Characterization of an antiglycoprotein Ib monoclonal antibody that specifically inhibits platelet-thrombin interaction.
Platelet glycoprotein Ib (GPIb) acts as a high-affinity thrombin binding site and as a receptor for von Willebrand Factor (vWF). A new anti-GPIb monoclonal antibody (mAB) VM16d was produced that specifically inhibited platelet-thrombin but not platelet-vWF interaction. The epitope for VM16d was located within the 45 kDa N-terminal region of the alpha-chain of GPIb. VM16d inhibited platelet aggregation induced by low dose thrombin (0.05 U/ml) but did not affect platelet aggregation induced by ristocetin, bovine vWF, ADP or collagen. The same inhibitory effects on thrombin-induced platelet aggregation were observed with the whole IgG molecule of VM16d and its F(ab')2 and F(ab') fragments. VM16d also inhibited 14C-serotonin secretion induced by low dose thrombin and binding of 125I-thrombin but not ristocetin-dependent binding of 125I-vWF to platelets. These data indicate that the high-affinity thrombin binding site is located on the N-terminal 45 kDa domain of GPIb and that it is topographically separated from the vWF binding site.
Mazurov
A V
AV
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, USSR.
Vinogradov
D V
DV
Vlasik
T N
TN
Repin
V S
VS
Booth
W J
WJ
Berndt
M C
MC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D018179:Receptors, Thrombin; D012310:Ristocetin / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor; D012310:Ristocetin; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin