Increased Yield of Human Tissue-Type Plasminogen Activator Obtained by Means of Recombinant DNA Technology

1985 ◽  
Vol 54 (02) ◽  
pp. 422-424 ◽  
Author(s):  
M J Browne ◽  
I Dodd ◽  
J E Carey ◽  
C G Chapman ◽  
J H Robinson
Keyword(s):  
Cell Line ◽  
Plasminogen Activator ◽  
Human Tissue ◽  
Recombinant Dna ◽  
Sodium Dodecyl ◽  
Tissue Type ◽  
Parent Cell ◽  
Recombinant Dna Technology ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryExtra copies of the human tissue-type plasminogen activator (t-PA) gene were introduced into the Bowes melanoma cell line. We obtained a recombinant cell line (TRBM6) which secretes approximately ten-fold more t-PA than the parent cell line. The identity of the plasminogen activator made by the new cell line was confirmed by sizing on sodium dodecyl sulphate polyacrylamide gels and by specific quenching using anti-t-PA antibody. We estimate that the recombinant line produces t-PA at a rate of approximately 3 pg/cell/24 hr and that t-PA accumulates in the harvest medium at a rate of approximately 4000 International t-PA Units/ml/24 hr.

scholarly journals Influence of fibrin and liver blood flow on the turnover and the systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator in rabbits

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1493-1497 ◽  
Author(s):  
H Bounameaux ◽  
JM Stassen ◽  
C Seghers ◽  
D Collen
Keyword(s):  
Blood Flow ◽  
Plasminogen Activator ◽  
Human Tissue ◽  
Femoral Vein ◽  
Liver Blood Flow ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Cardiovascular Failure ◽  
Type Plasminogen Activator ◽  
Impaired Liver

Abstract The influence of the presence of fibrin microclots on the systemic fibrinogenolytic effects of intravenous (IV) recombinant human tissue- type plasminogen activator (rt-PA) was studied by injection of a homogenized fibrin suspension in the femoral vein or artery in rabbits. A linear correlation (P less than .001) was found between the extent of fibrinogen breakdown and the amount of fibrin (0 to 32 mg/kg) injected just prior to the IV infusion of rt-PA at a rate of 10 micrograms/kg/min for 60 minutes. This finding suggests that the systemic activation of the fibrinolytic system observed in some patients during infusion of rt-PA may be due, at least in part, to the presence of fibrin in the vascular bed. The effect of blood flow in the liver on the turnover of rt-PA was measured in rabbits after ligation of the hepatic artery and monitoring of the blood flow in the portal vein with a peristaltic pump. The half-life (t1/2) of rt-PA in plasma was inversely correlated with the logarithm of the rate of the liver blood flow. A doubling of the plasma t1/2 of rt-PA was observed after an eightfold reduction of the liver blood flow, suggesting that delayed clearance of rt-PA may occur in patients with severe cardiovascular failure and impaired liver blood flow.

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