Effects of an antifibrin monoclonal antibody and fragments thereof on some properties of fibrin.
Antifibrin monoclonal antibody Y22, of IgG1-subclass, has its epitope in the D-domain of fibrin. In a thrombin time assay, Y22 and its F(ab)2 fragments interfere with clotting of citrated plasma. Transmission and scanning electronmicroscopic studies show that clotting of citrated blood or plasma in the presence of Y22 results in formation of thin, short fibrin fibres. The (smaller) Fab fragments of Y22 did not have an anti-clotting effect. This suggests that the anticoagulant effect of Y22 is due to steric hindrance of the association of fibrin monomers. A control antibody and its F(ab)2 and Fab fragments have no effect on fibrin formation. In a parabolic rate assay, Y22 Fab fragments interfered strongly with the fibrin-induced enhancement of the t-PA-catalyzed plasminogen activation, whereas intact Y22 and a control antibody did not. In contrast with their effects on the fibrin assembly, the effects of Y22, Y22-F(ab)2 and Y22-Fab on the capacity of fibrin to act as a rate-enhancer in the plasminogen activation by t-PA appears to decrease with the size of the immunoreactive entity. As is discussed, this may be due to the differential accessibility of sites involved in stimulation and polymerization which are located in the fibrin D-domain.
Wasser
M N
MN
Gaubius Institute TNO, Leiden, The Netherlands.
Welling
M
M
Lamers
G
G
Pauwels
E K
EK
Nieuwenhuizen
W
W
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002384:Catalysis; D005337:Fibrin / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000378:metabolism; D013918:Thrombin Time; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D005337:Fibrin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator