Binding of fibrinogen to ADP-treated platelets. Comparison of plasma fibrinogen fractions and early plasmic fibrinogen derivatives

Ellinor I.B. Peerschke, Dennis K. Galanakis

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Fibrinogen supports platelet aggregation by binding to specific receptors. The importance of the fibrinogen Aα chain in this hemostatic function is controversial. We found that fibrinogen derivatives, isolated from plasma or obtained after limited plasmin digestion, that lacked approximately 13,000 to 46,000 MW peptides from the carboxyterminal of their Aα chains (I-6, I-9, I-9D88) displayed undiminished capacity to support ADP-induced platelet aggregation and to bind to gel-filtered platelets. Analysis of their binding disclosed upwardly concave Scatchard plots that could be resolved into high- and low-affinity binding components similar to those of intact fibrinogen. The dissociation constant for high-affinity binding of fractions I-6 and I-9, however, was slightly higher than that of intact fibrinogen, correlating with the slight decrease in the rate of platelet aggregation observed using these fractions. Low-affinity binding was unchanged. In contrast, fibrinogen derivative I-9D88, lacking as much as 2 3 from the carboxyterminal side of both Aα chains, was indistinguishable from intact fibrinogen in its ability to bind to platelets and support aggregation. This suggested that the small differences in binding affinities noted with fractions I-6 and I-9 were most likely due to changes in molecular conformation rather than to losses of specific peptides. A more degraded derivative (I-9D50) lacking even larger Aα segments (MW 46,000 to 48,000), as well as aminoterminal segments (Bβ I-56) from the Bβ chains, possessed only 70% to 75% of the platelet aggregating activity of intact fibrinogen. Its binding to ADP-treated platelets was quantitatively similar to that of intact fibrinogen but its Scatchard plot was linear, with loss of low-affinity binding. These data indicate that (1) fibrinogen binding to platelet receptors does not require the carboxyterminal 2 3 of the Aα chain and (2) low-affinity platelet fibrinogen interactions as revealed by Scatchard analysis reflect fibrinogen binding to platelets via an aminoterminal segment of the Aα and/or Bβ chains, the loss of which results in a slight but significant decrease in platelet aggregation support.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalTranslational Research
Volume101
Issue number3
StatePublished - Mar 1983
Externally publishedYes

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