Fibrinogen Interaction With Platelet Receptors*†

Abstract

In summary: Incubation of platelets with ADP or proteolytic enzymes (chymotrypsin or pronase) results in an exposure of two classes of specific binding sites on platelet surface: low and high affinity fibrinogen receptors. Fibrinogen interaction with these receptors results in platelet aggregation. High affinity fibrinogen receptors are not exposed on thrombasthenic platelets stimulated by ADP but are rendered available on chymotrypsin-treated thrombasthenic platelets; low affinity receptors cannot be exposed by ADP or chymotrypsin on these platelets. Availability of high affinity fibrinogen receptors on thrombasthenic platelets may depend on the residual glycoprotein IIIa. Fibrinogen receptors appear to be associated with glycoproteins IIb, IIIa and a 66,000 Mr platelet membrane component that is exposed during proteolysis of platelet membranes. Some of the platelet-binding sites on the fibrinogen molecule appear to be associated with the COOH-terminal portion of the gamma chain (gamma 374-411). Additional binding sites may also be located in the COOH-terminal portion of the A alpha chain. The conformation of the fibrinogen molecule may be important in its interaction with platelets. Platelet aggregation may result from bridging platelets by fibrinogen molecule in the presence of bivalent cations. In conclusion, platelet interaction with fibrinogen is a complex process involving different binding sites of the fibrinogen molecule. Our own data and review of literature suggest that platelet-interaction with fibrinogen is of major significance in hemostasis.

Interaction between fibrinogen and cultured endothelial cells. Induction of migration and specific binding.

“…Thus, the fg molecule may express interfaces with ECs and may influence EC migration, but direct evidence supporting this concept is still lacking. An attractive hypothesis is that the participation of the molecule in endothelial function is mediated via specific binding sites; the identification of receptor systems for fg on platelets (5,6), macrophages (7,8), and fibroblasts (9,10) may support this concept.…”

Interaction of fibrinogen with its platelet receptor: kinetics and effect of pH and temperature

“…The formation of fibrin from fibrinogen has been the primary focus of studies of the molecule in the hemostatic process, but numerous investigations have documented that fibrinogen also participates in platelet aggregation induced by ADP' [for review, see Mustard & Packham (1970) and Bang et al (1972)l. Only recently has a molecular basis for the role of fibrinogen in platelet aggregation been provided by the demonstration of a direct interaction of the molecule with the cell (Mustard et al, 1978;Marguerie et al, 1979;Bennett & Vilaire, 1979;Niewiarowski et al, 1980;Figures et al, 1980;Peerschke et al, 1980;Harfenist et al, 1980). This interaction involves the binding of fibrinogen to sites on the platelet induced by ADP, and these sites exhibit many of the characteristics of a discrete and saturable receptor system (Marguerie et al, 1979;Bennett & Vilaire, 1979).…”

On the Retraction of Collagen and Fibrin Induced by Normal, Defective and Modified Platelets

“…It is the only one among the examined bleeding syn dromes in which FCR was found to be re duced. The deficiency or anomaly of the GPIIb-GPIIIa complex in thrombasthénie platelets is considered to be responsible for their diminished ability to bind fibrinogen, to aggregate and to retract fibrin [18,22,23]. In contrast, as reported earlier [1] and as con firmed presently, thrombasthénie platelets are as potent in CGR as platelets from healthy subects (table I).…”