Reciprocating autocatalytic interactions between platelets and the activation system.
Under normal circumstances, the platelet surface serves as a site of assembly for plasminogen (PGN) and tissue-type plasminogen activator (t-PA) and facilitates PGN activation. Since the plasmin (Pn) produced on the platelet surface can modulate a variety of platelet properties, we examined the effects of Pn on platelet-surface PGN activation. We incubated platelets with Pn (one caseinolytic unit/ml for one hr at 37 degrees C) and measured the effects of this treatment on the binding of PGN, Pn, and t-PA to unactivated platelets; and on the kinetics of PGN activation on the platelet surface. Pn treatment increased the number of PGN binding sites by 78% (from 46,000 to 88,000 sites/platelet) without affecting affinity (KD = 2.2 microM). Pn treatment had a modest effect on (DFP-inactivated) Pn binding but did not modify t-PA binding; however, treatment increased the catalytic efficiency of t-PA approximately two-fold. Importantly, all of these effects occurred without evidence for platelet activation by Pn. These observations imply that PGN activation may be an autocatalytic process on the platelet surface and provide evidence for a unique reciprocating mechanism governing the interaction between platelets and the plasminogen activation system.
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
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Ouimet
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Loscalzo
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002384:Catalysis; D005341:Fibrinolysin / Q000494:pharmacology*; D006801:Humans; D010958:Plasminogen / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014148:Tranexamic Acid / Q000494:pharmacology
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014148:Tranexamic Acid; D010958:Plasminogen; C067262:PLAT protein, human; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin