Linked Life Data

10887113

Source:http://linkedlifedata.com/resource/pubmed/id/10887113

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-17
pubmed:abstractText
Proteolytic cleavage of single-chain high molecular weight kininogen (HK) by kallikrein releases the short-lived vasodilator bradykinin and leaves behind 2-chain high molecular weight kininogen (HKa) that has been previously reported to exert antiadhesive properties as well as to bind to the urokinase receptor (uPAR) on endothelial cells. In this study we defined the molecular mechanisms for the antiadhesive effects of HKa related to disruption of integrin- and uPAR-mediated cellular interactions. Vitronectin (VN) but not fibrinogen or fibronectin-dependent alphavbeta(3) integrin-mediated adhesion of endothelial cells was blocked by HKa or its isolated domain 5. In a purified system, HKa but not HK competed for the interaction of VN with alphavbeta(3) integrin, because HKa and the isolated domain 5 but not HK bound to both multimeric and native VN in a Zn(2+)-dependent manner. The interaction between HKa or domain 5 with VN was prevented by heparin, plasminogen activator inhibitor-1, and a recombinant glutathione-S-transferase (GST)-fusion peptide GST-VN (1-77) consisting of the amino terminal portion of VN (amino acids 1-77), but not by a cyclic arginyl-glycyl-aspartyl peptide, indicating that HKa interacts with the amino terminal portion of VN ("somatomedin B region"). Furthermore, we have confirmed that HKa but not HK bound to uPAR and to the truncated 2-domain form of uPAR lacking domain 1 in a Zn(2+)-dependent manner. Through these interactions, HKa or its recombinant His-Gly-Lys-rich domain 5 completely inhibited the uPAR-dependent adhesion of myelomonocytic U937 cells and uPAR-transfected BAF-3 cells to VN and thereby promoted cell detachment. By immunogold electron microscopy, both VN and HK/HKa were found to be colocalized in sections from human atherosclerotic coronary artery, indicating that the described interactions are likely to take place in vivo. Taken together, HK and HKa inhibit different VN-responsive adhesion receptor systems and may thereby influence endothelial cell- or leukocyte-related interactions in the vasculature, particularly under inflammatory conditions. (Blood. 2000;96:514-522)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
514-22
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10887113-Arteriosclerosis, pubmed-meshheading:10887113-Cell Adhesion, pubmed-meshheading:10887113-Endothelium, Vascular, pubmed-meshheading:10887113-Fibrinogen, pubmed-meshheading:10887113-Humans, pubmed-meshheading:10887113-Kininogens, pubmed-meshheading:10887113-Leukocytes, pubmed-meshheading:10887113-Molecular Weight, pubmed-meshheading:10887113-Monocytes, pubmed-meshheading:10887113-Osteosarcoma, pubmed-meshheading:10887113-Plasminogen Activator Inhibitor 1, pubmed-meshheading:10887113-Receptors, Cell Surface, pubmed-meshheading:10887113-Receptors, Urokinase Plasminogen Activator, pubmed-meshheading:10887113-Receptors, Vitronectin, pubmed-meshheading:10887113-Tumor Cells, Cultured, pubmed-meshheading:10887113-U937 Cells, pubmed-meshheading:10887113-Vitronectin, pubmed-meshheading:10887113-Zinc
pubmed:year
2000
pubmed:articleTitle
Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor-dependent interactions.
pubmed:affiliation
Institute for Biochemistry and the Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't