The effect of peptides and monoclonal antibodies that bind to platelet glycoprotein IIb-IIIa complex on the development of clot tension.
The development of tension in platelet-rich clots is a manifestation of fibrin polymer binding to platelets as well as platelet contractile activity. Arg-Gly-Asp(RGD)-containing peptides of fibrinogen alpha-chain and gamma-400-411 of fibrinogen gamma chain increased clot tension considerably, especially when it developed under isometric conditions. Morphometry revealed increased confluence of oriented fibrin and platelet aggregates. Monoclonal antibodies directed against different epitopes on the glycoprotein IIb-IIIa complex had varying effects on clot tension development. Monoclonal antibodies A2A9 and 7E3 inhibited clot tension while T10 and 10E5 increased it. Since neither peptides nor antibodies affected the platelet actomyosin ATPase activity, their effect on tension must reflect the interaction between platelets and polymerizing fibrin. We conclude that gamma-400-411 and RGD-peptides increase platelet-polymerizing fibrin interaction. This suggests that clot tension requires a platelet receptor for polymerizing fibrin, which is different from the fibrinogen receptor domain required for aggregation. The results with the monoclonal antibodies support this hypothesis.
Cohen
I
I
Department of Molecular Biology, Northwestern University Medical School, Chicago, IL 60611.
Burk
D L
DL
White
J G
JG
D000911:Antibodies, Monoclonal / Q000502:physiology*; D001666:Binding Sites, Antibody; D001777:Blood Coagulation; D001792:Blood Platelets / Q000201:enzymology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D007552:Isotonic Solutions; D009218:Myosins / Q000097:blood; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D013500:Surface Tension; D013917:Thrombin
D000911:Antibodies, Monoclonal; D005338:Fibrin Fibrinogen Degradation Products; D007552:Isotonic Solutions; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; C046617:arginyl-glycyl-aspartyl-serine; D013917:Thrombin; D009218:Myosins