scholarly journals Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers.

1987 ◽  
Vol 104 (2) ◽  
pp. 331-342 ◽  
Author(s):  
C M Chuong ◽  
K L Crossin ◽  
G M Edelman
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Granule Cell ◽  
Cell Adhesion Molecule ◽  
Granular Layer ◽  
Molecular Layer ◽  
External Granular Layer ◽  
Cortical Layers

We have correlated the times of appearance of the neural cell adhesion molecule (N-CAM), the neuron-glia cell adhesion molecule (Ng-CAM), and the extracellular matrix protein, cytotactin, during the development of the chicken cerebellar cortex, and have shown that these molecules make different functional contributions to granule cell migration. Immunofluorescent staining showed distinct spatiotemporal expression sequences for each adhesion molecule. N-CAM was present at all times in all layers. However, the large cytoplasmic domain polypeptide of N-CAM was always absent from the external granular layer and was enriched in the molecular layer as development proceeded. Ng-CAM began to be expressed in the premigratory granule cells just before migration and later disappeared from cell bodies but remained on parallel fibers. Cytotactin, which is synthesized by glia and not by neurons, appeared first in a speckled pattern within the external granular layer and later appeared in a continuous pattern along the Bergmann glia; it was also enriched in the molecular layer. After we established their order of appearance, we tested the separate functions of these adhesion molecules in granule cell migration by adding specific antibodies against each molecule to cerebellar explant cultures that had been labeled with tritiated thymidine and then measuring the differential distribution of labeled cells in the forming layers. Anti-N-CAM showed marginal effects. In contrast, anti-Ng-CAM arrested most cells in the external granular layer, while anti-cytotactin arrested most cells in the molecular layer. Time course analyses combined with sequential addition of different antibodies in different orders showed that anti-Ng-CAM had a major effect in the early period (first 36 h in culture) and a lesser effect in the second part of the culture period, while anti-cytotactin had essentially no effect at the earlier time but had major effects at a later period (18-72 h in culture). The two major stages of cerebellar granule cell migration thus appear to be differentially affected by distinct adhesion molecules of different cellular origins, binding mechanisms, and overall distributions. The results indicated that local cell surface modulation of adhesion molecules of different specificities at defined stages and sites is essential to the formation of cerebellar cortical layers.

Abstract 452: Serine Carboxypeptidase 1 Mediates Vascular Remodeling by Increasing Inflammatory Cell Infiltration

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ting-Hein Lee ◽  
Joseph Miano
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Remodeling ◽  
Cell Adhesion Molecule ◽  
Inflammatory Cell ◽  
Catalytic Triad ◽  
Serine Carboxypeptidase ◽  
Cell Adhesion Molecule 1

In pathological vascular remodeling, contractile vascular smooth muscle cells (VSMCs) switch their phenotype to highly proliferative and migratory states leading to neointimal formation. Inflammatory cell recruitment and infiltration, which is dependent on the increased expression of adhesion molecules on the endothelial cells, is a key event to initiate SMC phenotypic modulation in vascular remodeling. Serine carboxypeptidase 1 (scpep1), a novel protease containing the putative catalytic triad (Ser-Asp-His) common to all members of the serine protease family, has been proved to be involved in vascular remodeling by promoting SMC proliferation and migration in a catalytic triad-dependent manner. To determine whether Scpep1 modulates leukocyte adhesion and infiltration, a flow-induced model of vascular remodeling was conducted in wild-type (WT) or Scpep1 knockout (KO) mice. Scpep1-null mice show a decreased number of infiltrated leukocytes into the intima and media compared to WT mice. Further, mice devoid of Scpep1 show a dramatic reduction of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression in vessels in comparison with that of WT mice. Consistent with our in vivo data, the expression levels of ICAM-1 and VCAM-1 on human umbilical vein endothelial cells (HUVECs) transfected with SiRNA against Scpep1 were significantly decreased after TNF-α treatment. Taken together, these data suggest that Scpep1 may increase leukocyte extravasation by increasing the expression of VCAM-1 and ICAM-1 adhesion molecules.

scholarly journals Novel Cytokine-independent Induction of Endothelial Adhesion Molecules Regulated by Platelet/Endothelial Cell Adhesion Molecule (CD31)

1997 ◽  
Vol 139 (1) ◽  
pp. 219-228 ◽  
Author(s):  
Marek Litwin ◽  
Katherine Clark ◽  
Leanne Noack ◽  
Jill Furze ◽  
Michael Berndt ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Endothelial Cell Adhesion Molecule ◽  
L Cells ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion

Tumor necrosis factor–α, interleukin-1, and endotoxin stimulate the expression of vascular endothelial cell (EC) adhesion molecules. Here we describe a novel pathway of adhesion molecule induction that is independent of exogenous factors, but which is dependent on integrin signaling and cell–cell interactions. Cells plated onto gelatin, fibronectin, collagen or fibrinogen, or anti-integrin antibodies, expressed increased amounts of E-selectin, vascular cell adhesion molecule–1, and intercellular adhesion molecule–1. In contrast, ECs failed to express E-selectin when plated on poly-l-lysine or when plated on fibrinogen in the presence of attachment-inhibiting, cyclic Arg-Gly-Asp peptides. The duration and magnitude of adhesion molecule expression was dependent on EC density. Induction of E-selectin on ECs plated at confluent density was transient and returned to basal levels by 15 h after plating when only 7 ± 2% (n = 5) of cells were positive. In contrast, cells plated at low density displayed a 17-fold greater expression of E-selectin than did high density ECs with 57 ± 4% (n = 5) positive for E-selectin expression 15 h after plating, and significant expression still evident 72 h after plating. The confluency-dependent inhibition of expression of E-selectin was at least partly mediated through the cell junctional protein, platelet/endothelial cell adhesion molecule–1 (PECAM-1). Antibodies against PECAM-1, but not against VE-cadherin, increased E-selectin expression on confluent ECs. Co– culture of subconfluent ECs with PECAM-1– coated beads or with L cells transfected with full-length PECAM-1 or with a cytoplasmic truncation PECAM-1 mutant, inhibited E-selectin expression. In contrast, untransfected L cells or L cells transfected with an adhesion-defective domain 2 deletion PECAM-1 mutant failed to regulate E-selectin expression. In an in vitro model of wounding the wound front displayed an increase in the number of E-selectin–expressing cells, and also an increase in the intensity of expression of E-selectin positive cells compared to the nonwounded monolayer. Thus we propose that the EC junction, and in particular, the junctional molecule PECAM-1, is a powerful regulator of endothelial adhesiveness.

A Cell-Based Adhesion Molecule Bioassay Detects Unexpected Properties of Plasma From Patients with Sickle Cell Disease with Documented Pulmonary Hypertension

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2120-2120
Author(s):  
Antje Ask ◽  
Laurel G. Mendelsohn ◽  
Shoaib Alam ◽  
Alem Mehari ◽  
Caterina Minniti ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Heart Catheterization ◽  
Soluble Adhesion Molecules

Abstract Abstract 2120 Pulmonary hypertension (PH) is a common complication in adults with sickle cell disease (SCD) associated with early mortality. Several mechanistic pathways appear to be involved in PH in SCD, one of them being activation of pulmonary endothelium and increased adherence of circulation blood cells. In the past, levels of soluble adhesion molecules in the plasma of patients with SCD have been found to correlate with severity of pulmonary hypertension and risk of mortality. We investigated the association between endothelial-cell based adhesion molecules and markers of PH. We developed a new cell-based ELISA assay and evaluated the induction of cell surface expression of adhesion molecules on cultured microvascular endothelium cells by plasma from subjects with SCD who had undergone right heart catheterization. We found no difference in baseline Intercellular Cell Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1) and P-selectin induction by SCD plasma compared to healthy controls. Surprisingly, we found an inverse relationship of cell surface VCAM-1 induction with diagnosis and severity of PH, as indicated by mean pulmonary artery pressure (mPAP) on right heart catheterization. Patients who fell into the upper quartile of VCAM-1 induction had mPAP of 27.6 ± 3.2 mmHg, compared to the middle two quartiles 32 ± 2.3 mmHg, and lower quartile 38.2 ± 4.0 mmHg, (p=0.034). The prevalence of abnormally high pulmonary vascular resistance (>2 standard deviations above the mean) in the high, medium or low VCAM-1 induction groups was 20%, 35% and 80%, respectively (p=0.0066). We also found statistically significant correlations of cell surface VCAM-1 to cardiac output, transpulmonary gradient, pulse pressure, Doppler echocardiography tricuspid regurgitation velocity (TRV) and a marker of systemic iron overload, serum ferritin. Induced cell surface VCAM-1 expression did not correlate significantly in the same subjects with the plasma level of soluble VCAM-1, a previously documented marker associated with high TRV. We found very similar patterns of induction of cell surface expression of P-selectin. These results indicate that the ability of plasma to induce cell surface expression of cell adhesion molecules is a new marker predictive of the diagnosis of catheterization-proven PH in SCD, but it is independent of the levels of the soluble ectodomains of these cell adhesion molecules. These results are consistent with recent publications in the cell adhesion molecule field indicating that independent inflammation-mediated mechanisms regulate adhesion molecule expression and its ectodomain shedding via sheddases. Our findings lead us to speculate that increased sheddase activity may contribute to the high levels of soluble adhesion molecules found in PH, simultaneously reducing the level of cell surface adhesion molecules. Future studies of sheddase activity in SCD PH would help to elucidate this interesting observation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunoelectron microscopic localization of the neural cell adhesion molecules L1 and N-CAM during postnatal development of the mouse cerebellum.

1987 ◽  
Vol 105 (1) ◽  
pp. 569-576 ◽  
Author(s):  
E Persohn ◽  
M Schachner
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Granule Cell ◽  
Cell Adhesion Molecules ◽  
Granule Cells ◽  
Cell Types ◽  
Neural Cell ◽  
Neural Cell Adhesion Molecules ◽  
Neural Cell Adhesion

The cellular and subcellular localization of the neural cell adhesion molecules L1 and N-CAM was studied by pre- and postembedding immunoelectron microscopic labeling procedures in the developing mouse cerebellar cortex. The salient features of the study are: L1 displays a previously unrecognized restricted expression by particular neuronal cell types (i.e., it is expressed by granule cells but not by stellate and basket cells) and by particular subcellular compartments (i.e., it is expressed on axons but not on dendrites or cell bodies of Purkinje cells). L1 is always expressed on fasciculating axons and on postmitotic, premigratory, and migrating granule cells at sites of neuron-neuron contact, but never at contact sites between neuron and glia, thus strengthening the view that L1 is not involved in granule cell migration as a neuron-glia adhesion molecule. While N-CAM antibodies reacting with the three major components of N-CAM (180, 140, and 120 kD) show a rather uniform labeling of all cell types, antibodies to the 180-kD component (N-CAM180) stain only the postmigratory granule cell bodies supporting the notion that N-CAM180, the N-CAM component with the longest cytoplasmic domain, is not expressed before stable cell contacts are formed. Furthermore, N-CAM180 is only transiently expressed on Purkinje cell dendrites. N-CAM is present in synapses on both pre- and post-synaptic membranes. L1 is expressed only preterminally and not in the subsynaptic membranes. These observations indicate an exquisite degree of fine tuning in adhesion molecule expression during neural development and suggest a rich combinatorial repertoire in the specification of cell surface contacts.

TNF-α-induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent

2003 ◽  
Vol 284 (2) ◽  
pp. C422-C428 ◽  
Author(s):  
Makoto Sasaki ◽  
D. Ostanin ◽  
J. W. Elrod ◽  
T. Oshima ◽  
P. Jordan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Nadph Oxidase ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Tnf Α ◽  
Oxidase Inhibition ◽  
Endothelial Adhesion Molecules ◽  
Cytochrome P 450

It is strongly suspected that cytokine-induced gene expression in inflammation is oxidant mediated; however, the intracellular sources of signaling oxidants remain controversial. In inflammatory bowel disease (IBD) proinflammatory cytokines, such as TNF-α, trigger gene expression of endothelial adhesion molecules including mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 plays an essential role in gut inflammation by governing the infiltration of leukocytes into the intestine. Several groups suggest that endothelial-derived reduced NADP (NADPH) oxidase produces signaling oxidants that control the expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1). In addition to NADPH oxidase, cytochrome P-450 (CYP450) monooxygenases have also been shown to trigger cytokine responses. We found that in high endothelial venular cells (SVEC4-10), multiple inhibitors of CYP450 monooxygenases (SKF-525a, ketoconazole, troleandomycin, itraconazole) attenuated TNF-α induction of MAdCAM-1, whereas NADPH oxidase inhibition (PR-39) did not. Conversely, E-selectin, ICAM-1, and VCAM-1 induction requires both NADPH oxidase and CYP450-derived oxidants. We show here that MAdCAM-1 induction may depend exclusively on CYP450-derived oxidants, suggesting that CYP450 blockers might represent a possible novel therapeutic treatment for human IBD.

scholarly journals Functional N-methyl-D-aspartate receptors in O-2A glial precursor cells: a critical role in regulating polysialic acid-neural cell adhesion molecule expression and cell migration.

1996 ◽  
Vol 135 (6) ◽  
pp. 1565-1581 ◽  
Author(s):  
C Wang ◽  
W F Pralong ◽  
M F Schulz ◽  
G Rougon ◽  
J M Aubry ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Nmda Receptor ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Polysialic Acid ◽  
Neural Cell ◽  
Adhesion Molecule Expression ◽  
Neural Cell Adhesion

The capacity for long-distance migration of the oligodendrocyte precursor cell, oligodendrocyte-type 2 astrocyte (O-2A), is essential for myelin formation. To study the molecular mechanisms that control this process, we used an in vitro migration assay that uses neurohypophysial explants. We provide evidence that O-2A cells in these preparations express functional N-methyl-D-aspartate (NMDA) receptors, most likely as homomeric complexes of the NR1 subunit. We show that NMDA evokes an increase in cytosolic Ca2+ that can be blocked by the NMDA receptor antagonist AP-5 and by Mg2+. Blocking the activity of these receptors dramatically diminished O-2A cell migration from explants. We also show that NMDA receptor activity is necessary for the expression by O-2A cells of the highly sialylated polysialic acid-neural cell adhesion molecule (PSA-NCAM) that is required for their migration. Thus, glutamate or glutamate receptor ligands may regulate O-2A cell migration by modulating expression of PSA-NCAM. These studies demonstrate how interactions between ionotropic receptors, intracellular signaling, and cell adhesion molecule expression influence cell surface properties, which in turn are critical determinants of cell migration.

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