Pro-urokinase and prekallikrein are both associated with platelets. Implications for the intrinsic pathway of fibrinolysis and for therapeutic thrombolysis.
The contact-dependent intrinsic pathway of fibrinolysis involving factor XII, prekallikrein (PK) and pro-urokinase (pro-UK) remains poorly understood. Casein autography of washed, intact platelets revealed both PK and pro-UK. Accordingly, platelets may mediate physiological thrombolysis by this pathway since factor XIIa activates PK and kallikrein activates pro-UK. Acid washing dissociated PK but not pro-UK from platelets. Exogenous pro-UK was specifically incorporated by platelets from the ambient fluid and similarly could not be dissociated from intact platelets. Therefore, platelets may also mediate an effect from therapeutically administered pro-UK by prolonging its half-life.
Gurewich
V
V
Vascular Research Laboratory, Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
Johnstone
M
M
Loza
J P
JP
Pannell
R
R
D001792:Blood Platelets / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D015956:Factor XIIa / Q000494:pharmacology; D005342:Fibrinolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007610:Kallikreins / Q000494:pharmacology; D011288:Prekallikrein / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000097:blood; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood*
D011994:Recombinant Proteins; D011288:Prekallikrein; D007610:Kallikreins; D015956:Factor XIIa; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase