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Title: Binding properties of monoclonal antibodies against human fragment D-dimer of cross-linked fibrin to human plasma clots in an in vivo model in rabbits
Authors: Holvoet, Paul ×
Stassen, Jean-Marie
Hashimoto, Y
Spriggs, D
Devos, P
Collen, Desire #
Issue Date: Apr-1989
Series Title: Thrombosis and haemostasis vol:61 issue:2 pages:307-13
Abstract: Two (MA-15C5 and MA-8D3) out of approximately 500 monoclonal antibodies, obtained by fusion of P3X63-Ag8-6.5.3 myeloma cells with spleen cells of mice immunized with purified fragment D-dimer from human fibrin, demonstrated a more than 1,000-fold higher affinity for fragment D-dimer than for native fibrinogen. MA-15C5 was directed against a neoantigenic determinant only expressed in fragment D-dimer. MA-8D3 reacted equally well with fragment D-dimer of crosslinked fibrin and with fragment D of non-crosslinked fibrin but not with fragment D of fibrinogen. Both monoclonal antibodies did not crossreact with rabbit fibrin and its degradation products. The binding of 125I-labeled Fab fragments to human plasma clots, introduced and aged for 1 hr in the jugular vein of heparinized rabbits was studied. Following injection of an equimolar mixture of Fab fragments derived from MA-15C5 and MA-8D3, the clot to blood ratios of radioactivity increased from 3.2 +/- 1.2 (mean +/- SD) at 4 hr to 7.2 +/- 1.4 at 17 hr. The binding of Fab fragments of MA-15C5 and MA-8D3 was independent of the age (1 to 72 hrs) of the clot and of heparin anticoagulation and was only slightly decreased (by 20%) in the presence of circulating human fibrinogen (90 mg/kg body weight) and of human cross-linked fibrin degradation products at a plasma concentration of 10 micrograms/ml. The binding of Fab fragments of MA-15C5 and MA-8D3 to occlusive human plasma clots in the femoral artery of rabbits was comparable to that of the non-occlusive human plasma clots in the jugular vein.(ABSTRACT TRUNCATED AT 250 WORDS)
ISSN: 0340-6245
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Atherosclerosis and Metabolism (-)
Molecular and Vascular Biology
× corresponding author
# (joint) last author

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