Abstract:
:We have investigated the effect of a new Leu196Pro mutation, identified in the MIDAS-like domain of the beta3 integrin subunit in a patient with type II Glanzmann thrombasthenia, on beta3 integrin receptor function. Expression of the mutant beta3Pro196 subunit in CHO cells, either associated with recombinant human alphaIIb or alphav, resulted in normal biosynthesis of beta3 and heterodimerization with alphav or alphaIIb, but selectively interfered with alphaIIbbeta3 maturation and transport to the cell surface. Functional analysis of the beta3 mutant receptors revealed strong inhibition of alphavbeta3-mediated cell spreading on immobilized fibrinogen, focal contact formation, p125FAK phosphorylation and fibrin clot retraction, as opposed to normal alphaIIbbeta3-mediated cell interaction with immobilized fibrinogen, focal contact translocation and signaling. In contrast, antibody- or DTT-activated mutant aIIbbeta3 was unable to bind soluble fibrinogen or the ligand mimetic PAC-1 monoclonal antibody, but underwent a conformational change following RGD peptide binding as demonstrated by AP5-LIBS epitope expression. These results suggest that (1) the highly conserved TL196T motif in the beta3 integrin subunit is located in a domain structurally important for the exposure of a functional binding site for soluble fibrinogen; and (2) that the MIDAS-like contact site in beta3 is not involved in alphaIIbbeta3-mediated cell adhesion to immobilized fibrinogen, while it is essential for alphavbeta3-mediated interaction with this ligand.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Morel-Kopp MC,Melchior C,Chen P,Ammerlaan W,Lecompte T,Kaplan C,Kieffer Nkeywords:
subject
Has Abstractpub_date
2001-12-01 00:00:00pages
1425-34issue
6eissn
0340-6245issn
2567-689Xpii
01121425journal_volume
86pub_type
杂志文章abstract::We investigated the influence of low molecular weight dextran sulfate (LMWdxs) and low molecular weight heparins (LMWH: dalteparin, enoxaparin and nadroparin) on the inhibition of FXIa by C1-inhibitor, alpha1-antitrypsin, alpha2-antiplasmin and antithrombin in a purified system and in plasma. The second order rate con...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-06-0438
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::Sulodexide, a highly purified glycosaminoglycan, was investigated for treatment of venous leg ulcers. Patients (n = 235) undergoing local treatment including wound care and compression bandaging, were randomised to receive either sulodexide or matching placebo for three months. Primary study endpoint was complete ulce...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:2002-06-01 00:00:00
abstract::Thrombomodulin (TM), a marker of endothelial cell damage, has been localized to the placental syncytiotrophoblast. A prospective cohort study of twenty-five pregnant women who were admitted with a clinical diagnosis of placental abruption was undertaken. Abruption was confirmed after delivery in eight cases (Group 1)....
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-09-0615
更新日期:2011-03-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析,评审
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更新日期:2015-02-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-12-29 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-02-0106
更新日期:2003-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-07-0454
更新日期:2010-03-01 00:00:00
abstract::Primary immune thrombocytopaenia (ITP) is the most common haemorrhagic disease. Although most patients respond initially to mainstream therapies, such as corticosteroids, immunosuppressants or rituximab, a large proportion of patients fail to respond or relapse. These treatments only affect B lymphocytes or short-live...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1669921
更新日期:2018-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-11-0895
更新日期:2017-04-27 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-02-0118
更新日期:2004-07-01 00:00:00
abstract::The mechanisms or host factors involved in septic thrombus or vegetation formation in Staphylococcus aureus-induced infective endocarditis (IE) are unclear. Using an experimental endocarditis rat model, here we demonstrated that S. aureus HG001-induced vegetation was composed of bacterial floes encased in aggregated p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-1678665
更新日期:2019-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-09-0646
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-02-18 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-12-0778
更新日期:2011-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-10-22 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-02-0106
更新日期:2005-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-12-22 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::Congenital afibrinogenemia and severe hypofibrinogenemia are severe bleeding disorders characterized by either undetectable or very low levels of fibrinogen in patients' plasma and platelets. A majority of the reported cases are caused by mutations in the fibrinogen Aalpha chain. In this study, we identified a genetic...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH06-01-0020
更新日期:2006-06-01 00:00:00
abstract::Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and is considered as an attractive drug target. We generated two different antibody fragments, an antigen-binding fragment (Fab) and a single-chain variable fragment (scFv), derived from three distinct monoclonal antibodies (MAs) that inhibit t...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH08-09-0834
更新日期:2009-07-01 00:00:00