Kinetics and mechanism of platelet-surface plasminogen activation by tissue-type plasminogen activator.
Plasminogen and tissue-type plasminogen activator bind to the platelet surface, and as a result, the catalytic efficiency of plasminogen activation is significantly enhanced. The plasmin that is generated on or near the platelet is known to affect a number of platelet surface events. For this reason, we examined the effect of plasmin on platelet-surface plasminogen activation and its determinants. Specifically, we measured the effects of plasmin treatment of platelets (1 caseinolytic unit/mL for 1 h at 37 degrees C) on plasminogen, tissue-type plasminogen activator, and plasmin binding to the unactivated and ADP-activated platelet surface; and on the kinetics of plasminogen activation on the platelet surface. Following plasmin treatment, the number of plasminogen binding sites on unactivated platelets increased by 78% (from 46,000 +/- 4000 to 88,000 +/- 9000 sites/platelet), while the number of tissue-type plasminogen activator sites did not change, and the number of diisopropyl fluorophosphate (DFP)-inactivated plasmin (DFP-plasmin) binding sites decreased by 31% (from 92,000 +/- 11,000 to 65,000 +/- 7000 sites/platelet); the dissociation constants (Kds) for each of these binding processes did not change significantly following treatment. On ADP-activated platelets, plasmin treatment increased the number of plasminogen binding sites by 41% (from 188,000 +/- 17,000 to 265,000 +/- 25,000 sites/platelet), decreased the number of plasmin binding sites by 28% (from 219,000 +/- 41,000 to 157,000 +/- 24,000 sites/platelet), and did not affect the number of tissue-type plasminogen activator sites; again, the Kds for each of these binding processes did not change significantly following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Ouimet
H
H
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Freedman
J E
JE
Loscalzo
J
J
D001667:Binding, Competitive; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D002850:Chromatography, Gel; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D010958:Plasminogen / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin