 activation time course, FAK phosphorylation followed a superficially disparate time course. However, analysis of the early kinetics of the two signals revealed them to be correlated. The initial rates of FAK and ERK2 signal generation exhibited similar dependence on fibronectin surface density, with both rates monotonically increasing with fibronectin amount until saturating at high fibronectin density. Because of this similar initial rate dependence on integrin-ligand bond formation, the disparity in their time courses is attributed to differences in feedback regulation of these signals. Whereas FAK phosphorylation increased to a steady-state level as new integrin-ligand bond formation continued during cell spreading, ERK2 activity was decoupled from the integrin-ligand stimulus and decayed back to a basal level. Accordingly, we propose different functional metrics for representing these two disparate dynamic signals: the steady-state tyrosine phosphorylation level for FAK and the integral of the pulse response for ERK2. These measures of FAK and ERK2 activity were found to correlate with short term cell-substratum adhesivity, indicating that signaling via FAK and ERK2 is proportional to the number of integrin-fibronectin bonds.

Animals↗
PubMed1996

Control of adhesion-dependent cell survival by focal adhesion kinase.

The interactions of integrins with extracellular matrix proteins can activate focal adhesion kinase (FAK) and suppress apoptosis in normal epithelial and endothelial cells; this subset of apoptosis has been termed "anoikis." Here, we demonstrate that FAK plays a role in the suppression of anoikis. Constitutively activated forms of FAK rescued two established epithelial cell lines from anoikis. Both the major autophosphorylation site (Y397) and a site critical to the kinase activity (K454) of FAK were required for this effect. Activated FAK also transformed MDCK cells, by the criteria of anchorage-independent growth and tumor formation in nude mice. We provide evidence that this transformation resulted primarily from the cells' resistance to anoikis rather than from the activation of growth factor response pathways. These results indicate that FAK can regulate anoikis and that the conferral of anoikis resistance may suffice to transform certain epithelial cells.

Animals↗