Exposure of human platelets to plasmin results in the expression of irreversibly active fibrinogen receptors
Rabhi-Sabile, S.; Pidard, D.
Thrombosis and Haemostasis 73(4): 693-701
1995
ISSN/ISBN: 0340-6245 PMID: 7495081 Document Number: 442915
Although plasmin can trigger strong platelet responses such as shape change and exocytosis of internal granules, limited platelet aggregation is induced by this proteinase, owing to its capacity to rapidly proteolyse secreted adhesive proteins. In this context, we have investigated the state of activation of the fibrinogen receptor, the integrin alpha-IIIb-beta-3, on platelets exposed to plasmin. Following incubation with plasmin at 37 degree C, washing, and resuspension, platelets exhibit a moderate, low-velocity aggregation when stirred in the presence of fibrinogen. Optimum aggregability is observed when platelets have been exposed to plasmin activity of apprxeq 0.5 CU/ml for 20 min, and aggregation is insensitive to the presence of antagonists such as prostaglandin (PG) E-1 and apyrase. Plasmin-induced platelet aggregability is associated with the expression of active fibrinogen receptors on the cell surface, which, using a 125I-fibrinogen binding assay, can be quantified to apprxeq 2,300 molecules per platelet. Exposure of active alpha-IIb-beta-3 receptors appears to depend partially, but not totally on a metabolic activation and granule exocytosis at the time of incubation with plasmin. In contrast with a-thrombin, plasmin-induced activation of alpha-IIb-beta-3 is sustained and cannot be reversed by exposure of platelets to PGE-1. Immunoblotting analysis of the receptor subunits shows no extensive proteolytic modification of alpha-IIb-beta-3 by plasmin, and only reveals a limited proteolysis of the aminoterminal domain of the alpha-IIb subunit. In addition to their capacity to aggregate in the presence of fibrinogen alone, plasmin-treated platelets also show a potentiated aggregability in response to low doses of ADP. Thus, plasmin has the potential to activate the platelet fibrinogen receptor in such a way that it remains irreversibly available to fibrinogen on the surface of nonaggregated cells, a feature that may participate to pathological states of in vivo platelet hyperaggregability.