Linked Life Data

12724354

Source:http://linkedlifedata.com/resource/pubmed/id/12724354

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 12
pubmed:dateCreated
2003-5-26
pubmed:abstractText
Cell-surface annexin 2 (A2) and its ligand p11 have been implicated in fibrinolysis because of their ability to accelerate tissue plasminogen activator (tPA)-mediated activation of plasminogen to plasmin. Because thrombin is a potent cell modulator obligately produced at the site of clot formation, we hypothesized that the amount of cell-surface A2 and p11 might be altered by thrombin with consequent effects on plasmin generation. In support of this hypothesis, immunofluorescence microscopy and hydrophilic biotinylation experiments showed that both A2 and p11 were significantly increased on the surface of human umbilical vein endothelial cells (HUVECs) treated with thrombin (0.8-8 nM) for 5 minutes followed by 1 hour at 37 degrees C. Intracellular immunofluorescence microscopy and immunoblot analyses of whole cell extracts revealed increased p11 but unchanged A2 in response to thrombin, suggesting that transbilayer trafficking of A2 might be controlled by p11. The thrombin receptor-activating peptide (TRAP) similarly affected cells, demonstrating that cell signaling at least involved the type-1 protease activated receptor (PAR-1). An effect on the fibrinolysis pathway after treatment of HUVECs with thrombin was shown by increased fluorescein-labeled plasminogen binding to cells, which was inhibited by an antibody specific for p11. This was confirmed by observing that thrombin pretreatment of HUVECs increased biotin-modified plasminogen binding. Utilizing a chromogenic assay, pretreatment of HUVECs by thrombin further enhanced activation of the Glu and Lys forms of plasminogen by tPA. These data suggest a novel mechanism that links the coagulation and fibrinolysis pathways by thrombin-mediated feedback.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2399-408
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12724354-Annexin A2, pubmed-meshheading:12724354-Antibodies, pubmed-meshheading:12724354-Blood Coagulation, pubmed-meshheading:12724354-Cells, Cultured, pubmed-meshheading:12724354-Endothelium, Vascular, pubmed-meshheading:12724354-Fibrinolysis, pubmed-meshheading:12724354-Fluorescent Antibody Technique, pubmed-meshheading:12724354-Humans, pubmed-meshheading:12724354-Plasminogen, pubmed-meshheading:12724354-Protein Binding, pubmed-meshheading:12724354-Protein Transport, pubmed-meshheading:12724354-Receptor, PAR-1, pubmed-meshheading:12724354-Receptors, Cell Surface, pubmed-meshheading:12724354-Receptors, Thrombin, pubmed-meshheading:12724354-S100 Proteins, pubmed-meshheading:12724354-Thrombin, pubmed-meshheading:12724354-Tissue Plasminogen Activator, pubmed-meshheading:12724354-Up-Regulation
pubmed:year
2003
pubmed:articleTitle
Thrombin induces endothelial cell-surface exposure of the plasminogen receptor annexin 2.
pubmed:affiliation
Canadian Blood Services, R&D Department, 1800 Alta Vista Drive, Ottawa, ON K1G 4J5, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't