Role of Platelet Fibrinogen in the Reactions of Platelets to Thrombin*

Abstract

Washed human blood platelets contain a clottable protein that is similar to, if not identical with, plasma fibrinogen (1-4). After incubation with trypsin under appropriate conditions, platelets remain morphologically intact but no longer contain clottable protein (5). Trypsinized platelets, unlike normal platelets, are not aggregated by fresh serum or by a solution of thrombin and calcium chloride. When resuspended in plateletfree plasma or in a buffered solution of fibrinogen containing glucose, trypsinized platelets produce retraction of clots formed by thrombin; during the formation of the clot and its subsequent retraction, trypsinized platelets aggregate and undergo the usual changes of viscous metamorphosis (5). These observations suggest that fibrinogen on the surface of platelets is involved in the reaction of platelets to thrombin. This reaction does not consist simply of the coagulation of fibrinogen with entrapment of platelets in the fibrin mesh. Under usual conditions divalent cations are required for thrombin-induced platelet aggregation but not for clotting of fibrinogen (5, 6). Electron photomicrographs of platelet aggregates show no striated fibrin strands between adherent

The stimulation by thrombin of glucose oxidation in human platelets.

“…The value for the radioactivity of these control specimens, about 100 cpm per 109 platelets, was subtracted from the value of each experimental result. 3 4 All determinations were performed in duplicate.…”

“…Thrombin, a proteolytic enzyme, is believed to cleave a fibrinogen-like constituent of the platelet membrane (4,5). This change in the platelet membrane renders it more permeable to serotonin, ADP, protein, and ions such as potassium and calcium (33,36), but the increased permeability may be relatively specific, since quite different proportions of various intracellular substances escape (33).…”

“…Thrombin, possibly by cleaving fibrinogen in the plasma membrane of the platelet (4,5), produces a morphologic change in the membrane (6) and causes platelets to become adherent and aggregate; in the midst of a clot they fasten to fibrin strands (7). It has been suggested that retraction of the fibrin clot is effected by thrombosthenin, an actomyosinlike contractile protein of platelets (8).…”

A method for investigating the role of calcium in the shape change, aggregation and serotonin release of rat platelets.

“…Although platelets are capable of high affinity uptake and stimulus-coupled secretion of serotonin, they have received little attention as a model secretary system because numerous studies have concluded that serotonin release by platelets is not dependent on extracellular Ca2+ and that intracellular stores provide what Ca2+ is needed for this purpose. In particular, thrombin (Morse, Jackson & Conley, 1965;Miller, Katz & Feinstein, 1975) and the Ca2+ ionophore A23187 (Massini & Luscher, 1974;White, Rao & Gerrard, 1974;Feinman & Detwiler, 1974;Feinstein & Fraser, 1975) both induce release by platelets incubated in a Ca2+-depleted medium (with added EDTA or EGTA), and this common observation has been used to support the above contention. While we have presented no evidence to refute the idea that a sarcoplasmic-reticulum-like organelle might function in platelets to provide Ca2+ for intracellular physiology and metabolism, we would suggest that the role of such an organelle may have been over-estimated and that given the appropriate circumstances, platelets do possess a release system which has a stringent requirement for extracellular Ca2+.…”

Plasminogen interacts with human platelets through two distinct mechanisms.

“…Interaction of plasminogen with platelets provides one mechanism by which platelets might participate in fibrinolysis. Early evidence in the literature suggested this possibility (1,3). We have recently demonstrated specific and saturable binding of plasminogen to platelets (4).…”