BINDING OF FIBRINOGEN TO ADP-TREATED PLATELETS - COMPARISON OF PLASMA-FIBRINOGEN FRACTIONS AND EARLY PLASMIC FIBRINOGEN DERIVATIVES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 101  (3) , 453-460
Abstract
Fibrinogen supports platelet aggregation by binding to specific receptors. The importance of the fibrinogen A.alpha. chain in this hemostatic function is controversial. Fibrinogen derivatives, isolated from plasma or obtained after limited plasmin digestion, apparently lack 13,000-46,000 MW peptides from the carboxyterminal of their A.alpha. 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 Kd 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 A.alpha. chains, was indistinguishable from intact fibrinogen in its ability to bind to platelets and support aggregation. The small differences in binding affinities noted with fractions I-6 and I-9 apparently 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 A.alpha. segments (MW 46,000 to 48,000), as well as aminoterminal segments (B.beta. 1-56) from the B.beta. chains, possessed only 70-75% 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. Fibrinogen binding to platelet receptors apparently does not require the carboxyterminal 2/3 of the A.alpha. chain and low-affinity platelet fibrinogen interactions as revealed by Scatchard analysis reflect fibrinogen binding to platelets via an aminoterminal segment of the A.alpha. and/or B.beta. chains, the loss of which results in a slight but significant decrease in platelet aggregation support.