Role of alpha 2-antiplasmin in fibrin-specific clot lysis with single-chain urokinase-type plasminogen activator in human plasma.
The role of plasma alpha 2-antiplasmin (alpha 2-AP) in the fibrin-specificity of clot lysis by recombinant single-chain urokinase-type plasminogen activator (rscu-PA) and in the conversion of rscu-PA to its two-chain derivative (rtcu-PA, urokinase) was investigated in an in vitro human plasma clot lysis system. Fifty % lysis in 2 h of a 0.1 ml 125I-fibrin labeled human plasma clot immersed in 0.5 ml normal human plasma was obtained with 1.4 +/- 0.15 micrograms/ml rscu-PA (mean +/- SD, n = 8). This was associated with degradation of 23 +/- 7% of fibrinogen and generation of 0.20 +/- 0.09 micrograms/ml rtcu-PA. In alpha 2-AP-depleted plasma 50% clot lysis in 2 h required 2-fold less rscu-PA which was associated with 3-fold more extensive fibrinogen degradation and 2-fold more rtcu-PA generation. Fifty % lysis in 2 h, of a 0.1 ml alpha 2-AP-depleted plasma clot, submersed in 0.5 ml normal plasma, was obtained with 0.80 +/- 0.05 micrograms/ml rscu-PA (n = 3, p less than 0.001 vs normal clot) and was associated with 17 +/- 6% fibrinogen breakdown (p = 0.22 vs normal clot) and 0.08 +/- 0.02 micrograms/ml rtcu-PA generation (p less than 0.05 vs normal clot). In alpha 2-AP-depleted plasma the equipotent rscu-PA concentration was 4-fold lower than in normal plasma and was associated with 3-fold more fibrinogen degradation and a similar extent of rtcu-PA generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Declerck
P J
PJ
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
Lijnen
H R
HR
Verstreken
M
M
Collen
D
D
D005340:Fibrinogen / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D010949:Plasma / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology*; D000979:alpha-2-Antiplasmin / Q000502:physiology*
D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator