Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-10-24
pubmed:abstractText
The detection of newly formed thrombi is of primary importance in clinical medicine. The activated platelet is a potential target for the localization of thrombotic lesions in arteries. The integrin alpha(IIb)beta(3) 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. Radioiodinated XIIF9 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 engaged in thrombus formation, demonstrating real clinical potential for such MAbs in imaging.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0953-7104
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
395-405
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11674856-Amino Acid Motifs, pubmed-meshheading:11674856-Amino Acid Sequence, pubmed-meshheading:11674856-Animals, pubmed-meshheading:11674856-Antibodies, Monoclonal, pubmed-meshheading:11674856-Antibody Affinity, pubmed-meshheading:11674856-Antibody Specificity, pubmed-meshheading:11674856-Binding Sites, pubmed-meshheading:11674856-Cloning, Molecular, pubmed-meshheading:11674856-Disease Models, Animal, pubmed-meshheading:11674856-Edetic Acid, pubmed-meshheading:11674856-Immunoconjugates, pubmed-meshheading:11674856-Iodine Radioisotopes, pubmed-meshheading:11674856-Male, pubmed-meshheading:11674856-Molecular Sequence Data, pubmed-meshheading:11674856-Platelet Activation, pubmed-meshheading:11674856-Platelet Glycoprotein GPIIb-IIIa Complex, pubmed-meshheading:11674856-Protein Conformation, pubmed-meshheading:11674856-Rabbits, pubmed-meshheading:11674856-Sequence Analysis, pubmed-meshheading:11674856-Thrombin, pubmed-meshheading:11674856-Thrombosis
pubmed:year
2001
pubmed:articleTitle
Characterisation, cloning and sequencing of a conformation-dependent monoclonal antibody to the alphaIIbbeta3 integrin: interest for use in thrombus detection.
pubmed:affiliation
Equipe Imagerie Médical EA 1699, Laboratoire de Biophysique, Université de Bordeaux II, 146 Rue Léo-Saignat, 33076 Bordeaux, France. michele.dabadie@u-bordeaux2.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't