Irreversible platelet fibrinogen interactions occur independently of fibrinogen alpha chain degradation and are not mediated by intact platelet membrane glycoprotein IIb-IIIa complexes.
Interactions between fibrinogen and human platelets leading to irreversible fibrinogen binding are poorly understood. Because fibrinogen possesses platelet recognition sites on both its alpha and gamma chains, the present study examined the hypothesis that irreversible platelet fibrinogen interactions occurred as a result of multivalent fibrinogen binding to platelet membrane glycoprotein IIb-IIIa complexes. Fibrinogen binding to human, gel-filtered platelets was assessed by using intact fibrinogen and a plasmic fibrinogen degradation product (8D-50) lacking intact alpha chains and resembling an intermediate fragment X. Irreversibly bound fibrinogen was defined as fibrinogen that remained associated with thrombin-stimulated platelets in the presence of 10 mmol/L ethylenediaminetetraacetic acid (EDTA) or excess unlabeled fibrinogen. The amount of intact fibrinogen that bound irreversibly to platelets comprised 54% +/- 12% (mean +/- SD, n = 8) of total binding. It was unaffected by fibrinogen receptor saturation and platelet alpha granule release. Similar amounts of 8D-50 (56% +/- 10%) bound irreversibly to platelets. Addition of 50 mumol/L arginine-glycine-asparagine-serine, after the initial binding of either fibrinogen or 8D-50, had no effect on the subsequent stabilization of platelet-fibrinogen or platelet-8D-50 interactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Peerschke
E I
EI
Department of Pathology, State University of New York, Stony Brook 11794.
D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D002648:Child; D004347:Drug Interactions; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D010979:Platelet Function Tests; D010980:Platelet Membrane Glycoproteins / Q000494:pharmacology*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000032:analysis*; D018000:Receptors, Peptide
D005338:Fibrin Fibrinogen Degradation Products; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C048650:fibrin-fibrinogen degradation products receptor; D005340:Fibrinogen