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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0007577,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0026336,
umls-concept:C0085243,
umls-concept:C0162768,
umls-concept:C0205734,
umls-concept:C0376518,
umls-concept:C0597357,
umls-concept:C1515655,
umls-concept:C1521840,
umls-concept:C1801960,
umls-concept:C1879547,
umls-concept:C2003941
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pubmed:issue |
2
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pubmed:dateCreated |
1995-8-16
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pubmed:abstractText |
The alpha 4 beta 1-integrin (CD49d, CD29) constitutively expressed on leukocytes regulates cell migration to inflammatory sites, cell activation, and development through its interactions with two alternate ligands, vascular cell adhesion molecule-1 (VCAM-1; CD106) expressed on cytokine-activated endothelium, dendritic and stromal cells, and the extracellular matrix protein fibronectin. Another alpha 4-integrin receptor, alpha 4 beta 7, expressed on leukocytes also binds VCAM-1 and fibronectin (FN), and controls homing to mucosal tissues through its interactions with mucosal vascular addressin MAdCAM-1. In vitro studies have shown that alpha 4-dependent cell adhesion is regulated by the activation state of the cell and by divalent cations. However, the existence and role of cells with different alpha 4 activation states in vivo have not been defined. Herein we show that a soluble ligand with the two N-terminal domains of human VCAM-1 fused to a human IgG1 constant region, VCAM-Ig, binds selectively to activated alpha 4-receptors on murine cells, such as those induced by Mn2+ in vitro. To determine whether the cells identified by VCAM-Ig were required under physiologic conditions, we assessed its anti-inflammatory effect. We show that VCAM-Ig is not bound to the majority of murine alpha 4+ cells after in vivo administration, yet it significantly delays the onset of adoptively transferred autoimmune diabetes. Thus, soluble VCAM-Ig can modify alpha 4-dependent disease progression, apparently by its selective action on cells with activated alpha 4-integrin receptors, thereby providing evidence for distinct alpha 4 activation states in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4,
http://linkedlifedata.com/resource/pubmed/chemical/Manganese,
http://linkedlifedata.com/resource/pubmed/chemical/Methotrexate,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Very Late Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
155
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
938-46
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:7608569-Animals,
pubmed-meshheading:7608569-Antigens, CD,
pubmed-meshheading:7608569-Autoimmune Diseases,
pubmed-meshheading:7608569-Diabetes Mellitus, Type 1,
pubmed-meshheading:7608569-Female,
pubmed-meshheading:7608569-Immunoglobulins,
pubmed-meshheading:7608569-Immunotherapy, Adoptive,
pubmed-meshheading:7608569-Integrin alpha4,
pubmed-meshheading:7608569-Islets of Langerhans,
pubmed-meshheading:7608569-Lymphocyte Depletion,
pubmed-meshheading:7608569-Manganese,
pubmed-meshheading:7608569-Methotrexate,
pubmed-meshheading:7608569-Mice,
pubmed-meshheading:7608569-Mice, Inbred NOD,
pubmed-meshheading:7608569-Receptors, Very Late Antigen,
pubmed-meshheading:7608569-Recombinant Fusion Proteins,
pubmed-meshheading:7608569-Vascular Cell Adhesion Molecule-1
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pubmed:year |
1995
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pubmed:articleTitle |
Vascular cell adhesion molecule-Ig fusion protein selectively targets activated alpha 4-integrin receptors in vivo. Inhibition of autoimmune diabetes in an adoptive transfer model in nonobese diabetic mice.
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pubmed:affiliation |
Biogen, Inc., Cambridge, MA 02142, USA.
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pubmed:publicationType |
Journal Article
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