scholarly journals Polysialylation of the Synaptic Cell Adhesion Molecule 1 (SynCAM 1) Depends Exclusively on the Polysialyltransferase ST8SiaII in Vivo

2012 ◽  
Vol 287 (42) ◽  
pp. 35170-35180 ◽  
Author(s):  
Manuela Rollenhagen ◽  
Sarah Kuckuck ◽  
Christina Ulm ◽  
Maike Hartmann ◽  
Sebastian P. Galuska ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Polysialic Acid ◽  
Cryptic Exon ◽  
Carbohydrate Polymer ◽  
Cell Type Specific ◽  
Developing Mouse Brain ◽  
Cell Adhesion Molecule 1

Polysialic acid is a unique carbohydrate polymer specifically attached to a limited number of glycoproteins. Among them is synaptic cell adhesion molecule 1 (SynCAM 1), a member of the immunoglobulin (Ig) superfamily composed of three extracellular Ig-like domains. Polysialylation of SynCAM 1 is cell type-specific and was exclusively found in NG2 cells, a class of multifunctional progenitor cells that form specialized synapses with neurons. Here, we studied the molecular requirements for SynCAM 1 polysialylation. Analysis of mice lacking one of the two polysialyltransferases, ST8SiaII or ST8SiaIV, revealed that polysialylation of SynCAM 1 is exclusively mediated by ST8SiaII throughout postnatal brain development. Alternative splicing of the three variable exons 8a, 8b, and 8c can theoretically give rise to eight transmembrane isoforms of SynCAM 1. We detected seven transcript variants in the developing mouse brain, including three variants containing exon 8c, which was so far regarded as a cryptic exon in mice. Polysialylation of SynCAM 1 was restricted to four isoforms in perinatal brain. However, cell culture experiments demonstrated that all transmembrane isoforms of SynCAM 1 can be polysialylated by ST8SiaII. Moreover, analysis of domain deletion constructs revealed that Ig1, which harbors the polysialylation site, is not sufficient as an acceptor for ST8SiaII. The minimal polypeptide required for polysialylation contained Ig1 and Ig2, suggesting an important role for Ig2 as a docking site for ST8SiaII.

Airway recruitment of leukocytes in mice is dependent on alpha4-integrins and vascular cell adhesion molecule-1

1997 ◽  
Vol 272 (2) ◽  
pp. L219-L229 ◽  
Author(s):  
J. E. Chin ◽  
C. A. Hatfield ◽  
G. E. Winterrowd ◽  
J. R. Brashler ◽  
S. L. Vonderfecht ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Pulmonary Inflammation ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

The involvement of the alpha4-integrin very late activation antigen 4 and vascular cell adhesion molecule-1 (VCAM-1) in leukocyte trafficking into the airways of ovalbumin (OA)-sensitized and OA-challenged mice was investigated using in vivo administration of anti-alpha4 monoclonal antibodies (mAb) PS/2, R1-2, and M/K-2.7 (MK2), specific for VCAM-1. VCAM-1 was upregulated on endothelial cells in lung tissue after OA inhalation. PS/2, R1-2, or MK2 significantly inhibited the recruitment of eosinophils and lymphocytes into the bronchoalveolar lavage (BAL) fluid and decreased inflammation in the lung tissues. Escalating in vivo doses of PS/2 or MK2 increased circulating levels of rat immunoglobulin G in the plasma. The binding of phycoerytherin-labeled anti-alpha4 mAb to blood T cells from PS/2-treated mice was reduced, implying that alpha4 sites were already occupied. T cells and eosinophils in BAL fluid from mice treated with PS/2 or MK2 were phenotypically different from controls. Selective decreases of alpha4+ T cells in the BAL fluid after PS/2 or MK2 treatment were coupled with changes in CD8+, CD11a, and CD62L expression. The alpha4-integrin and VCAM-1 may have important roles in the antigen-induced recruitment of T cells and eosinophils during OA-induced airway inflammation. The data suggest that these adhesion molecules may be suitable targets for therapeutic intervention in certain conditions of pulmonary inflammation.

Platelet-derived microparticles from recurrent miscarriage associated with antiphospholipid antibody syndrome influence behaviours of trophoblast and endothelial cells

2019 ◽  
Vol 25 (8) ◽  
pp. 483-494 ◽  
Author(s):  
Qian Zhou ◽  
Yan Lian ◽  
Yan Zhang ◽  
Lei Li ◽  
Hongyan Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Recurrent Miscarriage ◽  
Umbilical Vein ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Invasion And Migration ◽  
Cell Adhesion Molecule 1

AbstractPlatelet-derived microparticles (PMPs) are a type of microparticle budding from platelets undergoing activation or apoptosis in many autoimmune diseases, including antiphospholipid antibody syndrome (APS). PMPs may also contribute to recurrent miscarriage, although the exact mechanism is unclear. The aim of this study was to determine the potential biological mechanism by which abnormal PMP activation may affect recurrent miscarriage. PMPs were counted by fluorescence-activated cell sorting (FACS) and compared between the healthy control (HC) and recurrent miscarriage/APS groups. Different effects of PMPs isolated by FACS from patients with recurrent miscarriage/APS and HCs were explored. Capillary electrophoresis immunoquantification, RT-qPCR, Luminex xMAP and immunofluorescence staining were performed to investigate all these different effects of PMPs. We found that the difference in the counts of PMP was not significant. However the expression of the inflammatory cytokine tumour necrosis factor-α (TNF-α) and the adhesion molecules intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were increased by PMPs derived from the recurrent miscarriage/APS group. PMPs isolated from patients with recurrent miscarriage/APS also more potently stimulated monocyte recruitment, inhibited angiogenesis and promoted human umbilical vein endothelial cell (HUVEC) apoptosis, in comparison to PMPs from HCs matched for gestational week. Moreover, PMPs could be ternalized by HTR-8/SVneo cells and could increase apoptosis of these cells and decrease trophoblastic invasion and migration. To supplement our work, the limited sample size needs to be increased, and further in-vivo work is necessary. Findings from this study indicate that abnormal activation of PMPs contributes to recurrent miscarriage/APS progression and provides potential therapeutic targets.

scholarly journals D-4F Ameliorates Contrast Media–Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Yansong Guo ◽  
Wei Li ◽  
Mingming Qian ◽  
Ting Jiang ◽  
Ping Guo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Contrast Media ◽  
Cell Viability ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Ros Production ◽  
Cell Adhesion Molecule 1

Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregulating heme oxygenase-1 (HO-1) expression and scavenging excessively generated reactive oxygen species (ROS). However, whether D-4F could ameliorate oxidative injuries in endothelial cells through suppressing ROS production remains unclear. In this study, a representative nonionic iodinated CM, iodixanol, was chosen for the in vitro and in vivo studies. Endothelial cell viability was assayed using micrographs, lactate dehydrogenase (LDH) activity, and cell counting kit-8 (CCK-8). Apoptosis was detected using flow cytometry analysis and caspase-3 activation. Endothelial inflammation was tested using monocyte adhesion assay and adhesion molecule expression. ROS production was detected by measuring the formation of lipid peroxidation malondialdehyde (MDA) through the thiobarbituric acid reactive substance (TBARS) assay. Peroxynitrite (ONOO⁻) formation was tested using the 3-nitrotyrosine ELISA kit. Iodixanol impaired cell viability, promoted vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression, and induced cell apoptosis in human umbilical vein endothelial cells (HUVECs). However, D-4F mitigated these injuries. Furthermore, iodixanol induced the phosphorylation of protein kinase C (PKC) beta II, p47, Rac1, and endothelial nitric oxide synthase (eNOS) at Thr495, which elicited ROS release and ONOO⁻ generation. D-4F inhibited NADPH oxidase (NOX) activation, ROS production, and ONOO⁻ formation via the AMP-activated protein kinase (AMPK)/PKC pathway. Additionally, after an intravascular injection of iodixanol in Sprague Dawley rats, iodixanol induced a remarkable inflammatory response in arterial endothelial cells, although significant apoptosis and morphological changes were not observed. D-4F alleviated the vessel inflammation resulting from iodixanol in vivo. Collectively, besides scavenging ROS, D-4F could also suppress ROS production and ONOO⁻ formation through the AMPK/PKC pathway, which ameliorated oxidative injuries in endothelial cells. Hence, D-4F might serve as a potential agent in preventing CI-AKI.

scholarly journals NOX2 in lung inflammation: quantum dot based in situ imaging of NOX2-mediated expression of vascular cell adhesion molecule-1

2014 ◽  
Vol 306 (3) ◽  
pp. L260-L268 ◽  
Author(s):  
Rebecca L. Orndorff ◽  
Nankang Hong ◽  
Kevin Yu ◽  
Sheldon I. Feinstein ◽  
Blaine J. Zern ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Quantum Dot ◽  
Adhesion Molecule ◽  
Lung Inflammation ◽  
Cell Adhesion Molecule ◽  
Immune Cell ◽  
Pulmonary Inflammation ◽  
Vascular Endothelial Cell ◽  
Cell Adhesion Molecule 1

Quantum dot (QD) imaging is a powerful tool for studying signaling pathways as they occur. Here we employ this tool to study adhesion molecule expression with lung inflammation in vivo. A key event in pulmonary inflammation is the regulation of vascular endothelial cell adhesion molecule-1 (VCAM), which drives activated immune cell adherence. The induction of VCAM expression is known to be associated with reactive oxygen species (ROS) production, but the exact mechanism or the cellular source of ROS that regulates VCAM in inflamed lungs is not known. NADPH oxidase 2 (NOX2) has been reported to be a major source of ROS with pulmonary inflammation. NOX2 is expressed by both endothelial and immune cells. Here we use VCAM-targeted QDs in a mouse model to show that NOX2, specifically endothelial NOX2, induces VCAM expression with lung inflammation in vivo.

scholarly journals Rat Neutrophils Express α4 and β1 Integrins and Bind to Vascular Cell Adhesion Molecule-1 (VCAM-1) and Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1)

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2341-2346 ◽  
Author(s):  
Kelly L. Davenpeck ◽  
Sherry A. Sterbinsky ◽  
Bruce S. Bochner
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Flow Cytometric Analysis ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Β1 Integrins ◽  
Cell Adhesion Molecule 1

Abstract The α4 integrins, which are constitutively expressed on all human leukocyte subtypes except neutrophils, interact with vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule (MAdCAM-1) on endothelium to mediate selective recruitment of leukocyte subpopulations, other than neutrophils, to sites of inflammation. However, here we report that a different paradigm of leukocyte recruitment may exist in the rat. Flow cytometric analysis of rat neutrophils using a panel of monoclonal antibodies which recognize rat α4 and β1 integrins showed consistent, low levels of expression. Although α4 was expressed at lower levels on neutrophils than all other rat leukocytes, this level of expression was sufficient to mediate significant levels of α4- and β1-dependent neutrophil adhesion to rat and human VCAM-1, and α4-dependent, but β1-independent, adhesion to human MAdCAM-1. These data suggest that rat neutrophils, unlike other species, may use α4 integrins to traffic to sites of inflammation in vivo.

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