Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca2+.
The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with 125I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37 degrees C in the absence of exogenous Ca2+, conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca2+. The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation.
Winters
K J
KJ
Cardiovascular Division, Washington University School of Medicine, St Louis MO 63110.
Eisenberg
P R
PR
Jaffe
A S
AS
Santoro
S A
SA
D000911:Antibodies, Monoclonal; D002118:Calcium / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005341:Fibrinolysin / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007457:Iodine Radioisotopes; D010958:Plasminogen / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D038981:Receptors, Collagen; D013300:Streptokinase / Q000494:pharmacology; D013696:Temperature; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; C028254:von Willebrand factor receptor; D010958:Plasminogen; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D002118:Calcium