Binding of human tissue plasminogen activator (t-PA) to blood clots and clot-lytic activity of clot-bound t-PA.
The binding affinity; incorporation and adsorption, of human tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) for blood clots was investigated in vitro. In order to study the incorporation, the blood clot formation was performed after mixing [125I]t-PA or [125I]u-PA with the blood obtained from human and several animal species. The radioactivities of [125I]t-PA incorporated in blood clots of human, dog, rat and rabbit were higher than those of [125I]u-PA. The adsorption study was carried out by immersing the blood clot in saline containing the [125I]plasminogen activators (PAs). The adsorptions of [125I]t-PA to blood clots of human and animals were higher than those of [125I]u-PA. The results suggest that t-PA has a much higher affinity for fibrin in blood clots than u-PA. The blood clot lysis caused by the clot-bound PAs was investigated using the [125I]fibrin-containing blood clots pretreated with t-PA or u-PA. In the human blood clot, the clot-bound t-PA showed a dose-dependent clot lysis at the concentrations of t-PA ranging from 0.3 to 3 nM, while the clot-bound u-PA has little clot-lytic activity. The t-PA bound to the human blood clot showed the most effective clot lysis as compared with those bound to the animal blood clots.
Kimata
H
H
Tokyo Research Laboratories, Kowa Co., Ltd., Japan.
Nakajima
K
K
Yamamoto
S
S
Hasegawa
A
A
D000327:Adsorption; D000818:Animals; D004285:Dogs; D005343:Fibrinolytic Agents / Q000097:blood; D006801:Humans; D010960:Plasminogen Activators / Q000097:blood; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood*; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
D005343:Fibrinolytic Agents; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator