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Titolo:
Characterisation, cloning and sequencing of a conformation-dependent monoclonal antibody to the alpha(IIb)beta(3) integrin: interest for use in thrombus detection
Autore:
Dabadie, M; Valli, N; Jacobin, MJE; Laroche-Traineau, J; Barat, JL; Ducassou, D; Nurden, AT; Clofent-Sanchez, G;
Indirizzi:
Univ Bordeaux 2, Biophys Lab, Equipe Imagerie Med EA 1669, F-33076 Bordeaux, France Univ Bordeaux 2 Bordeaux France F-33076 A 1669, F-33076 Bordeaux, France Hop Cardiol, CNRS, UMR 5533, F-33604 Pessac, France Hop Cardiol Pessac France F-33604 CNRS, UMR 5533, F-33604 Pessac, France GISIR, Ctr Vie Condorcet, F-33608 Pessac, France GISIR Pessac France F-33608 R, Ctr Vie Condorcet, F-33608 Pessac, France
Titolo Testata:
PLATELETS
fascicolo: 7, volume: 12, anno: 2001,
pagine: 395 - 405
SICI:
0953-7104(200111)12:7<395:CCASOA>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
IIB-IIIA COMPLEX; PLATELET GLYCOPROTEIN-IIIA; ACTIVATED PLATELETS; PROTEOLYTIC CLEAVAGE; FIBRINOGEN RECEPTOR; BINDING; ANTAGONISTS; GPIIB/IIIA; PEPTIDES; MYOSIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Dabadie, M Univ Bordeaux 2, Biophys Lab, Equipe Imagerie Med EA 1669, 146 Rue Leo Saignat, F-33076 Bordeaux, France Univ Bordeaux 2 146 Rue Leo Saignat Bordeaux France F-33076 ce
Citazione:
M. Dabadie et al., "Characterisation, cloning and sequencing of a conformation-dependent monoclonal antibody to the alpha(IIb)beta(3) integrin: interest for use in thrombus detection", PLATELETS, 12(7), 2001, pp. 395-405

Abstract

The detection of newly formed thrombi is of primary importance in clinicalmedicine. The activated platelet is a potential target for the localization of thrombotic lesions in arteries. The integrin alpha (IIb)beta (3) in the platelet membrane changes conformation upon activation. A novel anti-alpha (IIb)beta (3) monoclonal antibody (MAb), XIIF9, is described which recognizes an epitope whose expression was enhanced by activation. RadioiodinatedXIIF9 bound to a single class of sites on the beta (3) subunit, with 13600+/- 2000 molecules bound per unstimulated platelet and a K-d of 34.5 nM. Platelets stimulated with 0.5 U/ml of thrombin bound 66000 +/- 4000 molecules/cell (K-d = 51.6 nM). Moreover, XIIF9 binding to unstimulated platelets could be increased 4-fold by treatment of the alpha (IIb)beta (3) complex with 5 mM EDTA. Thus, XIIF9 recognized an epitope on the beta (3) subunit whose accessibility was increased upon thrombin activation or EDTA treatment. Sequence analysis of the gene segment encoding the XIIF9 heavy chain revealed interesting motifs shared with cyclic CX6-7C anti-alpha (IIb)beta (3) peptides or with AC7, a published MAb specific for activated alpha (IIb)beta (3). In vivo experiments in atherosclerotic rabbits followed by immunohistological analysis, revealed a specific binding of XIIF9 on platelets engagedin thrombus formation, demonstrating real clinical potential for such MAbsin imaging.

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Documento generato il 05/12/20 alle ore 00:16:04